Conference Coverage

There were no significant differences in COVID-19 outcomes between cases caught by routine screening and screening based on symptoms/exposure history among cancer outpatients treated at Mayo Clinic facilities, according to a review of 224 cases.

The finding led to a shift away from routine COVID-19 screening to screening based on symptoms and exposures, said lead investigator Zhuoer Xie, MD, a hematology/oncology fellow at Mayo’s Rochester, Minn., campus.

“We are so happy” to see these results and be able to move away from routine screening. It’s burdensome and uncomfortable for patients and expensive to administer, Dr. Xie said at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S06-03).

Also, “our results provide reassurance that cancer care may safely continue during the pandemic with appropriate precautions,” she said.

Like many institutions, Mayo instituted routine COVID-19 screening for cancer outpatients at the start of the pandemic, requiring patients be tested 24 hours before systemic treatment, radiation therapy, or surgery. People on multiday regimens were screened twice a week.

Among 5,452 patients at the Rochester campus and its surrounding satellites, plus Mayo’s facilities in Phoenix and Jacksonville, Fla., routine screening picked up 63 COVID-19 cases (1.2%) from March 18 to July 31, 2020.

The outcomes were compared with 161 COVID-19 cases screened due to symptoms and exposure history. Most of the patients were on cancer surveillance as opposed to active treatment with routine testing.

Overall, 17.5% of cases caught by routine screening (11/63) were hospitalized versus 26.7% of patients screened for risk factors (43/161).

There was one COVID-19-related ICU admission among the 63 routine screening cases (1.6%) and nine ICU admissions (5.6%) among the risk-factor screening group. Three people diagnosed by routine screening (4.8%) died, compared with six deaths in the risk factor screening group (3.7%). The differences were not statistically significant, and there was no difference in treatment delay based on screening method.

The mortality rate was substantially lower than previously reported for COVID-19 among cancer patients, perhaps in part because Mayo facilities were not overwhelmed with cases early in the pandemic, so there was never a shortage of hospital beds and other resources, Dr. Xie said.

“Many of us are glad to see your data. It’s comforting,” said presentation moderator Solange Peters, MD, PhD, head of medical oncology at the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

With proper precautions, “we can firmly encourage patients to come” in for their “cancer treatment without any hesitation,” Dr. Peters said.

“We feel the same way. We tell our patients this might be the safest place for you to be. Everybody is masked; everybody is taking all the precautions,” said Sheena Bhalla, MD, a hematology/oncology fellow as the Icahn School of Medicine at Mount Sinai, New York.

“We are [also] reaching out to patients who have been hesitant” about the COVID-19 vaccine, Dr. Bhalla said, “and trying to get them vaccinated. We are still learning how cancer patients will do with the vaccine, but we think that some protection is better than no protection.”

Currently at Mayo’s main campus in Rochester and its surrounding clinics, COVID-19 screening is based on symptoms, exposure, and factors such as high risk for neutropenic fever.

Mayo’s Arizona and Florida campuses had a surge of cases a few months ago, so routine screening is still used there but only on a monthly basis for people on active treatment.

Consistent with previous reports, older age and lymphopenia increased the risk of COVID-19 hospitalization in Mayo’s study, but comorbidities and active cancer treatment did not.

COVID-19 patients were a median of 62 years old, and 42% were women. Breast, genitourinary, and gastrointestinal tumors were the most common cancers.

Respiratory failure and sepsis were the most common complications among the 54 hospital admissions; eight patients required intubation.

The funding source wasn’t reported. The speakers had no relevant disclosures.

aotto@mdedge.com

There were no significant differences in COVID-19 outcomes between cases caught by routine screening and screening based on symptoms/exposure history among cancer outpatients treated at Mayo Clinic facilities, according to a review of 224 cases.

The finding led to a shift away from routine COVID-19 screening to screening based on symptoms and exposures, said lead investigator Zhuoer Xie, MD, a hematology/oncology fellow at Mayo’s Rochester, Minn., campus.

“We are so happy” to see these results and be able to move away from routine screening. It’s burdensome and uncomfortable for patients and expensive to administer, Dr. Xie said at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S06-03).

Also, “our results provide reassurance that cancer care may safely continue during the pandemic with appropriate precautions,” she said.

Like many institutions, Mayo instituted routine COVID-19 screening for cancer outpatients at the start of the pandemic, requiring patients be tested 24 hours before systemic treatment, radiation therapy, or surgery. People on multiday regimens were screened twice a week.

Among 5,452 patients at the Rochester campus and its surrounding satellites, plus Mayo’s facilities in Phoenix and Jacksonville, Fla., routine screening picked up 63 COVID-19 cases (1.2%) from March 18 to July 31, 2020.

The outcomes were compared with 161 COVID-19 cases screened due to symptoms and exposure history. Most of the patients were on cancer surveillance as opposed to active treatment with routine testing.

Overall, 17.5% of cases caught by routine screening (11/63) were hospitalized versus 26.7% of patients screened for risk factors (43/161).

There was one COVID-19-related ICU admission among the 63 routine screening cases (1.6%) and nine ICU admissions (5.6%) among the risk-factor screening group. Three people diagnosed by routine screening (4.8%) died, compared with six deaths in the risk factor screening group (3.7%). The differences were not statistically significant, and there was no difference in treatment delay based on screening method.

The mortality rate was substantially lower than previously reported for COVID-19 among cancer patients, perhaps in part because Mayo facilities were not overwhelmed with cases early in the pandemic, so there was never a shortage of hospital beds and other resources, Dr. Xie said.

“Many of us are glad to see your data. It’s comforting,” said presentation moderator Solange Peters, MD, PhD, head of medical oncology at the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

With proper precautions, “we can firmly encourage patients to come” in for their “cancer treatment without any hesitation,” Dr. Peters said.

“We feel the same way. We tell our patients this might be the safest place for you to be. Everybody is masked; everybody is taking all the precautions,” said Sheena Bhalla, MD, a hematology/oncology fellow as the Icahn School of Medicine at Mount Sinai, New York.

“We are [also] reaching out to patients who have been hesitant” about the COVID-19 vaccine, Dr. Bhalla said, “and trying to get them vaccinated. We are still learning how cancer patients will do with the vaccine, but we think that some protection is better than no protection.”

Currently at Mayo’s main campus in Rochester and its surrounding clinics, COVID-19 screening is based on symptoms, exposure, and factors such as high risk for neutropenic fever.

Mayo’s Arizona and Florida campuses had a surge of cases a few months ago, so routine screening is still used there but only on a monthly basis for people on active treatment.

Consistent with previous reports, older age and lymphopenia increased the risk of COVID-19 hospitalization in Mayo’s study, but comorbidities and active cancer treatment did not.

COVID-19 patients were a median of 62 years old, and 42% were women. Breast, genitourinary, and gastrointestinal tumors were the most common cancers.

Respiratory failure and sepsis were the most common complications among the 54 hospital admissions; eight patients required intubation.

The funding source wasn’t reported. The speakers had no relevant disclosures.

aotto@mdedge.com

There were no significant differences in COVID-19 outcomes between cases caught by routine screening and screening based on symptoms/exposure history among cancer outpatients treated at Mayo Clinic facilities, according to a review of 224 cases.

The finding led to a shift away from routine COVID-19 screening to screening based on symptoms and exposures, said lead investigator Zhuoer Xie, MD, a hematology/oncology fellow at Mayo’s Rochester, Minn., campus.

“We are so happy” to see these results and be able to move away from routine screening. It’s burdensome and uncomfortable for patients and expensive to administer, Dr. Xie said at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S06-03).

Also, “our results provide reassurance that cancer care may safely continue during the pandemic with appropriate precautions,” she said.

Like many institutions, Mayo instituted routine COVID-19 screening for cancer outpatients at the start of the pandemic, requiring patients be tested 24 hours before systemic treatment, radiation therapy, or surgery. People on multiday regimens were screened twice a week.

Among 5,452 patients at the Rochester campus and its surrounding satellites, plus Mayo’s facilities in Phoenix and Jacksonville, Fla., routine screening picked up 63 COVID-19 cases (1.2%) from March 18 to July 31, 2020.

The outcomes were compared with 161 COVID-19 cases screened due to symptoms and exposure history. Most of the patients were on cancer surveillance as opposed to active treatment with routine testing.

Overall, 17.5% of cases caught by routine screening (11/63) were hospitalized versus 26.7% of patients screened for risk factors (43/161).

There was one COVID-19-related ICU admission among the 63 routine screening cases (1.6%) and nine ICU admissions (5.6%) among the risk-factor screening group. Three people diagnosed by routine screening (4.8%) died, compared with six deaths in the risk factor screening group (3.7%). The differences were not statistically significant, and there was no difference in treatment delay based on screening method.

The mortality rate was substantially lower than previously reported for COVID-19 among cancer patients, perhaps in part because Mayo facilities were not overwhelmed with cases early in the pandemic, so there was never a shortage of hospital beds and other resources, Dr. Xie said.

“Many of us are glad to see your data. It’s comforting,” said presentation moderator Solange Peters, MD, PhD, head of medical oncology at the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

With proper precautions, “we can firmly encourage patients to come” in for their “cancer treatment without any hesitation,” Dr. Peters said.

“We feel the same way. We tell our patients this might be the safest place for you to be. Everybody is masked; everybody is taking all the precautions,” said Sheena Bhalla, MD, a hematology/oncology fellow as the Icahn School of Medicine at Mount Sinai, New York.

“We are [also] reaching out to patients who have been hesitant” about the COVID-19 vaccine, Dr. Bhalla said, “and trying to get them vaccinated. We are still learning how cancer patients will do with the vaccine, but we think that some protection is better than no protection.”

Currently at Mayo’s main campus in Rochester and its surrounding clinics, COVID-19 screening is based on symptoms, exposure, and factors such as high risk for neutropenic fever.

Mayo’s Arizona and Florida campuses had a surge of cases a few months ago, so routine screening is still used there but only on a monthly basis for people on active treatment.

Consistent with previous reports, older age and lymphopenia increased the risk of COVID-19 hospitalization in Mayo’s study, but comorbidities and active cancer treatment did not.

COVID-19 patients were a median of 62 years old, and 42% were women. Breast, genitourinary, and gastrointestinal tumors were the most common cancers.

Respiratory failure and sepsis were the most common complications among the 54 hospital admissions; eight patients required intubation.

The funding source wasn’t reported. The speakers had no relevant disclosures.

aotto@mdedge.com

When cases of COVID-19 began to surge in New York City in March 2020, Carol A. Bernstein, MD, did her best to practice psychiatry and carry out administrative tasks from a home office, but by mid-May, she became stir-crazy.

Courtesy Dr. Carol A. Bernstein

“I just couldn’t stand it, anymore,” Dr. Bernstein said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “I came back to work at least just to see my colleagues, because I felt so disconnected. Normally, in a disaster, people come together – whether it’s responding to an earthquake or a fire or whatever. People come together to provide themselves with support. They hug each other and hold each other’s hands. We could not and cannot do that in this pandemic.”

According to Dr. Bernstein, stress, fear, and uncertainty triggered by the COVID-19 pandemic require special attention to the needs of health care personnel.

“Taking care of yourself and encouraging others to do the same sustains the ability to care for those in need,” said Dr. Bernstein, who is vice chair for faculty development and well-being in the departments of psychiatry and behavioral science and obstetrics and gynecology at Montefiore Medical Center/Albert Einstein College of Medicine, New York. “This includes both meeting practical needs as well as physical and emotional self-care. Everyone is impacted by this, so emotional support needs to be available to everyone. In the psychiatric community, we have triple challenges. We have to take care of our patients, our colleagues, and ourselves. It’s a lot.”

Specific challenges for health care workers include the potential for a surge in care demand and uncertainty about future outbreaks.

“Although we don’t have [personal protective] and respirator shortages at the moment, we’re worried about the vaccine shortages,” she said. Then there’s the fact that patients with comorbid conditions have the highest risk of death and the task of providing supportive care as well as medical care. “Of course, we still have a risk of becoming infected or infecting our families. There is additional psychological stress: fear, grief, frustration, guilt, insomnia, and exhaustion.”

Now, more than a year removed from the start of the pandemic, health care personnel are experiencing compassion fatigue, which she described as the inability to feel compassion for our patients because of our inability to feel compassion for ourselves. “We’re certainly experiencing burnout, although the primary aspect of burnout that we are experiencing is emotional exhaustion,” said Dr. Bernstein, who also is a past president of the American Psychiatric Association.

General risk factors for burnout and distress include sleep deprivation, high levels of work/life conflict, work interrupted by personal concerns, high levels of anger, loneliness, or anxiety, the stress of work relationships/work outcomes, anxiety about competency, difficulty “unplugging” after work, and regular use of alcohol and other drugs. At the same time, she continued, signs of burnout and secondary traumatic stress include sadness, depression, or apathy; feeling easily frustrated; feeling isolated and disconnected from others; excessive worry or fear about something bad happening; feeling like a failure, and feeling tired, exhausted, or overwhelmed.

“Why is this crisis so hard for us docs?” she asked. “Because focusing on ourselves – with worries like ‘are we okay? Are we going to get sick?’ – compromises our focus on patients. This can lead to medical errors and unprofessional behavior. There are significant feelings of guilt that ‘I’m not doing enough.’

“This was true for a lot of us in psychiatry who were working virtually early during the pandemic while our medicine colleagues were on the front lines exposing themselves to COVID. Even the people working on the COVID units at the height on the initial surge felt guilty because treatment algorithms were changing almost every day. Fortunately, protocols are more established now, but the sense of not doing enough is pervasive and makes it difficult for us to ask for help.”

Fear of the unknown also posed a challenge to the workforce. “We didn’t know what we were dealing with at first,” she said. “The loss of control and autonomy, which is a major driver of burnout in the best of circumstances, was particularly true here in New York. People were told what to do. They were deployed into new circumstances. We experienced a significant loss of control, both of the virus and of what we were doing, and a widespread sense of isolation and loneliness.”

To cultivate resilience going forward, Dr. Bernstein advocates for the concept of psychological flexibility, which she defined as the ability to stay in contact with the present moment regardless of unpleasant thoughts, feelings, and bodily sensations, while choosing one’s behaviors based on the situation and personal values. “It is understanding that you can feel demoralized and bad one minute and better the next day,” she said. “This is a key concept for being able to continuously adapt under stressful circumstances and to tolerate uncertainty.”

She advises clinicians to identify safe areas and behaviors, and to maximize their ability to care for themselves and their families – including keeping in touch with colleagues and people you care about. “You also want to take advantage of calming skills and the maintenance of natural body rhythms,” she said. “This includes sensible nutrition and getting adequate rest and exercise.”

Dr. Bernstein also emphasized the importance of trying to maintain hope and optimism while not denying risk. “We also have to think about ethics, to provide the best possible care given the circumstances,” she said. “The crisis standards of care are necessarily different. We are not ethically required to offer futile care, but we must tell the truth.”

She pointed out that resilience is sometimes thought of as returning to the way you were before a stressful or life-altering event. “But here we refer to it as using your coping resources, connecting to others, and cultivating your values and purpose in life as you ride through this time of stress,” Dr. Bernstein said. “You are aware of the time it takes to develop and test for treatment and vaccine efficacy, and to then roll out these interventions, so you do know there will be an end to this, hopefully by the summer. While you won’t forget this time, focus on what you can control, your positive relationships, remind yourself of your purpose, and practice gratitude for what you are thankful for in your life. We need to cultivate what is positive and promote the message that emotional health should have the same priority level as physical health. The goal is to flourish.”

Dr. Bernstein reported having no financial disclosures.

dbrunk@mdedge.com

When cases of COVID-19 began to surge in New York City in March 2020, Carol A. Bernstein, MD, did her best to practice psychiatry and carry out administrative tasks from a home office, but by mid-May, she became stir-crazy.

Courtesy Dr. Carol A. Bernstein

“I just couldn’t stand it, anymore,” Dr. Bernstein said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “I came back to work at least just to see my colleagues, because I felt so disconnected. Normally, in a disaster, people come together – whether it’s responding to an earthquake or a fire or whatever. People come together to provide themselves with support. They hug each other and hold each other’s hands. We could not and cannot do that in this pandemic.”

According to Dr. Bernstein, stress, fear, and uncertainty triggered by the COVID-19 pandemic require special attention to the needs of health care personnel.

“Taking care of yourself and encouraging others to do the same sustains the ability to care for those in need,” said Dr. Bernstein, who is vice chair for faculty development and well-being in the departments of psychiatry and behavioral science and obstetrics and gynecology at Montefiore Medical Center/Albert Einstein College of Medicine, New York. “This includes both meeting practical needs as well as physical and emotional self-care. Everyone is impacted by this, so emotional support needs to be available to everyone. In the psychiatric community, we have triple challenges. We have to take care of our patients, our colleagues, and ourselves. It’s a lot.”

Specific challenges for health care workers include the potential for a surge in care demand and uncertainty about future outbreaks.

“Although we don’t have [personal protective] and respirator shortages at the moment, we’re worried about the vaccine shortages,” she said. Then there’s the fact that patients with comorbid conditions have the highest risk of death and the task of providing supportive care as well as medical care. “Of course, we still have a risk of becoming infected or infecting our families. There is additional psychological stress: fear, grief, frustration, guilt, insomnia, and exhaustion.”

Now, more than a year removed from the start of the pandemic, health care personnel are experiencing compassion fatigue, which she described as the inability to feel compassion for our patients because of our inability to feel compassion for ourselves. “We’re certainly experiencing burnout, although the primary aspect of burnout that we are experiencing is emotional exhaustion,” said Dr. Bernstein, who also is a past president of the American Psychiatric Association.

General risk factors for burnout and distress include sleep deprivation, high levels of work/life conflict, work interrupted by personal concerns, high levels of anger, loneliness, or anxiety, the stress of work relationships/work outcomes, anxiety about competency, difficulty “unplugging” after work, and regular use of alcohol and other drugs. At the same time, she continued, signs of burnout and secondary traumatic stress include sadness, depression, or apathy; feeling easily frustrated; feeling isolated and disconnected from others; excessive worry or fear about something bad happening; feeling like a failure, and feeling tired, exhausted, or overwhelmed.

“Why is this crisis so hard for us docs?” she asked. “Because focusing on ourselves – with worries like ‘are we okay? Are we going to get sick?’ – compromises our focus on patients. This can lead to medical errors and unprofessional behavior. There are significant feelings of guilt that ‘I’m not doing enough.’

“This was true for a lot of us in psychiatry who were working virtually early during the pandemic while our medicine colleagues were on the front lines exposing themselves to COVID. Even the people working on the COVID units at the height on the initial surge felt guilty because treatment algorithms were changing almost every day. Fortunately, protocols are more established now, but the sense of not doing enough is pervasive and makes it difficult for us to ask for help.”

Fear of the unknown also posed a challenge to the workforce. “We didn’t know what we were dealing with at first,” she said. “The loss of control and autonomy, which is a major driver of burnout in the best of circumstances, was particularly true here in New York. People were told what to do. They were deployed into new circumstances. We experienced a significant loss of control, both of the virus and of what we were doing, and a widespread sense of isolation and loneliness.”

To cultivate resilience going forward, Dr. Bernstein advocates for the concept of psychological flexibility, which she defined as the ability to stay in contact with the present moment regardless of unpleasant thoughts, feelings, and bodily sensations, while choosing one’s behaviors based on the situation and personal values. “It is understanding that you can feel demoralized and bad one minute and better the next day,” she said. “This is a key concept for being able to continuously adapt under stressful circumstances and to tolerate uncertainty.”

She advises clinicians to identify safe areas and behaviors, and to maximize their ability to care for themselves and their families – including keeping in touch with colleagues and people you care about. “You also want to take advantage of calming skills and the maintenance of natural body rhythms,” she said. “This includes sensible nutrition and getting adequate rest and exercise.”

Dr. Bernstein also emphasized the importance of trying to maintain hope and optimism while not denying risk. “We also have to think about ethics, to provide the best possible care given the circumstances,” she said. “The crisis standards of care are necessarily different. We are not ethically required to offer futile care, but we must tell the truth.”

She pointed out that resilience is sometimes thought of as returning to the way you were before a stressful or life-altering event. “But here we refer to it as using your coping resources, connecting to others, and cultivating your values and purpose in life as you ride through this time of stress,” Dr. Bernstein said. “You are aware of the time it takes to develop and test for treatment and vaccine efficacy, and to then roll out these interventions, so you do know there will be an end to this, hopefully by the summer. While you won’t forget this time, focus on what you can control, your positive relationships, remind yourself of your purpose, and practice gratitude for what you are thankful for in your life. We need to cultivate what is positive and promote the message that emotional health should have the same priority level as physical health. The goal is to flourish.”

Dr. Bernstein reported having no financial disclosures.

dbrunk@mdedge.com

When cases of COVID-19 began to surge in New York City in March 2020, Carol A. Bernstein, MD, did her best to practice psychiatry and carry out administrative tasks from a home office, but by mid-May, she became stir-crazy.

Courtesy Dr. Carol A. Bernstein

“I just couldn’t stand it, anymore,” Dr. Bernstein said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “I came back to work at least just to see my colleagues, because I felt so disconnected. Normally, in a disaster, people come together – whether it’s responding to an earthquake or a fire or whatever. People come together to provide themselves with support. They hug each other and hold each other’s hands. We could not and cannot do that in this pandemic.”

According to Dr. Bernstein, stress, fear, and uncertainty triggered by the COVID-19 pandemic require special attention to the needs of health care personnel.

“Taking care of yourself and encouraging others to do the same sustains the ability to care for those in need,” said Dr. Bernstein, who is vice chair for faculty development and well-being in the departments of psychiatry and behavioral science and obstetrics and gynecology at Montefiore Medical Center/Albert Einstein College of Medicine, New York. “This includes both meeting practical needs as well as physical and emotional self-care. Everyone is impacted by this, so emotional support needs to be available to everyone. In the psychiatric community, we have triple challenges. We have to take care of our patients, our colleagues, and ourselves. It’s a lot.”

Specific challenges for health care workers include the potential for a surge in care demand and uncertainty about future outbreaks.

“Although we don’t have [personal protective] and respirator shortages at the moment, we’re worried about the vaccine shortages,” she said. Then there’s the fact that patients with comorbid conditions have the highest risk of death and the task of providing supportive care as well as medical care. “Of course, we still have a risk of becoming infected or infecting our families. There is additional psychological stress: fear, grief, frustration, guilt, insomnia, and exhaustion.”

Now, more than a year removed from the start of the pandemic, health care personnel are experiencing compassion fatigue, which she described as the inability to feel compassion for our patients because of our inability to feel compassion for ourselves. “We’re certainly experiencing burnout, although the primary aspect of burnout that we are experiencing is emotional exhaustion,” said Dr. Bernstein, who also is a past president of the American Psychiatric Association.

General risk factors for burnout and distress include sleep deprivation, high levels of work/life conflict, work interrupted by personal concerns, high levels of anger, loneliness, or anxiety, the stress of work relationships/work outcomes, anxiety about competency, difficulty “unplugging” after work, and regular use of alcohol and other drugs. At the same time, she continued, signs of burnout and secondary traumatic stress include sadness, depression, or apathy; feeling easily frustrated; feeling isolated and disconnected from others; excessive worry or fear about something bad happening; feeling like a failure, and feeling tired, exhausted, or overwhelmed.

“Why is this crisis so hard for us docs?” she asked. “Because focusing on ourselves – with worries like ‘are we okay? Are we going to get sick?’ – compromises our focus on patients. This can lead to medical errors and unprofessional behavior. There are significant feelings of guilt that ‘I’m not doing enough.’

“This was true for a lot of us in psychiatry who were working virtually early during the pandemic while our medicine colleagues were on the front lines exposing themselves to COVID. Even the people working on the COVID units at the height on the initial surge felt guilty because treatment algorithms were changing almost every day. Fortunately, protocols are more established now, but the sense of not doing enough is pervasive and makes it difficult for us to ask for help.”

Fear of the unknown also posed a challenge to the workforce. “We didn’t know what we were dealing with at first,” she said. “The loss of control and autonomy, which is a major driver of burnout in the best of circumstances, was particularly true here in New York. People were told what to do. They were deployed into new circumstances. We experienced a significant loss of control, both of the virus and of what we were doing, and a widespread sense of isolation and loneliness.”

To cultivate resilience going forward, Dr. Bernstein advocates for the concept of psychological flexibility, which she defined as the ability to stay in contact with the present moment regardless of unpleasant thoughts, feelings, and bodily sensations, while choosing one’s behaviors based on the situation and personal values. “It is understanding that you can feel demoralized and bad one minute and better the next day,” she said. “This is a key concept for being able to continuously adapt under stressful circumstances and to tolerate uncertainty.”

She advises clinicians to identify safe areas and behaviors, and to maximize their ability to care for themselves and their families – including keeping in touch with colleagues and people you care about. “You also want to take advantage of calming skills and the maintenance of natural body rhythms,” she said. “This includes sensible nutrition and getting adequate rest and exercise.”

Dr. Bernstein also emphasized the importance of trying to maintain hope and optimism while not denying risk. “We also have to think about ethics, to provide the best possible care given the circumstances,” she said. “The crisis standards of care are necessarily different. We are not ethically required to offer futile care, but we must tell the truth.”

She pointed out that resilience is sometimes thought of as returning to the way you were before a stressful or life-altering event. “But here we refer to it as using your coping resources, connecting to others, and cultivating your values and purpose in life as you ride through this time of stress,” Dr. Bernstein said. “You are aware of the time it takes to develop and test for treatment and vaccine efficacy, and to then roll out these interventions, so you do know there will be an end to this, hopefully by the summer. While you won’t forget this time, focus on what you can control, your positive relationships, remind yourself of your purpose, and practice gratitude for what you are thankful for in your life. We need to cultivate what is positive and promote the message that emotional health should have the same priority level as physical health. The goal is to flourish.”

Dr. Bernstein reported having no financial disclosures.

dbrunk@mdedge.com

Despite slightly decreasing numbers of pregnant women hospitalized with influenza, the rate of morbidity among those who do have influenza has substantially increased from 2000 to 2015, likely due in part to an increase in comorbidities.

Maternal patients who have influenza while hospitalized for delivery are twice as likely to develop severe maternal morbidity than are those without influenza, according to findings from a new study presented at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.

Pregnant women were also at substantially greater risk of sepsis or shock, needing mechanical ventilation, and acute respiratory distress syndrome. In fact, rates of overall severe maternal morbidity and of influenza-related complications have increased in maternal patients with influenza by more than 200% from 2000 to 2015.

“It was striking to see how the rate of delivery hospitalizations complicated by influenza has remained relatively stable with a small decline, but the rates of severe maternal morbidity were increasing and so markedly among those with influenza,” Timothy Wen, MD, MPH, a maternal-fetal medicine clinical fellow at the University of California, San Francisco, said in an interview. “The findings suggest that influenza may either be a contributor to rising rates of severe maternal morbidity or synergistically amplifying existing comorbidities to worsen outcomes,” he said during his presentation.

The increased risk of influenza complications in pregnant women became particularly apparent during the 2009-2010 H1N1 influenza pandemic. “Physiologic and immunologic changes predispose pregnant patients to higher risk for complications such as pneumonia, intensive care unit admission, and inpatient mortality,” Dr. Wen told attendees. But data have been scarce since H1N1.

The researchers conducted a cross-sectional analysis of delivery hospitalizations from 2000 to 2015 using the Nationwide Inpatient Sample, which includes about 20% of all U.S. inpatient hospitalizations from all payers. They looked at all maternal patients aged 15-54 who had a diagnosis of influenza. In looking at potential associations between influenza and morbidity, they adjusted their calculations for maternal age, payer status, median income, and race/ethnicity as well as the hospital factors of location, teaching status, and region. They also adjusted for a dozen clinical factors.

Of 62.7 million hospitalizations, 0.67% involved severe maternal mortality, including the following influenza complications:

• 0.02% with shock/sepsis.
• 0.01% needing mechanical ventilation.
• 0.04% with acute respiratory distress syndrome.

The 182,228 patients with influenza represented a rate of 29 cases per 10,000 deliveries, and 2.09% of them involved severe maternal morbidity, compared to severe maternal morbidity in just 0.66% of deliveries without influenza.

When looking specifically at rates of shock/sepsis, mechanical ventilation, and acute respiratory distress syndrome, the data revealed similar trends, with substantially higher proportions of patients with influenza experiencing these complications compared to maternal patients without influenza. For example, 0.3% of patients with influenza developed shock/sepsis whereas only 0.04% of patients without influenza did. Acute respiratory distress syndrome was similarly more common in patients with flu (0.45% vs. 0.04%), as was the need for mechanical ventilation (0.09% vs. 0.01%).

During the 15-year study period, the rate of maternal hospitalizations with influenza infections declined about 1.5%, from 30 to 24 per 10,000 deliveries. But trends with severe maternal morbidity in patients with influenza went in the other direction, increasing more than 200% over 15 years, from 100 to 342 cases of severe maternal morbidity per 10,000 patients with influenza. An increase also occurred in patients without influenza, but it was more modest, a nearly 50% increase, from 53 to 79 cases per 10,000 hospitalizations.

From year to year, severe maternal morbidity increased 5.3% annually among hospitalizations with influenza – more than twice the rate of a 2.4% annual increase among hospitalizations without influenza.

The researchers found that influenza is linked to twice the risk of severe maternal morbidity (adjusted risk ratio [aRR] = 2.08, P < .01). There were similarly higher risks with influenza of sepsis/shock (aRR = 3.23), mechanical ventilation (aRR = 6.04), and acute respiratory distress syndrome (aRR = 5.76; all P < .01).

Among the possible reasons for the increase in influenza morbidity – despite a decrease in influenza infections in this population – is the increase in the medical complexity of the patient population, Dr. Wen said.

“Patients who are getting pregnant today likely have more comorbid conditions (chronic hypertension, obesity, pregestational diabetes mellitus, etc.) than they did decades prior,” Dr. Wen said. “Clinically, it means that we have a baseline patient population at a higher risk of susceptibility for influenza and its complications.”

Maternal influenza immunization rates have meanwhile stagnated, Dr. Wen added. Influenza “is something that we know is preventable, or at least mitigated, by a vaccine,” he said. “Our results serve as a reminder for clinicians to continue counseling on the importance of influenza vaccination among pregnant patients, and even in those who are planning to become pregnant.”

He said these findings suggest the need for a low threshold for treating pregnant patients who have influenza symptoms with over-the-counter therapies or closely monitoring them.

Adetola Louis-Jacques, MD, of the University of South Florida, Tampa, found the increase in morbidity in those with flu particularly unexpected and concerning.

Despite slightly decreasing numbers of pregnant women hospitalized with influenza, the rate of morbidity among those who do have influenza has substantially increased from 2000 to 2015, likely due in part to an increase in comorbidities.

Maternal patients who have influenza while hospitalized for delivery are twice as likely to develop severe maternal morbidity than are those without influenza, according to findings from a new study presented at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.

Pregnant women were also at substantially greater risk of sepsis or shock, needing mechanical ventilation, and acute respiratory distress syndrome. In fact, rates of overall severe maternal morbidity and of influenza-related complications have increased in maternal patients with influenza by more than 200% from 2000 to 2015.

“It was striking to see how the rate of delivery hospitalizations complicated by influenza has remained relatively stable with a small decline, but the rates of severe maternal morbidity were increasing and so markedly among those with influenza,” Timothy Wen, MD, MPH, a maternal-fetal medicine clinical fellow at the University of California, San Francisco, said in an interview. “The findings suggest that influenza may either be a contributor to rising rates of severe maternal morbidity or synergistically amplifying existing comorbidities to worsen outcomes,” he said during his presentation.

The increased risk of influenza complications in pregnant women became particularly apparent during the 2009-2010 H1N1 influenza pandemic. “Physiologic and immunologic changes predispose pregnant patients to higher risk for complications such as pneumonia, intensive care unit admission, and inpatient mortality,” Dr. Wen told attendees. But data have been scarce since H1N1.

The researchers conducted a cross-sectional analysis of delivery hospitalizations from 2000 to 2015 using the Nationwide Inpatient Sample, which includes about 20% of all U.S. inpatient hospitalizations from all payers. They looked at all maternal patients aged 15-54 who had a diagnosis of influenza. In looking at potential associations between influenza and morbidity, they adjusted their calculations for maternal age, payer status, median income, and race/ethnicity as well as the hospital factors of location, teaching status, and region. They also adjusted for a dozen clinical factors.

Of 62.7 million hospitalizations, 0.67% involved severe maternal mortality, including the following influenza complications:

• 0.02% with shock/sepsis.
• 0.01% needing mechanical ventilation.
• 0.04% with acute respiratory distress syndrome.

The 182,228 patients with influenza represented a rate of 29 cases per 10,000 deliveries, and 2.09% of them involved severe maternal morbidity, compared to severe maternal morbidity in just 0.66% of deliveries without influenza.

When looking specifically at rates of shock/sepsis, mechanical ventilation, and acute respiratory distress syndrome, the data revealed similar trends, with substantially higher proportions of patients with influenza experiencing these complications compared to maternal patients without influenza. For example, 0.3% of patients with influenza developed shock/sepsis whereas only 0.04% of patients without influenza did. Acute respiratory distress syndrome was similarly more common in patients with flu (0.45% vs. 0.04%), as was the need for mechanical ventilation (0.09% vs. 0.01%).

During the 15-year study period, the rate of maternal hospitalizations with influenza infections declined about 1.5%, from 30 to 24 per 10,000 deliveries. But trends with severe maternal morbidity in patients with influenza went in the other direction, increasing more than 200% over 15 years, from 100 to 342 cases of severe maternal morbidity per 10,000 patients with influenza. An increase also occurred in patients without influenza, but it was more modest, a nearly 50% increase, from 53 to 79 cases per 10,000 hospitalizations.

From year to year, severe maternal morbidity increased 5.3% annually among hospitalizations with influenza – more than twice the rate of a 2.4% annual increase among hospitalizations without influenza.

The researchers found that influenza is linked to twice the risk of severe maternal morbidity (adjusted risk ratio [aRR] = 2.08, P < .01). There were similarly higher risks with influenza of sepsis/shock (aRR = 3.23), mechanical ventilation (aRR = 6.04), and acute respiratory distress syndrome (aRR = 5.76; all P < .01).

Among the possible reasons for the increase in influenza morbidity – despite a decrease in influenza infections in this population – is the increase in the medical complexity of the patient population, Dr. Wen said.

“Patients who are getting pregnant today likely have more comorbid conditions (chronic hypertension, obesity, pregestational diabetes mellitus, etc.) than they did decades prior,” Dr. Wen said. “Clinically, it means that we have a baseline patient population at a higher risk of susceptibility for influenza and its complications.”

Maternal influenza immunization rates have meanwhile stagnated, Dr. Wen added. Influenza “is something that we know is preventable, or at least mitigated, by a vaccine,” he said. “Our results serve as a reminder for clinicians to continue counseling on the importance of influenza vaccination among pregnant patients, and even in those who are planning to become pregnant.”

He said these findings suggest the need for a low threshold for treating pregnant patients who have influenza symptoms with over-the-counter therapies or closely monitoring them.

Adetola Louis-Jacques, MD, of the University of South Florida, Tampa, found the increase in morbidity in those with flu particularly unexpected and concerning.

Despite slightly decreasing numbers of pregnant women hospitalized with influenza, the rate of morbidity among those who do have influenza has substantially increased from 2000 to 2015, likely due in part to an increase in comorbidities.

Maternal patients who have influenza while hospitalized for delivery are twice as likely to develop severe maternal morbidity than are those without influenza, according to findings from a new study presented at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.

Pregnant women were also at substantially greater risk of sepsis or shock, needing mechanical ventilation, and acute respiratory distress syndrome. In fact, rates of overall severe maternal morbidity and of influenza-related complications have increased in maternal patients with influenza by more than 200% from 2000 to 2015.

“It was striking to see how the rate of delivery hospitalizations complicated by influenza has remained relatively stable with a small decline, but the rates of severe maternal morbidity were increasing and so markedly among those with influenza,” Timothy Wen, MD, MPH, a maternal-fetal medicine clinical fellow at the University of California, San Francisco, said in an interview. “The findings suggest that influenza may either be a contributor to rising rates of severe maternal morbidity or synergistically amplifying existing comorbidities to worsen outcomes,” he said during his presentation.

The increased risk of influenza complications in pregnant women became particularly apparent during the 2009-2010 H1N1 influenza pandemic. “Physiologic and immunologic changes predispose pregnant patients to higher risk for complications such as pneumonia, intensive care unit admission, and inpatient mortality,” Dr. Wen told attendees. But data have been scarce since H1N1.

The researchers conducted a cross-sectional analysis of delivery hospitalizations from 2000 to 2015 using the Nationwide Inpatient Sample, which includes about 20% of all U.S. inpatient hospitalizations from all payers. They looked at all maternal patients aged 15-54 who had a diagnosis of influenza. In looking at potential associations between influenza and morbidity, they adjusted their calculations for maternal age, payer status, median income, and race/ethnicity as well as the hospital factors of location, teaching status, and region. They also adjusted for a dozen clinical factors.

Of 62.7 million hospitalizations, 0.67% involved severe maternal mortality, including the following influenza complications:

• 0.02% with shock/sepsis.
• 0.01% needing mechanical ventilation.
• 0.04% with acute respiratory distress syndrome.

The 182,228 patients with influenza represented a rate of 29 cases per 10,000 deliveries, and 2.09% of them involved severe maternal morbidity, compared to severe maternal morbidity in just 0.66% of deliveries without influenza.

When looking specifically at rates of shock/sepsis, mechanical ventilation, and acute respiratory distress syndrome, the data revealed similar trends, with substantially higher proportions of patients with influenza experiencing these complications compared to maternal patients without influenza. For example, 0.3% of patients with influenza developed shock/sepsis whereas only 0.04% of patients without influenza did. Acute respiratory distress syndrome was similarly more common in patients with flu (0.45% vs. 0.04%), as was the need for mechanical ventilation (0.09% vs. 0.01%).

During the 15-year study period, the rate of maternal hospitalizations with influenza infections declined about 1.5%, from 30 to 24 per 10,000 deliveries. But trends with severe maternal morbidity in patients with influenza went in the other direction, increasing more than 200% over 15 years, from 100 to 342 cases of severe maternal morbidity per 10,000 patients with influenza. An increase also occurred in patients without influenza, but it was more modest, a nearly 50% increase, from 53 to 79 cases per 10,000 hospitalizations.

From year to year, severe maternal morbidity increased 5.3% annually among hospitalizations with influenza – more than twice the rate of a 2.4% annual increase among hospitalizations without influenza.

The researchers found that influenza is linked to twice the risk of severe maternal morbidity (adjusted risk ratio [aRR] = 2.08, P < .01). There were similarly higher risks with influenza of sepsis/shock (aRR = 3.23), mechanical ventilation (aRR = 6.04), and acute respiratory distress syndrome (aRR = 5.76; all P < .01).

Among the possible reasons for the increase in influenza morbidity – despite a decrease in influenza infections in this population – is the increase in the medical complexity of the patient population, Dr. Wen said.

“Patients who are getting pregnant today likely have more comorbid conditions (chronic hypertension, obesity, pregestational diabetes mellitus, etc.) than they did decades prior,” Dr. Wen said. “Clinically, it means that we have a baseline patient population at a higher risk of susceptibility for influenza and its complications.”

Maternal influenza immunization rates have meanwhile stagnated, Dr. Wen added. Influenza “is something that we know is preventable, or at least mitigated, by a vaccine,” he said. “Our results serve as a reminder for clinicians to continue counseling on the importance of influenza vaccination among pregnant patients, and even in those who are planning to become pregnant.”

He said these findings suggest the need for a low threshold for treating pregnant patients who have influenza symptoms with over-the-counter therapies or closely monitoring them.

Adetola Louis-Jacques, MD, of the University of South Florida, Tampa, found the increase in morbidity in those with flu particularly unexpected and concerning.

Real-world experience with chimeric antigen receptor (CAR) T-cell therapies for large B-cell lymphomas compares favorably with experience in commercial and trial settings and provides new insights for predicting outcomes, according to Paolo Corradini, MD.

The 12-month duration of response (DOR) and progression-free survival (PFS) rates in 152 real-world patients treated with tisagenlecleucel (tisa-cel; Kymriah) for an approved indication were 48.4% and 26.4%, respectively, data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) and published in November 2020 in Blood Advances showed.

Those results are similar to the findings of the pivotal phase 2 JULIET trial evaluating tisa-cel in patients with DLBCL who relapsed or were refractory to at least two prior lines of therapy, Dr. Corradini said at the third European CAR T-cell Meeting, jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association.

A clinical update of the JULIET trial, as presented by Dr. Corradini and colleagues in a poster at the 2020 annual conference of the American Society of Hematology, showed a relapse-free probability of 60.4% at 24 and 30 months among 61 patients with an initial response.

The 12- and 36-month PFS rates as of February 2020, with median follow-up of 40.3 months, were 33% and 31%, respectively, and no new safety signals were identified, said Dr. Corradini, chair of hematology at the University of Milan.

Similarly, real-world data from the U.S. Lymphoma CAR T Consortium showing median PFS of 8.3 months at median follow-up of 12.9 months in 275 patients treated with axicabtagene ciloleucel (axi-cel; YESCARTA) were comparable with outcomes in the ZUMA-1 registrational trial, he noted.

An ongoing response was seen at 2 years in 39% of patients in ZUMA-1, and 3-year survival was 47%, according to an update reported at ASH 2019.

Of note, 43% of patients in the real-world study, which was published in the Journal of Clinical Oncology in September 2020, would not have met ZUMA-1 eligibility criteria because of comorbidities at the time of leukapheresis.
 

Predicting outcomes

The real-world data also demonstrated that performance status and lactate dehydrogenase (LDH) levels can predict outcomes: Patients with poor Eastern Cooperative Oncology Group performance status of 2-4 versus less than 2, and elevated LDH had shorter PFS and overall survival (OS) on both univariate and multivariate analysis, Dr. Corradini noted.

A subsequent multicenter study showed similar response rates of 70% and 68% in ZUMA-1-eligible and noneligible patients, but significantly improved DOR, PFS, and OS outcomes among the ZUMA-1-eligible patients.

The authors also looked for “clinical predictive factors or some easy clinical biomarkers to predict the outcomes in our patients receiving CAR T-cells,” and found that C-reactive protein levels of more than 30 mg at infusion were associated with poorer DOR, PFS, and OS, he said.

In 60 patients in another U.S. study of both tisa-cel- and axi-cel-treated patients at Memorial Sloan Kettering Cancer Center, 1-year event-free survival and OS were 40% and 69%, and Dr. Corradini’s experience with 55 patients at the University of Milan similarly showed 1-year PFS and OS of 40% and 70%, respectively.

“So all these studies support the notion that the results of CAR T-cells in real-world practice are durable for our patients, and are very similar to results obtained in the studies,” he said.

Other factors that have been shown to be associated with poor outcomes after CAR T-cell therapy include systemic bridging therapy, high metabolic tumor volume, and extranodal involvement; patients with these characteristics, along with those who have poor ECOG performance status or elevated LDH or CRP levels, do not comprise “a group to exclude from CAR T-cell therapy, but rather ... a group for whom there is an unmet need with our currently available treatments,” he said, adding: “So, it’s a group for which we have to do clinical trials and studies to improve the outcomes of our patient with large B-cell lymphomas.”

“These are all real-world data with commercially available products, he noted.
 

Product selection

Tisa-cel received Food and Drug Administration approval in 2017 and is used to treat relapsed or refractory acute lymphoblastic leukemia in those aged up to 25 years, and non-Hodgkin lymphoma that has relapsed or is refractory after at least two prior lines of therapy.

Axi-cel was also approved in 2017 for relapsed/refractory non-Hodgkin lymphoma, and in February 2021, after Dr. Corradini’s meeting presentation, the FDA granted a third approval to lisocabtagene maraleucel (liso-cel; Breyanzi) for this indication.

The information to date from both the trial and real-world settings are limited with respect to showing any differences in outcomes between the CAR T-cell products, but provide “an initial suggestion” that outcomes with tisa-cel and axi-cel are comparable, he said, adding that decisions should be strictly based on product registration data given the absence of reliable data for choosing one product over another.

Dr. Corradini reported honoraria and/or payment for travel and accommodations from Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, and a number of other pharmaceutical companies.

sworcester@mdedge.com

Real-world experience with chimeric antigen receptor (CAR) T-cell therapies for large B-cell lymphomas compares favorably with experience in commercial and trial settings and provides new insights for predicting outcomes, according to Paolo Corradini, MD.

The 12-month duration of response (DOR) and progression-free survival (PFS) rates in 152 real-world patients treated with tisagenlecleucel (tisa-cel; Kymriah) for an approved indication were 48.4% and 26.4%, respectively, data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) and published in November 2020 in Blood Advances showed.

Those results are similar to the findings of the pivotal phase 2 JULIET trial evaluating tisa-cel in patients with DLBCL who relapsed or were refractory to at least two prior lines of therapy, Dr. Corradini said at the third European CAR T-cell Meeting, jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association.

A clinical update of the JULIET trial, as presented by Dr. Corradini and colleagues in a poster at the 2020 annual conference of the American Society of Hematology, showed a relapse-free probability of 60.4% at 24 and 30 months among 61 patients with an initial response.

The 12- and 36-month PFS rates as of February 2020, with median follow-up of 40.3 months, were 33% and 31%, respectively, and no new safety signals were identified, said Dr. Corradini, chair of hematology at the University of Milan.

Similarly, real-world data from the U.S. Lymphoma CAR T Consortium showing median PFS of 8.3 months at median follow-up of 12.9 months in 275 patients treated with axicabtagene ciloleucel (axi-cel; YESCARTA) were comparable with outcomes in the ZUMA-1 registrational trial, he noted.

An ongoing response was seen at 2 years in 39% of patients in ZUMA-1, and 3-year survival was 47%, according to an update reported at ASH 2019.

Of note, 43% of patients in the real-world study, which was published in the Journal of Clinical Oncology in September 2020, would not have met ZUMA-1 eligibility criteria because of comorbidities at the time of leukapheresis.
 

Predicting outcomes

The real-world data also demonstrated that performance status and lactate dehydrogenase (LDH) levels can predict outcomes: Patients with poor Eastern Cooperative Oncology Group performance status of 2-4 versus less than 2, and elevated LDH had shorter PFS and overall survival (OS) on both univariate and multivariate analysis, Dr. Corradini noted.

A subsequent multicenter study showed similar response rates of 70% and 68% in ZUMA-1-eligible and noneligible patients, but significantly improved DOR, PFS, and OS outcomes among the ZUMA-1-eligible patients.

The authors also looked for “clinical predictive factors or some easy clinical biomarkers to predict the outcomes in our patients receiving CAR T-cells,” and found that C-reactive protein levels of more than 30 mg at infusion were associated with poorer DOR, PFS, and OS, he said.

In 60 patients in another U.S. study of both tisa-cel- and axi-cel-treated patients at Memorial Sloan Kettering Cancer Center, 1-year event-free survival and OS were 40% and 69%, and Dr. Corradini’s experience with 55 patients at the University of Milan similarly showed 1-year PFS and OS of 40% and 70%, respectively.

“So all these studies support the notion that the results of CAR T-cells in real-world practice are durable for our patients, and are very similar to results obtained in the studies,” he said.

Other factors that have been shown to be associated with poor outcomes after CAR T-cell therapy include systemic bridging therapy, high metabolic tumor volume, and extranodal involvement; patients with these characteristics, along with those who have poor ECOG performance status or elevated LDH or CRP levels, do not comprise “a group to exclude from CAR T-cell therapy, but rather ... a group for whom there is an unmet need with our currently available treatments,” he said, adding: “So, it’s a group for which we have to do clinical trials and studies to improve the outcomes of our patient with large B-cell lymphomas.”

“These are all real-world data with commercially available products, he noted.
 

Product selection

Tisa-cel received Food and Drug Administration approval in 2017 and is used to treat relapsed or refractory acute lymphoblastic leukemia in those aged up to 25 years, and non-Hodgkin lymphoma that has relapsed or is refractory after at least two prior lines of therapy.

Axi-cel was also approved in 2017 for relapsed/refractory non-Hodgkin lymphoma, and in February 2021, after Dr. Corradini’s meeting presentation, the FDA granted a third approval to lisocabtagene maraleucel (liso-cel; Breyanzi) for this indication.

The information to date from both the trial and real-world settings are limited with respect to showing any differences in outcomes between the CAR T-cell products, but provide “an initial suggestion” that outcomes with tisa-cel and axi-cel are comparable, he said, adding that decisions should be strictly based on product registration data given the absence of reliable data for choosing one product over another.

Dr. Corradini reported honoraria and/or payment for travel and accommodations from Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, and a number of other pharmaceutical companies.

sworcester@mdedge.com

Real-world experience with chimeric antigen receptor (CAR) T-cell therapies for large B-cell lymphomas compares favorably with experience in commercial and trial settings and provides new insights for predicting outcomes, according to Paolo Corradini, MD.

The 12-month duration of response (DOR) and progression-free survival (PFS) rates in 152 real-world patients treated with tisagenlecleucel (tisa-cel; Kymriah) for an approved indication were 48.4% and 26.4%, respectively, data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) and published in November 2020 in Blood Advances showed.

Those results are similar to the findings of the pivotal phase 2 JULIET trial evaluating tisa-cel in patients with DLBCL who relapsed or were refractory to at least two prior lines of therapy, Dr. Corradini said at the third European CAR T-cell Meeting, jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association.

A clinical update of the JULIET trial, as presented by Dr. Corradini and colleagues in a poster at the 2020 annual conference of the American Society of Hematology, showed a relapse-free probability of 60.4% at 24 and 30 months among 61 patients with an initial response.

The 12- and 36-month PFS rates as of February 2020, with median follow-up of 40.3 months, were 33% and 31%, respectively, and no new safety signals were identified, said Dr. Corradini, chair of hematology at the University of Milan.

Similarly, real-world data from the U.S. Lymphoma CAR T Consortium showing median PFS of 8.3 months at median follow-up of 12.9 months in 275 patients treated with axicabtagene ciloleucel (axi-cel; YESCARTA) were comparable with outcomes in the ZUMA-1 registrational trial, he noted.

An ongoing response was seen at 2 years in 39% of patients in ZUMA-1, and 3-year survival was 47%, according to an update reported at ASH 2019.

Of note, 43% of patients in the real-world study, which was published in the Journal of Clinical Oncology in September 2020, would not have met ZUMA-1 eligibility criteria because of comorbidities at the time of leukapheresis.
 

Predicting outcomes

The real-world data also demonstrated that performance status and lactate dehydrogenase (LDH) levels can predict outcomes: Patients with poor Eastern Cooperative Oncology Group performance status of 2-4 versus less than 2, and elevated LDH had shorter PFS and overall survival (OS) on both univariate and multivariate analysis, Dr. Corradini noted.

A subsequent multicenter study showed similar response rates of 70% and 68% in ZUMA-1-eligible and noneligible patients, but significantly improved DOR, PFS, and OS outcomes among the ZUMA-1-eligible patients.

The authors also looked for “clinical predictive factors or some easy clinical biomarkers to predict the outcomes in our patients receiving CAR T-cells,” and found that C-reactive protein levels of more than 30 mg at infusion were associated with poorer DOR, PFS, and OS, he said.

In 60 patients in another U.S. study of both tisa-cel- and axi-cel-treated patients at Memorial Sloan Kettering Cancer Center, 1-year event-free survival and OS were 40% and 69%, and Dr. Corradini’s experience with 55 patients at the University of Milan similarly showed 1-year PFS and OS of 40% and 70%, respectively.

“So all these studies support the notion that the results of CAR T-cells in real-world practice are durable for our patients, and are very similar to results obtained in the studies,” he said.

Other factors that have been shown to be associated with poor outcomes after CAR T-cell therapy include systemic bridging therapy, high metabolic tumor volume, and extranodal involvement; patients with these characteristics, along with those who have poor ECOG performance status or elevated LDH or CRP levels, do not comprise “a group to exclude from CAR T-cell therapy, but rather ... a group for whom there is an unmet need with our currently available treatments,” he said, adding: “So, it’s a group for which we have to do clinical trials and studies to improve the outcomes of our patient with large B-cell lymphomas.”

“These are all real-world data with commercially available products, he noted.
 

Product selection

Tisa-cel received Food and Drug Administration approval in 2017 and is used to treat relapsed or refractory acute lymphoblastic leukemia in those aged up to 25 years, and non-Hodgkin lymphoma that has relapsed or is refractory after at least two prior lines of therapy.

Axi-cel was also approved in 2017 for relapsed/refractory non-Hodgkin lymphoma, and in February 2021, after Dr. Corradini’s meeting presentation, the FDA granted a third approval to lisocabtagene maraleucel (liso-cel; Breyanzi) for this indication.

The information to date from both the trial and real-world settings are limited with respect to showing any differences in outcomes between the CAR T-cell products, but provide “an initial suggestion” that outcomes with tisa-cel and axi-cel are comparable, he said, adding that decisions should be strictly based on product registration data given the absence of reliable data for choosing one product over another.

Dr. Corradini reported honoraria and/or payment for travel and accommodations from Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, and a number of other pharmaceutical companies.

sworcester@mdedge.com

While the likelihood of a cesarean delivery usually drops as maternal education level increases, the disparities seen in cesarean rates between White and Black or Hispanic women actually increase with more maternal education, according to findings from a new study presented at the Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

Typically, higher maternal education is associated with a lower likelihood of cesarean delivery, but this protective effect is much smaller for Black women and nonexistent for Hispanic women, leading to bigger gaps between these groups and White women, found Yael Eliner, MD, an ob.gyn. residency applicant at Boston University who conducted this research with her colleagues in the ob.gyn. department at Lenox Hill Hospital, New York, and Hofstra University, Hempstead, N.Y..

Researchers have previously identified racial and ethnic disparities in a wide range of maternal outcomes, including mortality, overall morbidity, preterm birth, low birth weight, fetal growth restriction, hypertensive disorders of pregnancy, diabetes, and cesarean deliveries. But the researchers wanted to know if the usual protective effects seen for cesarean deliveries existed in the racial and ethnic groups with these disparities. Past studies have already found that the protective effect of maternal education is greater for White women than Black women with infant mortality and overall self-rated health.

The researchers conducted a retrospective analysis of all low-risk nulliparous, term, singleton, vertex live births to U.S. residents from 2016 to 2019 by using the natality database of the Centers for Disease Control and Prevention. They looked only at women who were non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic women. They excluded women with pregestational and gestational diabetes, chronic hypertension, and hypertensive disorders of pregnancy.

Maternal education levels were stratified into those without a high school diploma, high school graduates (including those with some college credit), college graduates, and those with advanced degrees. The total population included 2,969,207 mothers with a 23.4% cesarean delivery rate.

Before considering education or other potential confounders, the cesarean delivery rate was 27.4% in Black women and 25.6% in Asian women, compared with 22.4% in White women and 23% in Hispanic women (P < .001).

Among those with less than a high school education, Black (20.9%), Asian (23.1%), and Hispanic (17.9% cesarean delivery prevalence was greater than that among White women (17.2%) (P < .001). The same was true among those with a high school education (with or without some college): 22% of White women in this group had cesarean deliveries compared with 26.3% of Black women, 26.3% of Asian women, and 22.5% of Hispanic women (P < .001).

At higher levels of education, the disparities not only persisted but actually increased.

The prevalence of cesarean deliveries was 23% in White college graduates, compared with 32.5% of Black college graduates, 26.3% of Asian college graduates, and 27.7% of Hispanic college graduates (P < .001). Similarly, in those with an advanced degree, the prevalence of cesarean deliveries in their population set was 23.6% of Whites, 36.3% of Blacks, 26.1% of Asians, and 30.1% of Hispanics (P < .001).

After adjusting for maternal education as well as age, prepregnancy body mass index, weight gain during pregnancy, insurance type, and neonatal birth weight, the researchers still found substantial disparities in cesarean delivery rates. Black women had 1.54 times greater odds of cesarean delivery than White women (P < .001). Similarly, the odds were 1.45 times greater for Asian women and 1.24 times greater for Hispanic women (P < .001).

Controlling for race, ethnicity, and the other confounders, women with less than a high school education or a high school diploma had similar likelihoods of cesarean delivery. The likelihood of a cesarean delivery was slightly reduced for women with a college degree (odds ratio, 0.93) or advanced degree (OR, 0.88). But this protective effect did not dampen racial/ethnic disparities. In fact, even greater disparities were seen at higher levels of education.

“At each level of education, all the racial/ethnic groups had significantly higher odds of a cesarean delivery than White women,” Dr. Eliner said. “Additionally, the racial/ethnic disparity in cesarean delivery rates increased with increasing level of education, and we specifically see a meaningful jump in the odds ratio at the college graduate level.”

She pointed out that the OR for cesarean delivery in Black women was 1.4 times greater than White women in the group with less than a high school education and 1.44 times greater in those with high school diplomas. Then it jumped to 1.69 in the college graduates group and 1.7 in the advanced degree group.

Higher maternal education was associated with a lower likelihood of cesarean delivery in White women and Asian women. White women with advanced degrees were 17% less likely to have a cesarean than White women with less than a high school education, and the respective reduction in risk was 19% for Asian women.

In Black women, however, education has a much smaller protective effect: An advanced degree reduced the odds of a cesarean delivery by only 7% and no significant difference showed up between high school graduates and college graduates, Dr. Eliner reported.

In Hispanic women, no protective effect showed up, and the odds of a cesarean delivery actually increased slightly in high school and college graduates above those with less than a high school education.

Dr. Eliner discussed a couple possible reasons for a less protective effect from maternal education in Black and Hispanic groups, including higher levels of chronic stress found in past research among racial/ethnic minorities with higher levels of education.

“The impact of racism as a chronic stressor and its association with adverse obstetric and prenatal outcomes is an emerging theme in health disparity research and is yet to be fully understood,” Dr. Eliner said in an interview. “Nonetheless, there is some evidence suggesting that racial/ethnic minorities with higher levels of education suffer from higher levels of stress.”

Implicit and explicit interpersonal bias and institutional racism may also play a role in the disparities, she said, and these factors may disproportionately affect the quality of care for more educated women. She also suggested that White women may be more comfortable advocating for their care.

“While less educated women from all racial/ethnic groups may lack the self-advocacy skills to discuss their labor course, educated White women may be more confident than women from educated minority groups,” Dr. Eliner told attendees. “They may therefore be better equipped to discuss the need for a cesarean delivery with their provider.”

Dr. Eliner elaborated on this: “Given the historical and current disparities of the health care system, women in racial/ethnic minorities may potentially be guarded in their interaction with medical professionals, with a reduced trust in the health care system, and may thus not feel empowered to advocate for themselves in this setting,” she said.

Allison Bryant Mantha, MD, MPH, vice chair for quality, equity, and safety in the ob.gyn. department at Massachusetts General Hospital, Boston, suggested that bias and racism may play a role in this self-advocacy as well.

“I’m wondering if it might not be equally plausible that the advocacy might be met differently by who’s delivering the message,” Dr. Bryant Mantha said. “I think from the story of Dr. Susan Moore and patients who advocate for themselves, I think that we know there is probably some differential by who’s delivering the message.”

Finally, even though education is usually highly correlated with income and frequently used as a proxy for it, but the effect of education on income varies by race/ethnicity.

Since education alone is not sufficient to reduce these disparities, potential interventions should focus on increasing awareness of the disparities and the role of implicit bias, improving patients’ trust in the medical system, and training more doctors from underrepresented groups, Dr. Eliner said.

“I was also wondering about the overall patient choice,” said Sarahn M. Wheeler, MD, an assistant professor of ob.gyn. at Duke University Medical Center in Durham, N.C., who comoderated the session with Dr. Bryant Mantha. “Did we have any understanding of differences in patient values systems that might go into some of these differences in findings as well? There are lots of interesting concepts to explore and that this abstract brings up.”

Dr. Eliner, Dr. Wheeler, and Dr. Bryant Mantha had no disclosures.
 

While the likelihood of a cesarean delivery usually drops as maternal education level increases, the disparities seen in cesarean rates between White and Black or Hispanic women actually increase with more maternal education, according to findings from a new study presented at the Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

Typically, higher maternal education is associated with a lower likelihood of cesarean delivery, but this protective effect is much smaller for Black women and nonexistent for Hispanic women, leading to bigger gaps between these groups and White women, found Yael Eliner, MD, an ob.gyn. residency applicant at Boston University who conducted this research with her colleagues in the ob.gyn. department at Lenox Hill Hospital, New York, and Hofstra University, Hempstead, N.Y..

Researchers have previously identified racial and ethnic disparities in a wide range of maternal outcomes, including mortality, overall morbidity, preterm birth, low birth weight, fetal growth restriction, hypertensive disorders of pregnancy, diabetes, and cesarean deliveries. But the researchers wanted to know if the usual protective effects seen for cesarean deliveries existed in the racial and ethnic groups with these disparities. Past studies have already found that the protective effect of maternal education is greater for White women than Black women with infant mortality and overall self-rated health.

The researchers conducted a retrospective analysis of all low-risk nulliparous, term, singleton, vertex live births to U.S. residents from 2016 to 2019 by using the natality database of the Centers for Disease Control and Prevention. They looked only at women who were non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic women. They excluded women with pregestational and gestational diabetes, chronic hypertension, and hypertensive disorders of pregnancy.

Maternal education levels were stratified into those without a high school diploma, high school graduates (including those with some college credit), college graduates, and those with advanced degrees. The total population included 2,969,207 mothers with a 23.4% cesarean delivery rate.

Before considering education or other potential confounders, the cesarean delivery rate was 27.4% in Black women and 25.6% in Asian women, compared with 22.4% in White women and 23% in Hispanic women (P < .001).

Among those with less than a high school education, Black (20.9%), Asian (23.1%), and Hispanic (17.9% cesarean delivery prevalence was greater than that among White women (17.2%) (P < .001). The same was true among those with a high school education (with or without some college): 22% of White women in this group had cesarean deliveries compared with 26.3% of Black women, 26.3% of Asian women, and 22.5% of Hispanic women (P < .001).

At higher levels of education, the disparities not only persisted but actually increased.

The prevalence of cesarean deliveries was 23% in White college graduates, compared with 32.5% of Black college graduates, 26.3% of Asian college graduates, and 27.7% of Hispanic college graduates (P < .001). Similarly, in those with an advanced degree, the prevalence of cesarean deliveries in their population set was 23.6% of Whites, 36.3% of Blacks, 26.1% of Asians, and 30.1% of Hispanics (P < .001).

After adjusting for maternal education as well as age, prepregnancy body mass index, weight gain during pregnancy, insurance type, and neonatal birth weight, the researchers still found substantial disparities in cesarean delivery rates. Black women had 1.54 times greater odds of cesarean delivery than White women (P < .001). Similarly, the odds were 1.45 times greater for Asian women and 1.24 times greater for Hispanic women (P < .001).

Controlling for race, ethnicity, and the other confounders, women with less than a high school education or a high school diploma had similar likelihoods of cesarean delivery. The likelihood of a cesarean delivery was slightly reduced for women with a college degree (odds ratio, 0.93) or advanced degree (OR, 0.88). But this protective effect did not dampen racial/ethnic disparities. In fact, even greater disparities were seen at higher levels of education.

“At each level of education, all the racial/ethnic groups had significantly higher odds of a cesarean delivery than White women,” Dr. Eliner said. “Additionally, the racial/ethnic disparity in cesarean delivery rates increased with increasing level of education, and we specifically see a meaningful jump in the odds ratio at the college graduate level.”

She pointed out that the OR for cesarean delivery in Black women was 1.4 times greater than White women in the group with less than a high school education and 1.44 times greater in those with high school diplomas. Then it jumped to 1.69 in the college graduates group and 1.7 in the advanced degree group.

Higher maternal education was associated with a lower likelihood of cesarean delivery in White women and Asian women. White women with advanced degrees were 17% less likely to have a cesarean than White women with less than a high school education, and the respective reduction in risk was 19% for Asian women.

In Black women, however, education has a much smaller protective effect: An advanced degree reduced the odds of a cesarean delivery by only 7% and no significant difference showed up between high school graduates and college graduates, Dr. Eliner reported.

In Hispanic women, no protective effect showed up, and the odds of a cesarean delivery actually increased slightly in high school and college graduates above those with less than a high school education.

Dr. Eliner discussed a couple possible reasons for a less protective effect from maternal education in Black and Hispanic groups, including higher levels of chronic stress found in past research among racial/ethnic minorities with higher levels of education.

“The impact of racism as a chronic stressor and its association with adverse obstetric and prenatal outcomes is an emerging theme in health disparity research and is yet to be fully understood,” Dr. Eliner said in an interview. “Nonetheless, there is some evidence suggesting that racial/ethnic minorities with higher levels of education suffer from higher levels of stress.”

Implicit and explicit interpersonal bias and institutional racism may also play a role in the disparities, she said, and these factors may disproportionately affect the quality of care for more educated women. She also suggested that White women may be more comfortable advocating for their care.

“While less educated women from all racial/ethnic groups may lack the self-advocacy skills to discuss their labor course, educated White women may be more confident than women from educated minority groups,” Dr. Eliner told attendees. “They may therefore be better equipped to discuss the need for a cesarean delivery with their provider.”

Dr. Eliner elaborated on this: “Given the historical and current disparities of the health care system, women in racial/ethnic minorities may potentially be guarded in their interaction with medical professionals, with a reduced trust in the health care system, and may thus not feel empowered to advocate for themselves in this setting,” she said.

Allison Bryant Mantha, MD, MPH, vice chair for quality, equity, and safety in the ob.gyn. department at Massachusetts General Hospital, Boston, suggested that bias and racism may play a role in this self-advocacy as well.

“I’m wondering if it might not be equally plausible that the advocacy might be met differently by who’s delivering the message,” Dr. Bryant Mantha said. “I think from the story of Dr. Susan Moore and patients who advocate for themselves, I think that we know there is probably some differential by who’s delivering the message.”

Finally, even though education is usually highly correlated with income and frequently used as a proxy for it, but the effect of education on income varies by race/ethnicity.

Since education alone is not sufficient to reduce these disparities, potential interventions should focus on increasing awareness of the disparities and the role of implicit bias, improving patients’ trust in the medical system, and training more doctors from underrepresented groups, Dr. Eliner said.

“I was also wondering about the overall patient choice,” said Sarahn M. Wheeler, MD, an assistant professor of ob.gyn. at Duke University Medical Center in Durham, N.C., who comoderated the session with Dr. Bryant Mantha. “Did we have any understanding of differences in patient values systems that might go into some of these differences in findings as well? There are lots of interesting concepts to explore and that this abstract brings up.”

Dr. Eliner, Dr. Wheeler, and Dr. Bryant Mantha had no disclosures.
 

While the likelihood of a cesarean delivery usually drops as maternal education level increases, the disparities seen in cesarean rates between White and Black or Hispanic women actually increase with more maternal education, according to findings from a new study presented at the Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine.

Typically, higher maternal education is associated with a lower likelihood of cesarean delivery, but this protective effect is much smaller for Black women and nonexistent for Hispanic women, leading to bigger gaps between these groups and White women, found Yael Eliner, MD, an ob.gyn. residency applicant at Boston University who conducted this research with her colleagues in the ob.gyn. department at Lenox Hill Hospital, New York, and Hofstra University, Hempstead, N.Y..

Researchers have previously identified racial and ethnic disparities in a wide range of maternal outcomes, including mortality, overall morbidity, preterm birth, low birth weight, fetal growth restriction, hypertensive disorders of pregnancy, diabetes, and cesarean deliveries. But the researchers wanted to know if the usual protective effects seen for cesarean deliveries existed in the racial and ethnic groups with these disparities. Past studies have already found that the protective effect of maternal education is greater for White women than Black women with infant mortality and overall self-rated health.

The researchers conducted a retrospective analysis of all low-risk nulliparous, term, singleton, vertex live births to U.S. residents from 2016 to 2019 by using the natality database of the Centers for Disease Control and Prevention. They looked only at women who were non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic women. They excluded women with pregestational and gestational diabetes, chronic hypertension, and hypertensive disorders of pregnancy.

Maternal education levels were stratified into those without a high school diploma, high school graduates (including those with some college credit), college graduates, and those with advanced degrees. The total population included 2,969,207 mothers with a 23.4% cesarean delivery rate.

Before considering education or other potential confounders, the cesarean delivery rate was 27.4% in Black women and 25.6% in Asian women, compared with 22.4% in White women and 23% in Hispanic women (P < .001).

Among those with less than a high school education, Black (20.9%), Asian (23.1%), and Hispanic (17.9% cesarean delivery prevalence was greater than that among White women (17.2%) (P < .001). The same was true among those with a high school education (with or without some college): 22% of White women in this group had cesarean deliveries compared with 26.3% of Black women, 26.3% of Asian women, and 22.5% of Hispanic women (P < .001).

At higher levels of education, the disparities not only persisted but actually increased.

The prevalence of cesarean deliveries was 23% in White college graduates, compared with 32.5% of Black college graduates, 26.3% of Asian college graduates, and 27.7% of Hispanic college graduates (P < .001). Similarly, in those with an advanced degree, the prevalence of cesarean deliveries in their population set was 23.6% of Whites, 36.3% of Blacks, 26.1% of Asians, and 30.1% of Hispanics (P < .001).

After adjusting for maternal education as well as age, prepregnancy body mass index, weight gain during pregnancy, insurance type, and neonatal birth weight, the researchers still found substantial disparities in cesarean delivery rates. Black women had 1.54 times greater odds of cesarean delivery than White women (P < .001). Similarly, the odds were 1.45 times greater for Asian women and 1.24 times greater for Hispanic women (P < .001).

Controlling for race, ethnicity, and the other confounders, women with less than a high school education or a high school diploma had similar likelihoods of cesarean delivery. The likelihood of a cesarean delivery was slightly reduced for women with a college degree (odds ratio, 0.93) or advanced degree (OR, 0.88). But this protective effect did not dampen racial/ethnic disparities. In fact, even greater disparities were seen at higher levels of education.

“At each level of education, all the racial/ethnic groups had significantly higher odds of a cesarean delivery than White women,” Dr. Eliner said. “Additionally, the racial/ethnic disparity in cesarean delivery rates increased with increasing level of education, and we specifically see a meaningful jump in the odds ratio at the college graduate level.”

She pointed out that the OR for cesarean delivery in Black women was 1.4 times greater than White women in the group with less than a high school education and 1.44 times greater in those with high school diplomas. Then it jumped to 1.69 in the college graduates group and 1.7 in the advanced degree group.

Higher maternal education was associated with a lower likelihood of cesarean delivery in White women and Asian women. White women with advanced degrees were 17% less likely to have a cesarean than White women with less than a high school education, and the respective reduction in risk was 19% for Asian women.

In Black women, however, education has a much smaller protective effect: An advanced degree reduced the odds of a cesarean delivery by only 7% and no significant difference showed up between high school graduates and college graduates, Dr. Eliner reported.

In Hispanic women, no protective effect showed up, and the odds of a cesarean delivery actually increased slightly in high school and college graduates above those with less than a high school education.

Dr. Eliner discussed a couple possible reasons for a less protective effect from maternal education in Black and Hispanic groups, including higher levels of chronic stress found in past research among racial/ethnic minorities with higher levels of education.

“The impact of racism as a chronic stressor and its association with adverse obstetric and prenatal outcomes is an emerging theme in health disparity research and is yet to be fully understood,” Dr. Eliner said in an interview. “Nonetheless, there is some evidence suggesting that racial/ethnic minorities with higher levels of education suffer from higher levels of stress.”

Implicit and explicit interpersonal bias and institutional racism may also play a role in the disparities, she said, and these factors may disproportionately affect the quality of care for more educated women. She also suggested that White women may be more comfortable advocating for their care.

“While less educated women from all racial/ethnic groups may lack the self-advocacy skills to discuss their labor course, educated White women may be more confident than women from educated minority groups,” Dr. Eliner told attendees. “They may therefore be better equipped to discuss the need for a cesarean delivery with their provider.”

Dr. Eliner elaborated on this: “Given the historical and current disparities of the health care system, women in racial/ethnic minorities may potentially be guarded in their interaction with medical professionals, with a reduced trust in the health care system, and may thus not feel empowered to advocate for themselves in this setting,” she said.

Allison Bryant Mantha, MD, MPH, vice chair for quality, equity, and safety in the ob.gyn. department at Massachusetts General Hospital, Boston, suggested that bias and racism may play a role in this self-advocacy as well.

“I’m wondering if it might not be equally plausible that the advocacy might be met differently by who’s delivering the message,” Dr. Bryant Mantha said. “I think from the story of Dr. Susan Moore and patients who advocate for themselves, I think that we know there is probably some differential by who’s delivering the message.”

Finally, even though education is usually highly correlated with income and frequently used as a proxy for it, but the effect of education on income varies by race/ethnicity.

Since education alone is not sufficient to reduce these disparities, potential interventions should focus on increasing awareness of the disparities and the role of implicit bias, improving patients’ trust in the medical system, and training more doctors from underrepresented groups, Dr. Eliner said.

“I was also wondering about the overall patient choice,” said Sarahn M. Wheeler, MD, an assistant professor of ob.gyn. at Duke University Medical Center in Durham, N.C., who comoderated the session with Dr. Bryant Mantha. “Did we have any understanding of differences in patient values systems that might go into some of these differences in findings as well? There are lots of interesting concepts to explore and that this abstract brings up.”

Dr. Eliner, Dr. Wheeler, and Dr. Bryant Mantha had no disclosures.
 

Research has shown that, compared with their urban counterparts, rural cancer patients have higher cancer-related mortality and other negative treatment outcomes.

Among other explanations, the disparity has been attributed to lower education and income levels, medical and behavioral risk factors, differences in health literacy, and lower confidence in the medical system among rural residents (JCO Oncol Pract. 2020 Jul;16(7):422-30).

The COVID-19 and Oncology Patient Experience Consortium

Ms. Daniels explained that the COVID-19 and Oncology Patient Experience (COPES) Consortium was created to investigate various aspects of the patient experience during the pandemic. Three cancer centers – Moffitt Cancer Center, Huntsman Cancer Institute, and the Sylvester Comprehensive Cancer Center – participate in COPES.

At Huntsman, investigators studied social and health behaviors of cancer patients to assess whether there was a difference between those from rural and urban areas. The researchers looked at the impact of the pandemic on psychosocial outcomes, preventive measures patients implemented, and their perceptions of the risk of SARS-CoV-2 infection.

The team’s hypothesis was that rural patients might be more vulnerable than urban patients to the effects of social isolation, emotional distress, and health-adverse behaviors, but the investigators noted that there has been no prior research on the topic.
 

Assessing behaviors, attitudes, and outcomes

Between August and September 2020, the researchers surveyed 1,328 adult cancer patients who had visited Huntsman in the previous 4 years and who were enrolled in Huntsman’s Total Cancer Care or Precision Exercise Prescription studies.

Patients completed questionnaires that encompassed demographic and clinical factors, employment status, health behaviors, and infection preventive measures. Questionnaires were provided in electronic, paper, or phone-based formats. Information regarding age, race, ethnicity, and tumor stage was abstracted from Huntsman’s electronic health record.

Modifications in daily life and social interaction were assessed on a 5-point scale. Changes in exercise habits and alcohol consumption were assessed on a 3-point scale. Infection mitigation measures (the use of face masks and hand sanitizer) and perceptions about the likelihood of SARS-CoV-2 infection were measured.

The rural-urban community area codes system, which classifies U.S. census tracts by measures of population density, urbanization, and daily commuting, was utilized to categorize patients into rural and urban residences.
 

Characteristics of urban and rural cancer patients

There were 997 urban and 331 rural participants. The mean age was 60.1 years in the urban population and 62.6 years in the rural population (P = .01). There were no urban-rural differences in sex, ethnicity, cancer stage, or body mass index.

More urban than rural participants were employed full- or part-time (45% vs. 37%; P = .045). The rural counties had more patients who were not currently employed, primarily due to retirement (77% vs. 69% urban; P < .001).

“No health insurance coverage” was reported by 2% of urban and 4% of rural participants (P = .009), and 85% of all patients reported “good” to “excellent” overall health. Cancer patients in rural counties were significantly more likely to have ever smoked (37% vs. 25% urban; P = .001). In addition, alcohol consumption in the previous year was higher in rural patients. “Every day to less than once monthly” alcohol usage was reported by 44% of urban and 60% of rural patients (P < .001).
 

Changes in daily life and health-related behavior during the pandemic

Urban patients were more likely to report changes in their daily lives due to the pandemic. Specifically, 35% of urban patients and 26% of rural patients said the pandemic had changed their daily life “a lot” (P = .001).

However, there were no major differences between urban and rural patients when it came to changes in social interaction in the past month or feeling lonely in the past month (P = .45 and P = .88, respectively). Similarly, there were no significant differences for changes in alcohol consumption between the groups (P = .90).

Changes in exercise habits due to the pandemic were more common among patients in urban counties (51% vs. 39% rural; P < .001), though similar percentages of patients reported exercising less (44% urban vs. 45% rural) or more frequently (24% urban vs. 20% rural).

In terms of infection mitigation measures, urban patients were more likely to use face masks “very often” (83% vs. 66% rural; P < .001), while hand sanitizer was used “very often” among 66% of urban and 57% of rural participants (P = .05).

Urban participants were more likely than were their rural counterparts to think themselves “somewhat” or “very” likely to develop COVID-19 (22% vs. 14%; P = .04).

It might be short-sighted for oncology and public health specialists to be dismissive of differences in infection mitigation behaviors and perceptions of vulnerability to SARS-CoV-2 infection. Those behaviors and perceptions of risk could lead to lower vaccination rates in rural areas. If that occurs, there would be major negative consequences for the long-term health of rural communities and their medically vulnerable residents.
 

Future directions

Although the first 6 months of the COVID-19 pandemic had disparate effects on cancer patients living in rural and urban counties, the reasons for the disparities are complex and not easily explained by this study.

It is possible that sequential administration of the survey during the pandemic would have uncovered greater variances in attitude and health-related behaviors.

As Ms. Daniels noted, when the survey was performed, Utah had not experienced a high frequency of COVID-19 cases. Furthermore, different levels of restrictions were implemented on a county-by-county basis, potentially influencing patients’ behaviors, psychosocial adjustment, and perceptions of risk.

In addition, there may have been differences in unmeasured endpoints (infection rates, medical care utilization via telemedicine, hospitalization rates, late effects, and mortality) between the urban and rural populations.

As the investigators concluded, further research is needed to better characterize the pandemic’s short- and long-term effects on cancer patients in rural and urban settings and appropriate interventions. Such studies may yield insights into the various facets of the well-documented “rural health gap” in cancer outcomes and interventions that could narrow the gap in spheres beyond the COVID-19 pandemic.

Ms. Daniels reported having no relevant disclosures.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Research has shown that, compared with their urban counterparts, rural cancer patients have higher cancer-related mortality and other negative treatment outcomes.

Among other explanations, the disparity has been attributed to lower education and income levels, medical and behavioral risk factors, differences in health literacy, and lower confidence in the medical system among rural residents (JCO Oncol Pract. 2020 Jul;16(7):422-30).

The COVID-19 and Oncology Patient Experience Consortium

Ms. Daniels explained that the COVID-19 and Oncology Patient Experience (COPES) Consortium was created to investigate various aspects of the patient experience during the pandemic. Three cancer centers – Moffitt Cancer Center, Huntsman Cancer Institute, and the Sylvester Comprehensive Cancer Center – participate in COPES.

At Huntsman, investigators studied social and health behaviors of cancer patients to assess whether there was a difference between those from rural and urban areas. The researchers looked at the impact of the pandemic on psychosocial outcomes, preventive measures patients implemented, and their perceptions of the risk of SARS-CoV-2 infection.

The team’s hypothesis was that rural patients might be more vulnerable than urban patients to the effects of social isolation, emotional distress, and health-adverse behaviors, but the investigators noted that there has been no prior research on the topic.
 

Assessing behaviors, attitudes, and outcomes

Between August and September 2020, the researchers surveyed 1,328 adult cancer patients who had visited Huntsman in the previous 4 years and who were enrolled in Huntsman’s Total Cancer Care or Precision Exercise Prescription studies.

Patients completed questionnaires that encompassed demographic and clinical factors, employment status, health behaviors, and infection preventive measures. Questionnaires were provided in electronic, paper, or phone-based formats. Information regarding age, race, ethnicity, and tumor stage was abstracted from Huntsman’s electronic health record.

Modifications in daily life and social interaction were assessed on a 5-point scale. Changes in exercise habits and alcohol consumption were assessed on a 3-point scale. Infection mitigation measures (the use of face masks and hand sanitizer) and perceptions about the likelihood of SARS-CoV-2 infection were measured.

The rural-urban community area codes system, which classifies U.S. census tracts by measures of population density, urbanization, and daily commuting, was utilized to categorize patients into rural and urban residences.
 

Characteristics of urban and rural cancer patients

There were 997 urban and 331 rural participants. The mean age was 60.1 years in the urban population and 62.6 years in the rural population (P = .01). There were no urban-rural differences in sex, ethnicity, cancer stage, or body mass index.

More urban than rural participants were employed full- or part-time (45% vs. 37%; P = .045). The rural counties had more patients who were not currently employed, primarily due to retirement (77% vs. 69% urban; P < .001).

“No health insurance coverage” was reported by 2% of urban and 4% of rural participants (P = .009), and 85% of all patients reported “good” to “excellent” overall health. Cancer patients in rural counties were significantly more likely to have ever smoked (37% vs. 25% urban; P = .001). In addition, alcohol consumption in the previous year was higher in rural patients. “Every day to less than once monthly” alcohol usage was reported by 44% of urban and 60% of rural patients (P < .001).
 

Changes in daily life and health-related behavior during the pandemic

Urban patients were more likely to report changes in their daily lives due to the pandemic. Specifically, 35% of urban patients and 26% of rural patients said the pandemic had changed their daily life “a lot” (P = .001).

However, there were no major differences between urban and rural patients when it came to changes in social interaction in the past month or feeling lonely in the past month (P = .45 and P = .88, respectively). Similarly, there were no significant differences for changes in alcohol consumption between the groups (P = .90).

Changes in exercise habits due to the pandemic were more common among patients in urban counties (51% vs. 39% rural; P < .001), though similar percentages of patients reported exercising less (44% urban vs. 45% rural) or more frequently (24% urban vs. 20% rural).

In terms of infection mitigation measures, urban patients were more likely to use face masks “very often” (83% vs. 66% rural; P < .001), while hand sanitizer was used “very often” among 66% of urban and 57% of rural participants (P = .05).

Urban participants were more likely than were their rural counterparts to think themselves “somewhat” or “very” likely to develop COVID-19 (22% vs. 14%; P = .04).

It might be short-sighted for oncology and public health specialists to be dismissive of differences in infection mitigation behaviors and perceptions of vulnerability to SARS-CoV-2 infection. Those behaviors and perceptions of risk could lead to lower vaccination rates in rural areas. If that occurs, there would be major negative consequences for the long-term health of rural communities and their medically vulnerable residents.
 

Future directions

Although the first 6 months of the COVID-19 pandemic had disparate effects on cancer patients living in rural and urban counties, the reasons for the disparities are complex and not easily explained by this study.

It is possible that sequential administration of the survey during the pandemic would have uncovered greater variances in attitude and health-related behaviors.

As Ms. Daniels noted, when the survey was performed, Utah had not experienced a high frequency of COVID-19 cases. Furthermore, different levels of restrictions were implemented on a county-by-county basis, potentially influencing patients’ behaviors, psychosocial adjustment, and perceptions of risk.

In addition, there may have been differences in unmeasured endpoints (infection rates, medical care utilization via telemedicine, hospitalization rates, late effects, and mortality) between the urban and rural populations.

As the investigators concluded, further research is needed to better characterize the pandemic’s short- and long-term effects on cancer patients in rural and urban settings and appropriate interventions. Such studies may yield insights into the various facets of the well-documented “rural health gap” in cancer outcomes and interventions that could narrow the gap in spheres beyond the COVID-19 pandemic.

Ms. Daniels reported having no relevant disclosures.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Research has shown that, compared with their urban counterparts, rural cancer patients have higher cancer-related mortality and other negative treatment outcomes.

Among other explanations, the disparity has been attributed to lower education and income levels, medical and behavioral risk factors, differences in health literacy, and lower confidence in the medical system among rural residents (JCO Oncol Pract. 2020 Jul;16(7):422-30).

The COVID-19 and Oncology Patient Experience Consortium

Ms. Daniels explained that the COVID-19 and Oncology Patient Experience (COPES) Consortium was created to investigate various aspects of the patient experience during the pandemic. Three cancer centers – Moffitt Cancer Center, Huntsman Cancer Institute, and the Sylvester Comprehensive Cancer Center – participate in COPES.

At Huntsman, investigators studied social and health behaviors of cancer patients to assess whether there was a difference between those from rural and urban areas. The researchers looked at the impact of the pandemic on psychosocial outcomes, preventive measures patients implemented, and their perceptions of the risk of SARS-CoV-2 infection.

The team’s hypothesis was that rural patients might be more vulnerable than urban patients to the effects of social isolation, emotional distress, and health-adverse behaviors, but the investigators noted that there has been no prior research on the topic.
 

Assessing behaviors, attitudes, and outcomes

Between August and September 2020, the researchers surveyed 1,328 adult cancer patients who had visited Huntsman in the previous 4 years and who were enrolled in Huntsman’s Total Cancer Care or Precision Exercise Prescription studies.

Patients completed questionnaires that encompassed demographic and clinical factors, employment status, health behaviors, and infection preventive measures. Questionnaires were provided in electronic, paper, or phone-based formats. Information regarding age, race, ethnicity, and tumor stage was abstracted from Huntsman’s electronic health record.

Modifications in daily life and social interaction were assessed on a 5-point scale. Changes in exercise habits and alcohol consumption were assessed on a 3-point scale. Infection mitigation measures (the use of face masks and hand sanitizer) and perceptions about the likelihood of SARS-CoV-2 infection were measured.

The rural-urban community area codes system, which classifies U.S. census tracts by measures of population density, urbanization, and daily commuting, was utilized to categorize patients into rural and urban residences.
 

Characteristics of urban and rural cancer patients

There were 997 urban and 331 rural participants. The mean age was 60.1 years in the urban population and 62.6 years in the rural population (P = .01). There were no urban-rural differences in sex, ethnicity, cancer stage, or body mass index.

More urban than rural participants were employed full- or part-time (45% vs. 37%; P = .045). The rural counties had more patients who were not currently employed, primarily due to retirement (77% vs. 69% urban; P < .001).

“No health insurance coverage” was reported by 2% of urban and 4% of rural participants (P = .009), and 85% of all patients reported “good” to “excellent” overall health. Cancer patients in rural counties were significantly more likely to have ever smoked (37% vs. 25% urban; P = .001). In addition, alcohol consumption in the previous year was higher in rural patients. “Every day to less than once monthly” alcohol usage was reported by 44% of urban and 60% of rural patients (P < .001).
 

Changes in daily life and health-related behavior during the pandemic

Urban patients were more likely to report changes in their daily lives due to the pandemic. Specifically, 35% of urban patients and 26% of rural patients said the pandemic had changed their daily life “a lot” (P = .001).

However, there were no major differences between urban and rural patients when it came to changes in social interaction in the past month or feeling lonely in the past month (P = .45 and P = .88, respectively). Similarly, there were no significant differences for changes in alcohol consumption between the groups (P = .90).

Changes in exercise habits due to the pandemic were more common among patients in urban counties (51% vs. 39% rural; P < .001), though similar percentages of patients reported exercising less (44% urban vs. 45% rural) or more frequently (24% urban vs. 20% rural).

In terms of infection mitigation measures, urban patients were more likely to use face masks “very often” (83% vs. 66% rural; P < .001), while hand sanitizer was used “very often” among 66% of urban and 57% of rural participants (P = .05).

Urban participants were more likely than were their rural counterparts to think themselves “somewhat” or “very” likely to develop COVID-19 (22% vs. 14%; P = .04).

It might be short-sighted for oncology and public health specialists to be dismissive of differences in infection mitigation behaviors and perceptions of vulnerability to SARS-CoV-2 infection. Those behaviors and perceptions of risk could lead to lower vaccination rates in rural areas. If that occurs, there would be major negative consequences for the long-term health of rural communities and their medically vulnerable residents.
 

Future directions

Although the first 6 months of the COVID-19 pandemic had disparate effects on cancer patients living in rural and urban counties, the reasons for the disparities are complex and not easily explained by this study.

It is possible that sequential administration of the survey during the pandemic would have uncovered greater variances in attitude and health-related behaviors.

As Ms. Daniels noted, when the survey was performed, Utah had not experienced a high frequency of COVID-19 cases. Furthermore, different levels of restrictions were implemented on a county-by-county basis, potentially influencing patients’ behaviors, psychosocial adjustment, and perceptions of risk.

In addition, there may have been differences in unmeasured endpoints (infection rates, medical care utilization via telemedicine, hospitalization rates, late effects, and mortality) between the urban and rural populations.

As the investigators concluded, further research is needed to better characterize the pandemic’s short- and long-term effects on cancer patients in rural and urban settings and appropriate interventions. Such studies may yield insights into the various facets of the well-documented “rural health gap” in cancer outcomes and interventions that could narrow the gap in spheres beyond the COVID-19 pandemic.

Ms. Daniels reported having no relevant disclosures.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Despite improvements in prevention of graft-versus-host disease, chronic GVHD still occurs in 10%-50% of patients who undergo an allogeneic hematopoietic stem cell transplant, and these patients may require prolonged treatment with multiple lines of therapy, said a hematologist and transplant researcher.

“More effective, less toxic therapies for chronic GVHD are needed,” Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Research Center in Seattle said at the Transplant & Cellular Therapies Meetings.

Dr. Lee reviewed clinical trials for chronic GVHD at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Although the incidence of chronic GVHD has gradually declined over the last 40 years and both relapse-free and overall survival following a chronic GVHD diagnosis have improved, “for patients who are diagnosed with chronic GVHD, they still will see many lines of therapy and many years of therapy,” she said.

Among 148 patients with chronic GVHD treated at her center, for example, 66% went on to two lines of therapy, 50% went on to three lines, 37% required four lines of therapy, and 20% needed five lines or more.

Salvage therapies for patients with chronic GVHD have evolved away from immunomodulators and immunosuppressants in the early 1990s, toward monoclonal antibodies such as rituximab in the early 2000s, to interleukin-2 and to tyrosine kinase inhibitors such as ruxolitinib (Jakafi) and ibrutinib (Imbruvica).

There are currently 36 agents that are FDA approved for at least one indication and can also be prescribed for the treatment of chronic GVHD, Dr. Lee noted.
 

Treatment goals

Dr. Lee laid out six goals for treating patients with chronic GVHD. They include:

• Controlling current signs and symptoms, measured by response rates and patient-reported outcomes
• Preventing further tissue and organ damage
• Minimizing toxicity
• Maintaining graft-versus-tumor effect
• Achieving graft tolerance and stopping immunosuppression
• Decreasing nonrelapse mortality and improving survival

Active trials

Dr. Lee identified 33 trials with chronic GVHD as an indication that are currently recruiting, and an additional 13 trials that are active but closed to recruiting. The trials can be generally grouped by mechanism of action, and involve agents targeting T-regulatory cells, B cells and/or B-cell receptor (BCR) signaling, monocytes/macrophages, costimulatory blockage, a proteasome inhibition, Janus kinase (JAK) 1/2 inhibitors, ROCK2 inhibitors, hedgehog pathway inhibition, cellular therapy, and organ-targeted therapy.

Most of the trials have overall response rate as the primary endpoint, and all but five are currently in phase 1 or 2. The currently active phase 3 trials include two with ibrutinib, one with the investigational agent itacitinib, one with ruxolitinib, and one with mesenchymal stem cells.

“I’ll note that, when results are reported, the denominator really matters for the overall response rate, especially if you’re talking about small trials, because if you require the patient to be treated with an agent for a certain period of time, and you take out all the people who didn’t make it to that time point, then your overall response rate looks better,” she said.
 

BTK inhibitors

The first-in-class Bruton tyrosine kinase (BTK) inhibitor ibrutinib was the first and thus far only agent approved by the Food and Drug Administration for chronic GVHD. The approval was based on a single-arm, multicenter trial with 42 patients.

The ORR in this trial was 69%, consisting of 31% complete responses and 38% partial responses, with a duration of response longer than 10 months in slightly more than half of all patients. In all, 24% of patients had improvement of symptoms in two consecutive visits, and 29% continued on ibrutinib at the time of the primary analysis in 2017.

Based on these promising results, acalabrutinib, which is more potent and selective for BTK than ibrutinib, with no effect on either platelets or natural killer cells, is currently under investigation in a phase 2 trial in 50 patients at a dose of 100 mg orally twice daily.
 

JAK1/2 inhibition

The JAK1 inhibitor itacitinib failed to meet its primary ORR endpoint in the phase 3 GRAVITAS-301 study, according to a press release, but the manufacturer (Incyte) said that it is continuing its commitment to JAK inhibitors with ruxolitinib, which has shown activity against acute, steroid-refractory GVHD, and is being explored for prevention of chronic GVHD in the randomized, phase 3 REACH3 study.

The trial met its primary endpoint for a higher ORR at week 24 with ruxolitinib versus best available therapy, at 49.7% versus 25.6%, respectively, which translated into an odds ratio for response with the JAK inhibitor of 2.99 (P < .0001).
 

Selective T-cell expansion

Efavaleukin alfa is an IL-2-mutated protein (mutein), with a mutation in the IL-2RB-binding portion of IL-2 causing increased selectivity for regulatory T-cell expansion. It is bound to an IgG-Fc domain that is itself mutated, with reduced Fc receptor binding and IgG effector function to give it a longer half life. This agent is being studied in a phase 1/2 trial in a subcutaneous formulation delivered every 1 or 2 weeks to 68 patients.

Monocyte/macrophage depletion

Axatilimab is a high-affinity antibody targeting colony stimulating factor–1 receptor (CSF-1R) expressed on monocytes and macrophages. By blocking CSF-1R, it depletes circulation of nonclassical monocytes and prevents the differentiation and survival of M2 macrophages in tissue.

It is currently being investigated 30 patients in a phase 1/2 study in an intravenous formulation delivered over 30 minutes every 2-4 weeks.
 

Hedgehog pathway inhibition

There is evidence suggesting that hedgehog pathway inhibition can lessen fibrosis. Glasdegib (Daurismo) a potent selective oral inhibitor of the hedgehog signaling pathway, is approved for use with low-dose cytarabine for patients with newly diagnosed acute myeloid leukemia aged older than 75 years or have comorbidities precluding intensive chemotherapy.

This agent is associated with drug intolerance because of muscle spasms, dysgeusia, and alopecia, however.

The drug is currently in phase 1/2 at a dose of 50 mg orally per day in 20 patients.
 

ROCK2 inhibition

Belumosudil (formerly KD025) “appears to rebalance the immune system,” Dr. Lee said. Investigators think that the drug dampens an autoaggressive inflammatory response by selective inhibition of ROCK2.

This drug has been studied in a dose-escalation study and a phase 2 trial, in which 132 participants were randomized to receive belumosudil 200 mg either once or twice daily.

At a median follow-up of 8 months, the ORR with belumosudil 200 mg once and twice daily was 73% and 74%, respectively. Similar results were seen in patients who had previously received either ruxolitinib or ibrutinib. High response rates were seen in patients with severe chronic GVHD, involvement of four or more organs and a refractory response to their last line of therapy.
 

Hard-to-manage patients

“We’re very hopeful for many of these agents, but we have to acknowledge that there are still many management dilemmas, patients that we just don’t really know what to do with,” Dr. Lee said. “These include patients who have bad sclerosis and fasciitis, nonhealing skin ulcers, bronchiolitis obliterans, serositis that can be very difficult to manage, severe keratoconjunctivitis that can be eyesight threatening, nonhealing mouth ulcers, esophageal structures, and always patients who have frequent infections.

“We are hopeful that some these agents will be useful for our patients who have severe manifestations, but often the number of patients with these manifestations in the trials is too low to say something specific about them,” she added.
 

‘Exciting time’

“It’s an exciting time because there are a lot of different drugs that are being studied for chronic GVHD,” commented Betty Hamilton, MD, a hematologist/oncologist at the Cleveland Clinic.

“I think that where the field is going in terms of treatment is recognizing that chronic GVHD is a pretty heterogeneous disease, and we have to learn even more about the underlying biologic pathways to be able to determine which class of drugs to use and when,” she said in an interview.

She agreed with Dr. Lee that the goals of treating patients with chronic GVHD include improving symptoms and quality, preventing progression, ideally tapering patients off immunosuppression, and achieving a balance between preventing negative consequences of GVHD while maintain the benefits of a graft-versus-leukemia effect.

“In our center, drug choice is based on physician preference and comfort with how often they’ve used the drug, patients’ comorbidities, toxicities of the drug, and logistical considerations,” Dr. Hamilton said.

Dr. Lee disclosed consulting activities for Pfizer and Kadmon, travel and lodging from Amgen, and research funding from those companies and others. Dr. Hamilton disclosed consulting for Syndax and Incyte.

Despite improvements in prevention of graft-versus-host disease, chronic GVHD still occurs in 10%-50% of patients who undergo an allogeneic hematopoietic stem cell transplant, and these patients may require prolonged treatment with multiple lines of therapy, said a hematologist and transplant researcher.

“More effective, less toxic therapies for chronic GVHD are needed,” Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Research Center in Seattle said at the Transplant & Cellular Therapies Meetings.

Dr. Lee reviewed clinical trials for chronic GVHD at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Although the incidence of chronic GVHD has gradually declined over the last 40 years and both relapse-free and overall survival following a chronic GVHD diagnosis have improved, “for patients who are diagnosed with chronic GVHD, they still will see many lines of therapy and many years of therapy,” she said.

Among 148 patients with chronic GVHD treated at her center, for example, 66% went on to two lines of therapy, 50% went on to three lines, 37% required four lines of therapy, and 20% needed five lines or more.

Salvage therapies for patients with chronic GVHD have evolved away from immunomodulators and immunosuppressants in the early 1990s, toward monoclonal antibodies such as rituximab in the early 2000s, to interleukin-2 and to tyrosine kinase inhibitors such as ruxolitinib (Jakafi) and ibrutinib (Imbruvica).

There are currently 36 agents that are FDA approved for at least one indication and can also be prescribed for the treatment of chronic GVHD, Dr. Lee noted.
 

Treatment goals

Dr. Lee laid out six goals for treating patients with chronic GVHD. They include:

• Controlling current signs and symptoms, measured by response rates and patient-reported outcomes
• Preventing further tissue and organ damage
• Minimizing toxicity
• Maintaining graft-versus-tumor effect
• Achieving graft tolerance and stopping immunosuppression
• Decreasing nonrelapse mortality and improving survival

Active trials

Dr. Lee identified 33 trials with chronic GVHD as an indication that are currently recruiting, and an additional 13 trials that are active but closed to recruiting. The trials can be generally grouped by mechanism of action, and involve agents targeting T-regulatory cells, B cells and/or B-cell receptor (BCR) signaling, monocytes/macrophages, costimulatory blockage, a proteasome inhibition, Janus kinase (JAK) 1/2 inhibitors, ROCK2 inhibitors, hedgehog pathway inhibition, cellular therapy, and organ-targeted therapy.

Most of the trials have overall response rate as the primary endpoint, and all but five are currently in phase 1 or 2. The currently active phase 3 trials include two with ibrutinib, one with the investigational agent itacitinib, one with ruxolitinib, and one with mesenchymal stem cells.

“I’ll note that, when results are reported, the denominator really matters for the overall response rate, especially if you’re talking about small trials, because if you require the patient to be treated with an agent for a certain period of time, and you take out all the people who didn’t make it to that time point, then your overall response rate looks better,” she said.
 

BTK inhibitors

The first-in-class Bruton tyrosine kinase (BTK) inhibitor ibrutinib was the first and thus far only agent approved by the Food and Drug Administration for chronic GVHD. The approval was based on a single-arm, multicenter trial with 42 patients.

The ORR in this trial was 69%, consisting of 31% complete responses and 38% partial responses, with a duration of response longer than 10 months in slightly more than half of all patients. In all, 24% of patients had improvement of symptoms in two consecutive visits, and 29% continued on ibrutinib at the time of the primary analysis in 2017.

Based on these promising results, acalabrutinib, which is more potent and selective for BTK than ibrutinib, with no effect on either platelets or natural killer cells, is currently under investigation in a phase 2 trial in 50 patients at a dose of 100 mg orally twice daily.
 

JAK1/2 inhibition

The JAK1 inhibitor itacitinib failed to meet its primary ORR endpoint in the phase 3 GRAVITAS-301 study, according to a press release, but the manufacturer (Incyte) said that it is continuing its commitment to JAK inhibitors with ruxolitinib, which has shown activity against acute, steroid-refractory GVHD, and is being explored for prevention of chronic GVHD in the randomized, phase 3 REACH3 study.

The trial met its primary endpoint for a higher ORR at week 24 with ruxolitinib versus best available therapy, at 49.7% versus 25.6%, respectively, which translated into an odds ratio for response with the JAK inhibitor of 2.99 (P < .0001).
 

Selective T-cell expansion

Efavaleukin alfa is an IL-2-mutated protein (mutein), with a mutation in the IL-2RB-binding portion of IL-2 causing increased selectivity for regulatory T-cell expansion. It is bound to an IgG-Fc domain that is itself mutated, with reduced Fc receptor binding and IgG effector function to give it a longer half life. This agent is being studied in a phase 1/2 trial in a subcutaneous formulation delivered every 1 or 2 weeks to 68 patients.

Monocyte/macrophage depletion

Axatilimab is a high-affinity antibody targeting colony stimulating factor–1 receptor (CSF-1R) expressed on monocytes and macrophages. By blocking CSF-1R, it depletes circulation of nonclassical monocytes and prevents the differentiation and survival of M2 macrophages in tissue.

It is currently being investigated 30 patients in a phase 1/2 study in an intravenous formulation delivered over 30 minutes every 2-4 weeks.
 

Hedgehog pathway inhibition

There is evidence suggesting that hedgehog pathway inhibition can lessen fibrosis. Glasdegib (Daurismo) a potent selective oral inhibitor of the hedgehog signaling pathway, is approved for use with low-dose cytarabine for patients with newly diagnosed acute myeloid leukemia aged older than 75 years or have comorbidities precluding intensive chemotherapy.

This agent is associated with drug intolerance because of muscle spasms, dysgeusia, and alopecia, however.

The drug is currently in phase 1/2 at a dose of 50 mg orally per day in 20 patients.
 

ROCK2 inhibition

Belumosudil (formerly KD025) “appears to rebalance the immune system,” Dr. Lee said. Investigators think that the drug dampens an autoaggressive inflammatory response by selective inhibition of ROCK2.

This drug has been studied in a dose-escalation study and a phase 2 trial, in which 132 participants were randomized to receive belumosudil 200 mg either once or twice daily.

At a median follow-up of 8 months, the ORR with belumosudil 200 mg once and twice daily was 73% and 74%, respectively. Similar results were seen in patients who had previously received either ruxolitinib or ibrutinib. High response rates were seen in patients with severe chronic GVHD, involvement of four or more organs and a refractory response to their last line of therapy.
 

Hard-to-manage patients

“We’re very hopeful for many of these agents, but we have to acknowledge that there are still many management dilemmas, patients that we just don’t really know what to do with,” Dr. Lee said. “These include patients who have bad sclerosis and fasciitis, nonhealing skin ulcers, bronchiolitis obliterans, serositis that can be very difficult to manage, severe keratoconjunctivitis that can be eyesight threatening, nonhealing mouth ulcers, esophageal structures, and always patients who have frequent infections.

“We are hopeful that some these agents will be useful for our patients who have severe manifestations, but often the number of patients with these manifestations in the trials is too low to say something specific about them,” she added.
 

‘Exciting time’

“It’s an exciting time because there are a lot of different drugs that are being studied for chronic GVHD,” commented Betty Hamilton, MD, a hematologist/oncologist at the Cleveland Clinic.

“I think that where the field is going in terms of treatment is recognizing that chronic GVHD is a pretty heterogeneous disease, and we have to learn even more about the underlying biologic pathways to be able to determine which class of drugs to use and when,” she said in an interview.

She agreed with Dr. Lee that the goals of treating patients with chronic GVHD include improving symptoms and quality, preventing progression, ideally tapering patients off immunosuppression, and achieving a balance between preventing negative consequences of GVHD while maintain the benefits of a graft-versus-leukemia effect.

“In our center, drug choice is based on physician preference and comfort with how often they’ve used the drug, patients’ comorbidities, toxicities of the drug, and logistical considerations,” Dr. Hamilton said.

Dr. Lee disclosed consulting activities for Pfizer and Kadmon, travel and lodging from Amgen, and research funding from those companies and others. Dr. Hamilton disclosed consulting for Syndax and Incyte.

Despite improvements in prevention of graft-versus-host disease, chronic GVHD still occurs in 10%-50% of patients who undergo an allogeneic hematopoietic stem cell transplant, and these patients may require prolonged treatment with multiple lines of therapy, said a hematologist and transplant researcher.

“More effective, less toxic therapies for chronic GVHD are needed,” Stephanie Lee, MD, MPH, from the Fred Hutchinson Cancer Research Center in Seattle said at the Transplant & Cellular Therapies Meetings.

Dr. Lee reviewed clinical trials for chronic GVHD at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Although the incidence of chronic GVHD has gradually declined over the last 40 years and both relapse-free and overall survival following a chronic GVHD diagnosis have improved, “for patients who are diagnosed with chronic GVHD, they still will see many lines of therapy and many years of therapy,” she said.

Among 148 patients with chronic GVHD treated at her center, for example, 66% went on to two lines of therapy, 50% went on to three lines, 37% required four lines of therapy, and 20% needed five lines or more.

Salvage therapies for patients with chronic GVHD have evolved away from immunomodulators and immunosuppressants in the early 1990s, toward monoclonal antibodies such as rituximab in the early 2000s, to interleukin-2 and to tyrosine kinase inhibitors such as ruxolitinib (Jakafi) and ibrutinib (Imbruvica).

There are currently 36 agents that are FDA approved for at least one indication and can also be prescribed for the treatment of chronic GVHD, Dr. Lee noted.
 

Treatment goals

Dr. Lee laid out six goals for treating patients with chronic GVHD. They include:

• Controlling current signs and symptoms, measured by response rates and patient-reported outcomes
• Preventing further tissue and organ damage
• Minimizing toxicity
• Maintaining graft-versus-tumor effect
• Achieving graft tolerance and stopping immunosuppression
• Decreasing nonrelapse mortality and improving survival

Active trials

Dr. Lee identified 33 trials with chronic GVHD as an indication that are currently recruiting, and an additional 13 trials that are active but closed to recruiting. The trials can be generally grouped by mechanism of action, and involve agents targeting T-regulatory cells, B cells and/or B-cell receptor (BCR) signaling, monocytes/macrophages, costimulatory blockage, a proteasome inhibition, Janus kinase (JAK) 1/2 inhibitors, ROCK2 inhibitors, hedgehog pathway inhibition, cellular therapy, and organ-targeted therapy.

Most of the trials have overall response rate as the primary endpoint, and all but five are currently in phase 1 or 2. The currently active phase 3 trials include two with ibrutinib, one with the investigational agent itacitinib, one with ruxolitinib, and one with mesenchymal stem cells.

“I’ll note that, when results are reported, the denominator really matters for the overall response rate, especially if you’re talking about small trials, because if you require the patient to be treated with an agent for a certain period of time, and you take out all the people who didn’t make it to that time point, then your overall response rate looks better,” she said.
 

BTK inhibitors

The first-in-class Bruton tyrosine kinase (BTK) inhibitor ibrutinib was the first and thus far only agent approved by the Food and Drug Administration for chronic GVHD. The approval was based on a single-arm, multicenter trial with 42 patients.

The ORR in this trial was 69%, consisting of 31% complete responses and 38% partial responses, with a duration of response longer than 10 months in slightly more than half of all patients. In all, 24% of patients had improvement of symptoms in two consecutive visits, and 29% continued on ibrutinib at the time of the primary analysis in 2017.

Based on these promising results, acalabrutinib, which is more potent and selective for BTK than ibrutinib, with no effect on either platelets or natural killer cells, is currently under investigation in a phase 2 trial in 50 patients at a dose of 100 mg orally twice daily.
 

JAK1/2 inhibition

The JAK1 inhibitor itacitinib failed to meet its primary ORR endpoint in the phase 3 GRAVITAS-301 study, according to a press release, but the manufacturer (Incyte) said that it is continuing its commitment to JAK inhibitors with ruxolitinib, which has shown activity against acute, steroid-refractory GVHD, and is being explored for prevention of chronic GVHD in the randomized, phase 3 REACH3 study.

The trial met its primary endpoint for a higher ORR at week 24 with ruxolitinib versus best available therapy, at 49.7% versus 25.6%, respectively, which translated into an odds ratio for response with the JAK inhibitor of 2.99 (P < .0001).
 

Selective T-cell expansion

Efavaleukin alfa is an IL-2-mutated protein (mutein), with a mutation in the IL-2RB-binding portion of IL-2 causing increased selectivity for regulatory T-cell expansion. It is bound to an IgG-Fc domain that is itself mutated, with reduced Fc receptor binding and IgG effector function to give it a longer half life. This agent is being studied in a phase 1/2 trial in a subcutaneous formulation delivered every 1 or 2 weeks to 68 patients.

Monocyte/macrophage depletion

Axatilimab is a high-affinity antibody targeting colony stimulating factor–1 receptor (CSF-1R) expressed on monocytes and macrophages. By blocking CSF-1R, it depletes circulation of nonclassical monocytes and prevents the differentiation and survival of M2 macrophages in tissue.

It is currently being investigated 30 patients in a phase 1/2 study in an intravenous formulation delivered over 30 minutes every 2-4 weeks.
 

Hedgehog pathway inhibition

There is evidence suggesting that hedgehog pathway inhibition can lessen fibrosis. Glasdegib (Daurismo) a potent selective oral inhibitor of the hedgehog signaling pathway, is approved for use with low-dose cytarabine for patients with newly diagnosed acute myeloid leukemia aged older than 75 years or have comorbidities precluding intensive chemotherapy.

This agent is associated with drug intolerance because of muscle spasms, dysgeusia, and alopecia, however.

The drug is currently in phase 1/2 at a dose of 50 mg orally per day in 20 patients.
 

ROCK2 inhibition

Belumosudil (formerly KD025) “appears to rebalance the immune system,” Dr. Lee said. Investigators think that the drug dampens an autoaggressive inflammatory response by selective inhibition of ROCK2.

This drug has been studied in a dose-escalation study and a phase 2 trial, in which 132 participants were randomized to receive belumosudil 200 mg either once or twice daily.

At a median follow-up of 8 months, the ORR with belumosudil 200 mg once and twice daily was 73% and 74%, respectively. Similar results were seen in patients who had previously received either ruxolitinib or ibrutinib. High response rates were seen in patients with severe chronic GVHD, involvement of four or more organs and a refractory response to their last line of therapy.
 

Hard-to-manage patients

“We’re very hopeful for many of these agents, but we have to acknowledge that there are still many management dilemmas, patients that we just don’t really know what to do with,” Dr. Lee said. “These include patients who have bad sclerosis and fasciitis, nonhealing skin ulcers, bronchiolitis obliterans, serositis that can be very difficult to manage, severe keratoconjunctivitis that can be eyesight threatening, nonhealing mouth ulcers, esophageal structures, and always patients who have frequent infections.

“We are hopeful that some these agents will be useful for our patients who have severe manifestations, but often the number of patients with these manifestations in the trials is too low to say something specific about them,” she added.
 

‘Exciting time’

“It’s an exciting time because there are a lot of different drugs that are being studied for chronic GVHD,” commented Betty Hamilton, MD, a hematologist/oncologist at the Cleveland Clinic.

“I think that where the field is going in terms of treatment is recognizing that chronic GVHD is a pretty heterogeneous disease, and we have to learn even more about the underlying biologic pathways to be able to determine which class of drugs to use and when,” she said in an interview.

She agreed with Dr. Lee that the goals of treating patients with chronic GVHD include improving symptoms and quality, preventing progression, ideally tapering patients off immunosuppression, and achieving a balance between preventing negative consequences of GVHD while maintain the benefits of a graft-versus-leukemia effect.

“In our center, drug choice is based on physician preference and comfort with how often they’ve used the drug, patients’ comorbidities, toxicities of the drug, and logistical considerations,” Dr. Hamilton said.

Dr. Lee disclosed consulting activities for Pfizer and Kadmon, travel and lodging from Amgen, and research funding from those companies and others. Dr. Hamilton disclosed consulting for Syndax and Incyte.

The combination of lenvatinib and pembrolizumab outperforms sunitinib as first-line therapy for advanced clear-cell renal cell carcinoma (RCC), based on findings of the CLEAR trial.

Courtesy of Memorial Sloan Kettering Cancer Center

Results from the phase 3 trial were reported at the 2021 Genitourinary Cancers Symposium (Abstract 269) and simultaneously published in the New England Journal of Medicine.

Early-phase trials have shown the promise of targeting RCC from two angles, with both antiangiogenic therapy and immunotherapy, said presenter Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center, New York.

The CLEAR trial was designed to compare monotherapy with sunitinib to treatment with lenvatinib plus either pembrolizumab or everolimus.

The risk of progression-free survival events was 61% lower with lenvatinib-pembrolizumab and 35% lower with lenvatinib-everolimus, compared with sunitinib. However, only the first combination significantly reduced the risk of death.

Treatment-related adverse events were more common with both combinations but manageable with dose modifications.

“These results support lenvatinib plus pembrolizumab as a potential first-line treatment for patients with advanced RCC,” Dr. Motzer said.

Oncologists will likely soon have a handful of first-line options from which to choose, he acknowledged.

“It is a great situation, that we have made such progress in RCC with IO [immuno-oncology] therapy in the first line with ipilimumab-nivolumab, and now with the IO-TKI [tyrosine kinase inhibitor] combinations,” Dr. Motzer said.

The choice will probably come down to personal preference, experience with the various combinations, and side effect profiles, he speculated.

“I will say, however, that the data with lenvatinib-pembrolizumab is very impressive in terms of the long progression-free survival, in terms of the doubling of response rate to over 70%, in terms of the 16% complete response rate,” he said.
 

Trial details

The CLEAR investigators evenly randomized 1,069 patients with advanced clear-cell RCC who had not received prior systemic therapy to treatment with lenvatinib-pembrolizumab, lenvatinib-everolimus, or sunitinib.

The primary analysis was conducted at a median follow-up of 27 months.

The median progression-free survival was 9.2 months with sunitinib, 23.9 months with lenvatinib-pembrolizumab (hazard ratio, 0.39; P < .001), and 14.7 months with lenvatinib-everolimus (HR for events, 0.65; P < .001).

Findings were similar across key subgroups, including International Metastatic RCC Database Consortium risk groups.

An interim analysis of overall survival showed that patients lived significantly longer with lenvatinib-pembrolizumab versus sunitinib (HR, 0.66; P = .005), with similar benefit across subgroups, except for the favorable risk group.

In contrast, lenvatinib-everolimus did not significantly improve overall survival (HR, 1.15; P = .3). The median overall survival was not reached in any treatment arm.

“To me, this emphasizes the role of IO therapy combinations in the first line. I think you need the IO in the first line to get the dramatic efficacy results that we saw in the CLEAR study,” Dr. Motzer said.

The confirmed objective response rate was 36.1% with sunitinib, 71.0% with lenvatinib-pembrolizumab (relative risk, 1.97; P < .001), and 53.5% with lenvatinib-everolimus (RR, 1.48; P <.001). The median duration of response was 14.6 months, 25.8 months, and 16.6 months, respectively.

Grade 3 or higher treatment-related adverse events occurred in 58.8% of patients in the sunitinib group, 71.6% of the lenvatinib-pembrolizumab group, and 73.0% of the lenvatinib-everolimus group. The higher rates with the combinations likely reflected longer treatment durations, according to Dr. Motzer.

The most common grade 3 or higher events with lenvatinib-pembrolizumab were hypertension (25.3%), diarrhea (8.2%), and proteinuria (7.4%). The most common grade 3 or higher events with lenvatinib-everolimus were hypertension (20.8%), hypertriglyceridemia (10.1%), and diarrhea (9.6%).

“The relatively low rates of hepatic toxicity, lack of myelosuppression, and low rate of high-grade hand-foot syndrome is an attractive feature for lenvatinib in combination,” Dr. Motzer said.
 

Which combination, which sequence?

“Lenvatinib plus pembrolizumab is another novel combination to have in our armamentarium now for first-line clear-cell RCC,” said invited discussant Stephanie A. Berg, DO, of Loyola University Medical Center in Maywood, Ill.

Courtesy of Loyola University

CLEAR is the fourth positive trial of combination tyrosine kinase inhibitor therapy and immunotherapy in this setting, although findings and study populations differ somewhat, and longer follow-up is needed, she said.

“None of these combinations have been directly compared to one another, and I don’t believe they will be compared head to head,” Dr. Berg said. “But other characteristics – for example, health-related quality of life, familiarity of the agents for clinicians, and high tumor burden versus slow-growing disease – may become important to choose the best first-line option for our patients.”

The emerging first-line options also raise some questions about the optimal sequencing of agents, according to Dr. Berg.

“If one starts with combination immunotherapy, it becomes an automatic choice to use a VEGF tyrosine kinase inhibitor second line,” she elaborated. “These trials establish that immuno-oncology–tyrosine kinase inhibitor combination therapy is now standard of care, but our second-line choice is less clear. Therefore, data is needed on the most suitable order of therapy for the entire population, as well as specific groups in the future.”

The CLEAR trial was sponsored by Eisai Inc. and Merck Sharp & Dohme Corp. Dr. Motzer disclosed relationships with Eisai, Merck, and many other companies. Dr. Berg disclosed a consulting or advisory role with Bristol-Myers Squibb.

The combination of lenvatinib and pembrolizumab outperforms sunitinib as first-line therapy for advanced clear-cell renal cell carcinoma (RCC), based on findings of the CLEAR trial.

Courtesy of Memorial Sloan Kettering Cancer Center

Results from the phase 3 trial were reported at the 2021 Genitourinary Cancers Symposium (Abstract 269) and simultaneously published in the New England Journal of Medicine.

Early-phase trials have shown the promise of targeting RCC from two angles, with both antiangiogenic therapy and immunotherapy, said presenter Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center, New York.

The CLEAR trial was designed to compare monotherapy with sunitinib to treatment with lenvatinib plus either pembrolizumab or everolimus.

The risk of progression-free survival events was 61% lower with lenvatinib-pembrolizumab and 35% lower with lenvatinib-everolimus, compared with sunitinib. However, only the first combination significantly reduced the risk of death.

Treatment-related adverse events were more common with both combinations but manageable with dose modifications.

“These results support lenvatinib plus pembrolizumab as a potential first-line treatment for patients with advanced RCC,” Dr. Motzer said.

Oncologists will likely soon have a handful of first-line options from which to choose, he acknowledged.

“It is a great situation, that we have made such progress in RCC with IO [immuno-oncology] therapy in the first line with ipilimumab-nivolumab, and now with the IO-TKI [tyrosine kinase inhibitor] combinations,” Dr. Motzer said.

The choice will probably come down to personal preference, experience with the various combinations, and side effect profiles, he speculated.

“I will say, however, that the data with lenvatinib-pembrolizumab is very impressive in terms of the long progression-free survival, in terms of the doubling of response rate to over 70%, in terms of the 16% complete response rate,” he said.
 

Trial details

The CLEAR investigators evenly randomized 1,069 patients with advanced clear-cell RCC who had not received prior systemic therapy to treatment with lenvatinib-pembrolizumab, lenvatinib-everolimus, or sunitinib.

The primary analysis was conducted at a median follow-up of 27 months.

The median progression-free survival was 9.2 months with sunitinib, 23.9 months with lenvatinib-pembrolizumab (hazard ratio, 0.39; P < .001), and 14.7 months with lenvatinib-everolimus (HR for events, 0.65; P < .001).

Findings were similar across key subgroups, including International Metastatic RCC Database Consortium risk groups.

An interim analysis of overall survival showed that patients lived significantly longer with lenvatinib-pembrolizumab versus sunitinib (HR, 0.66; P = .005), with similar benefit across subgroups, except for the favorable risk group.

In contrast, lenvatinib-everolimus did not significantly improve overall survival (HR, 1.15; P = .3). The median overall survival was not reached in any treatment arm.

“To me, this emphasizes the role of IO therapy combinations in the first line. I think you need the IO in the first line to get the dramatic efficacy results that we saw in the CLEAR study,” Dr. Motzer said.

The confirmed objective response rate was 36.1% with sunitinib, 71.0% with lenvatinib-pembrolizumab (relative risk, 1.97; P < .001), and 53.5% with lenvatinib-everolimus (RR, 1.48; P <.001). The median duration of response was 14.6 months, 25.8 months, and 16.6 months, respectively.

Grade 3 or higher treatment-related adverse events occurred in 58.8% of patients in the sunitinib group, 71.6% of the lenvatinib-pembrolizumab group, and 73.0% of the lenvatinib-everolimus group. The higher rates with the combinations likely reflected longer treatment durations, according to Dr. Motzer.

The most common grade 3 or higher events with lenvatinib-pembrolizumab were hypertension (25.3%), diarrhea (8.2%), and proteinuria (7.4%). The most common grade 3 or higher events with lenvatinib-everolimus were hypertension (20.8%), hypertriglyceridemia (10.1%), and diarrhea (9.6%).

“The relatively low rates of hepatic toxicity, lack of myelosuppression, and low rate of high-grade hand-foot syndrome is an attractive feature for lenvatinib in combination,” Dr. Motzer said.
 

Which combination, which sequence?

“Lenvatinib plus pembrolizumab is another novel combination to have in our armamentarium now for first-line clear-cell RCC,” said invited discussant Stephanie A. Berg, DO, of Loyola University Medical Center in Maywood, Ill.

Courtesy of Loyola University

CLEAR is the fourth positive trial of combination tyrosine kinase inhibitor therapy and immunotherapy in this setting, although findings and study populations differ somewhat, and longer follow-up is needed, she said.

“None of these combinations have been directly compared to one another, and I don’t believe they will be compared head to head,” Dr. Berg said. “But other characteristics – for example, health-related quality of life, familiarity of the agents for clinicians, and high tumor burden versus slow-growing disease – may become important to choose the best first-line option for our patients.”

The emerging first-line options also raise some questions about the optimal sequencing of agents, according to Dr. Berg.

“If one starts with combination immunotherapy, it becomes an automatic choice to use a VEGF tyrosine kinase inhibitor second line,” she elaborated. “These trials establish that immuno-oncology–tyrosine kinase inhibitor combination therapy is now standard of care, but our second-line choice is less clear. Therefore, data is needed on the most suitable order of therapy for the entire population, as well as specific groups in the future.”

The CLEAR trial was sponsored by Eisai Inc. and Merck Sharp & Dohme Corp. Dr. Motzer disclosed relationships with Eisai, Merck, and many other companies. Dr. Berg disclosed a consulting or advisory role with Bristol-Myers Squibb.

The combination of lenvatinib and pembrolizumab outperforms sunitinib as first-line therapy for advanced clear-cell renal cell carcinoma (RCC), based on findings of the CLEAR trial.

Courtesy of Memorial Sloan Kettering Cancer Center

Results from the phase 3 trial were reported at the 2021 Genitourinary Cancers Symposium (Abstract 269) and simultaneously published in the New England Journal of Medicine.

Early-phase trials have shown the promise of targeting RCC from two angles, with both antiangiogenic therapy and immunotherapy, said presenter Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center, New York.

The CLEAR trial was designed to compare monotherapy with sunitinib to treatment with lenvatinib plus either pembrolizumab or everolimus.

The risk of progression-free survival events was 61% lower with lenvatinib-pembrolizumab and 35% lower with lenvatinib-everolimus, compared with sunitinib. However, only the first combination significantly reduced the risk of death.

Treatment-related adverse events were more common with both combinations but manageable with dose modifications.

“These results support lenvatinib plus pembrolizumab as a potential first-line treatment for patients with advanced RCC,” Dr. Motzer said.

Oncologists will likely soon have a handful of first-line options from which to choose, he acknowledged.

“It is a great situation, that we have made such progress in RCC with IO [immuno-oncology] therapy in the first line with ipilimumab-nivolumab, and now with the IO-TKI [tyrosine kinase inhibitor] combinations,” Dr. Motzer said.

The choice will probably come down to personal preference, experience with the various combinations, and side effect profiles, he speculated.

“I will say, however, that the data with lenvatinib-pembrolizumab is very impressive in terms of the long progression-free survival, in terms of the doubling of response rate to over 70%, in terms of the 16% complete response rate,” he said.
 

Trial details

The CLEAR investigators evenly randomized 1,069 patients with advanced clear-cell RCC who had not received prior systemic therapy to treatment with lenvatinib-pembrolizumab, lenvatinib-everolimus, or sunitinib.

The primary analysis was conducted at a median follow-up of 27 months.

The median progression-free survival was 9.2 months with sunitinib, 23.9 months with lenvatinib-pembrolizumab (hazard ratio, 0.39; P < .001), and 14.7 months with lenvatinib-everolimus (HR for events, 0.65; P < .001).

Findings were similar across key subgroups, including International Metastatic RCC Database Consortium risk groups.

An interim analysis of overall survival showed that patients lived significantly longer with lenvatinib-pembrolizumab versus sunitinib (HR, 0.66; P = .005), with similar benefit across subgroups, except for the favorable risk group.

In contrast, lenvatinib-everolimus did not significantly improve overall survival (HR, 1.15; P = .3). The median overall survival was not reached in any treatment arm.

“To me, this emphasizes the role of IO therapy combinations in the first line. I think you need the IO in the first line to get the dramatic efficacy results that we saw in the CLEAR study,” Dr. Motzer said.

The confirmed objective response rate was 36.1% with sunitinib, 71.0% with lenvatinib-pembrolizumab (relative risk, 1.97; P < .001), and 53.5% with lenvatinib-everolimus (RR, 1.48; P <.001). The median duration of response was 14.6 months, 25.8 months, and 16.6 months, respectively.

Grade 3 or higher treatment-related adverse events occurred in 58.8% of patients in the sunitinib group, 71.6% of the lenvatinib-pembrolizumab group, and 73.0% of the lenvatinib-everolimus group. The higher rates with the combinations likely reflected longer treatment durations, according to Dr. Motzer.

The most common grade 3 or higher events with lenvatinib-pembrolizumab were hypertension (25.3%), diarrhea (8.2%), and proteinuria (7.4%). The most common grade 3 or higher events with lenvatinib-everolimus were hypertension (20.8%), hypertriglyceridemia (10.1%), and diarrhea (9.6%).

“The relatively low rates of hepatic toxicity, lack of myelosuppression, and low rate of high-grade hand-foot syndrome is an attractive feature for lenvatinib in combination,” Dr. Motzer said.
 

Which combination, which sequence?

“Lenvatinib plus pembrolizumab is another novel combination to have in our armamentarium now for first-line clear-cell RCC,” said invited discussant Stephanie A. Berg, DO, of Loyola University Medical Center in Maywood, Ill.

Courtesy of Loyola University

CLEAR is the fourth positive trial of combination tyrosine kinase inhibitor therapy and immunotherapy in this setting, although findings and study populations differ somewhat, and longer follow-up is needed, she said.

“None of these combinations have been directly compared to one another, and I don’t believe they will be compared head to head,” Dr. Berg said. “But other characteristics – for example, health-related quality of life, familiarity of the agents for clinicians, and high tumor burden versus slow-growing disease – may become important to choose the best first-line option for our patients.”

The emerging first-line options also raise some questions about the optimal sequencing of agents, according to Dr. Berg.

“If one starts with combination immunotherapy, it becomes an automatic choice to use a VEGF tyrosine kinase inhibitor second line,” she elaborated. “These trials establish that immuno-oncology–tyrosine kinase inhibitor combination therapy is now standard of care, but our second-line choice is less clear. Therefore, data is needed on the most suitable order of therapy for the entire population, as well as specific groups in the future.”

The CLEAR trial was sponsored by Eisai Inc. and Merck Sharp & Dohme Corp. Dr. Motzer disclosed relationships with Eisai, Merck, and many other companies. Dr. Berg disclosed a consulting or advisory role with Bristol-Myers Squibb.

The potent anabolic, antiosteoporosis agent romosozumab has been saddled with an Food and Drug Administration–mandated black-box warning for increased cardiovascular risk that may not be warranted, Glenn Haugeberg, MD, PhD, asserted at the 2021 Rheumatology Winter Clinical Symposium.

ogichobanov/iStock/Getty Images Plus

The black-box warning states that romosozumab (Evenity), a monoclonal antibody approved in 2019 for fracture prevention in patients with osteoporosis, may increase the risk of MI, stroke, and cardiovascular death. The warning arose from FDA concerns raised by the results of the phase 3 ARCH trial in which 4,093 postmenopausal women at high fracture risk were randomized to monthly subcutaneous injections of romosozumab or weekly dosing of the oral bisphosphonate alendronate (Fosamax) for 1 year, followed by 12 months of open-label alendronate for all. Alarm bells went off at the FDA because during year 1, the incidence of adjudicated major adverse cardiovascular events was 2.5% in the romosozumab arm, compared with 1.9% with alendronate.
 

Could a cardioprotective effect of bisphosphonates explain cardiovascular concerns?

However, evidence from multiple animal and human studies suggests that bisphosphonates actually have a cardioprotective effect. For example, a Taiwanese population-based cohort study of 1,548 patients on bisphosphonate therapy for osteoporotic fractures and 4,644 individuals with hip or vertebral fractures who were not on a bisphosphonate showed a 65% reduction in the risk of acute MI during 2 years of follow-up in those who received a bisphosphonate.

“That may explain the ARCH finding. It may – I say may – be that this concern in the ARCH study can be explained by the positive effect of the bisphosphonates on cardiovascular events,” according to Dr. Haugeberg, head of the division of rheumatology at the Southern Norway Hospital Trust, Kristiansand, and professor of medicine at the Norwegian University of Science and Technology, Trondheim.

He noted that, in the FRAME trial, another pivotal phase 3 trial of romosozumab, there was no signal of increased cardiovascular risk, compared with placebo. In FRAME, which included 7,180 osteoporotic postmenopausal women, rates of major adverse cardiovascular events and other adverse events were balanced between the two study arms at 12 months. Indeed, the incidence of adjudicated serious cardiovascular events was 0.5% with romosozumab and 0.4% with placebo injections. After 12 months, all participants were transitioned to denosumab (Prolia) for another 12 months. At 24 months, there remained no significant between-group difference in cardiovascular events, cancer, osteoarthritis, hyperostosis, or other major adverse events.
 

Potency of romosozumab

Romosozumab’s efficacy for fracture prevention in these two pivotal trials was striking. The risk of new vertebral fractures was reduced by 73% with romosozumab, compared with placebo at 12 months in FRAME, and by 75% at 24 months in the romosozumab-to-denosumab group.

“FRAME was a 12-month study for the primary endpoint. The bisphosphonate studies typically had a 3-year design in order to show benefit, but here you see only 12-month follow-up. This illustrates the potency of this drug. We saw rapid increase in bone density and a huge decrease in new vertebral fractures versus placebo in the first 12 months, then during follow-up with denosumab the reduction in fractures was maintained,” the rheumatologist commented.

In the ARCH trial, where romosozumab went head to head with a very effective oral bisphosphonate, the risk of new vertebral fractures was 48% lower at 24 months in the romosozumab-to-alendronate group than in women on alendronate for the full 24 months, while the risk of hip fractures was reduced by 38%.

Romosozumab is a humanized monoclonal antibody with a novel mechanism of anabolic action: This agent binds to sclerostin, which is produced in osteocytes. When sclerostin binds to receptors on osteoblasts it reduces their activity, thereby inhibiting bone formation. Romosozumab takes away this inhibition of osteoblasts, boosting their activity. The result is increased bone formation accompanied by decreased bone resorption. This allows for a logical treatment approach: first using an anabolic agent – in this instance, subcutaneously injected romosozumab at 210 mg once monthly for 12 months – then switching to an antiresorptive agent in order to maintain the gain in bone mineral density and decrease fracture risk. This is the same treatment strategy recommended when using the anabolic agents teriparatide (Forteo) and abaloparatide (Tymlos); however, those parathyroid hormone and parathyroid hormone–related protein analogs are seldom used in Norway because their cost is substantially greater than for romosozumab, he explained.

Updated Endocrine Society guidelines

Dr. Haugeberg called romosozumab “a new and wonderful drug.” The Endocrine Society also considers romosozumab an important new drug, as evidenced by the release of an 8-page update of the group’s clinical practice guideline on the pharmacologic management of osteoporosis in postmenopausal women; the update was devoted specifically to the use of romosozumab. The update, published in response to the biologic’s recent approval by U.S., Canadian, and European regulatory agencies, came just 10 months after release of the Endocrine Society’s comprehensive 28-page clinical practice guideline.

Dr. Haugeberg is a fan of the Endocrine Society guideline, which recommends romosozumab as a first-line therapy in postmenopausal women at very high risk of osteoporotic fracture, defined as those with a history of multiple vertebral fractures or severe osteoporosis with a T score of –2.5 or less at the hip or spine plus fractures. The updated guideline also recommends consideration of the antisclerostin biologic in high-risk patients who have failed on antiresorptive treatments.

The practice guideline states that the issue of a possible cardioprotective effect of alendronate in the ARCH trial “remains uncertain at this time.”

“Women at high risk of cardiovascular disease and stroke should not be considered for romosozumab pending further studies on cardiovascular risk associated with this treatment,” according to the Endocrine Society.

Dr. Haugeberg reported receiving research grants from Pfizer and Biogen and serving as a consultant to and/or on speakers’ bureaus for Amgen, which markets romosozumab, and more than a dozen other pharmaceutical companies.

bjancin@mdedge.com

The potent anabolic, antiosteoporosis agent romosozumab has been saddled with an Food and Drug Administration–mandated black-box warning for increased cardiovascular risk that may not be warranted, Glenn Haugeberg, MD, PhD, asserted at the 2021 Rheumatology Winter Clinical Symposium.

ogichobanov/iStock/Getty Images Plus

The black-box warning states that romosozumab (Evenity), a monoclonal antibody approved in 2019 for fracture prevention in patients with osteoporosis, may increase the risk of MI, stroke, and cardiovascular death. The warning arose from FDA concerns raised by the results of the phase 3 ARCH trial in which 4,093 postmenopausal women at high fracture risk were randomized to monthly subcutaneous injections of romosozumab or weekly dosing of the oral bisphosphonate alendronate (Fosamax) for 1 year, followed by 12 months of open-label alendronate for all. Alarm bells went off at the FDA because during year 1, the incidence of adjudicated major adverse cardiovascular events was 2.5% in the romosozumab arm, compared with 1.9% with alendronate.
 

Could a cardioprotective effect of bisphosphonates explain cardiovascular concerns?

However, evidence from multiple animal and human studies suggests that bisphosphonates actually have a cardioprotective effect. For example, a Taiwanese population-based cohort study of 1,548 patients on bisphosphonate therapy for osteoporotic fractures and 4,644 individuals with hip or vertebral fractures who were not on a bisphosphonate showed a 65% reduction in the risk of acute MI during 2 years of follow-up in those who received a bisphosphonate.

“That may explain the ARCH finding. It may – I say may – be that this concern in the ARCH study can be explained by the positive effect of the bisphosphonates on cardiovascular events,” according to Dr. Haugeberg, head of the division of rheumatology at the Southern Norway Hospital Trust, Kristiansand, and professor of medicine at the Norwegian University of Science and Technology, Trondheim.

He noted that, in the FRAME trial, another pivotal phase 3 trial of romosozumab, there was no signal of increased cardiovascular risk, compared with placebo. In FRAME, which included 7,180 osteoporotic postmenopausal women, rates of major adverse cardiovascular events and other adverse events were balanced between the two study arms at 12 months. Indeed, the incidence of adjudicated serious cardiovascular events was 0.5% with romosozumab and 0.4% with placebo injections. After 12 months, all participants were transitioned to denosumab (Prolia) for another 12 months. At 24 months, there remained no significant between-group difference in cardiovascular events, cancer, osteoarthritis, hyperostosis, or other major adverse events.
 

Potency of romosozumab

Romosozumab’s efficacy for fracture prevention in these two pivotal trials was striking. The risk of new vertebral fractures was reduced by 73% with romosozumab, compared with placebo at 12 months in FRAME, and by 75% at 24 months in the romosozumab-to-denosumab group.

“FRAME was a 12-month study for the primary endpoint. The bisphosphonate studies typically had a 3-year design in order to show benefit, but here you see only 12-month follow-up. This illustrates the potency of this drug. We saw rapid increase in bone density and a huge decrease in new vertebral fractures versus placebo in the first 12 months, then during follow-up with denosumab the reduction in fractures was maintained,” the rheumatologist commented.

In the ARCH trial, where romosozumab went head to head with a very effective oral bisphosphonate, the risk of new vertebral fractures was 48% lower at 24 months in the romosozumab-to-alendronate group than in women on alendronate for the full 24 months, while the risk of hip fractures was reduced by 38%.

Romosozumab is a humanized monoclonal antibody with a novel mechanism of anabolic action: This agent binds to sclerostin, which is produced in osteocytes. When sclerostin binds to receptors on osteoblasts it reduces their activity, thereby inhibiting bone formation. Romosozumab takes away this inhibition of osteoblasts, boosting their activity. The result is increased bone formation accompanied by decreased bone resorption. This allows for a logical treatment approach: first using an anabolic agent – in this instance, subcutaneously injected romosozumab at 210 mg once monthly for 12 months – then switching to an antiresorptive agent in order to maintain the gain in bone mineral density and decrease fracture risk. This is the same treatment strategy recommended when using the anabolic agents teriparatide (Forteo) and abaloparatide (Tymlos); however, those parathyroid hormone and parathyroid hormone–related protein analogs are seldom used in Norway because their cost is substantially greater than for romosozumab, he explained.

Updated Endocrine Society guidelines

Dr. Haugeberg called romosozumab “a new and wonderful drug.” The Endocrine Society also considers romosozumab an important new drug, as evidenced by the release of an 8-page update of the group’s clinical practice guideline on the pharmacologic management of osteoporosis in postmenopausal women; the update was devoted specifically to the use of romosozumab. The update, published in response to the biologic’s recent approval by U.S., Canadian, and European regulatory agencies, came just 10 months after release of the Endocrine Society’s comprehensive 28-page clinical practice guideline.

Dr. Haugeberg is a fan of the Endocrine Society guideline, which recommends romosozumab as a first-line therapy in postmenopausal women at very high risk of osteoporotic fracture, defined as those with a history of multiple vertebral fractures or severe osteoporosis with a T score of –2.5 or less at the hip or spine plus fractures. The updated guideline also recommends consideration of the antisclerostin biologic in high-risk patients who have failed on antiresorptive treatments.

The practice guideline states that the issue of a possible cardioprotective effect of alendronate in the ARCH trial “remains uncertain at this time.”

“Women at high risk of cardiovascular disease and stroke should not be considered for romosozumab pending further studies on cardiovascular risk associated with this treatment,” according to the Endocrine Society.

Dr. Haugeberg reported receiving research grants from Pfizer and Biogen and serving as a consultant to and/or on speakers’ bureaus for Amgen, which markets romosozumab, and more than a dozen other pharmaceutical companies.

bjancin@mdedge.com

The potent anabolic, antiosteoporosis agent romosozumab has been saddled with an Food and Drug Administration–mandated black-box warning for increased cardiovascular risk that may not be warranted, Glenn Haugeberg, MD, PhD, asserted at the 2021 Rheumatology Winter Clinical Symposium.

ogichobanov/iStock/Getty Images Plus

The black-box warning states that romosozumab (Evenity), a monoclonal antibody approved in 2019 for fracture prevention in patients with osteoporosis, may increase the risk of MI, stroke, and cardiovascular death. The warning arose from FDA concerns raised by the results of the phase 3 ARCH trial in which 4,093 postmenopausal women at high fracture risk were randomized to monthly subcutaneous injections of romosozumab or weekly dosing of the oral bisphosphonate alendronate (Fosamax) for 1 year, followed by 12 months of open-label alendronate for all. Alarm bells went off at the FDA because during year 1, the incidence of adjudicated major adverse cardiovascular events was 2.5% in the romosozumab arm, compared with 1.9% with alendronate.
 

Could a cardioprotective effect of bisphosphonates explain cardiovascular concerns?

However, evidence from multiple animal and human studies suggests that bisphosphonates actually have a cardioprotective effect. For example, a Taiwanese population-based cohort study of 1,548 patients on bisphosphonate therapy for osteoporotic fractures and 4,644 individuals with hip or vertebral fractures who were not on a bisphosphonate showed a 65% reduction in the risk of acute MI during 2 years of follow-up in those who received a bisphosphonate.

“That may explain the ARCH finding. It may – I say may – be that this concern in the ARCH study can be explained by the positive effect of the bisphosphonates on cardiovascular events,” according to Dr. Haugeberg, head of the division of rheumatology at the Southern Norway Hospital Trust, Kristiansand, and professor of medicine at the Norwegian University of Science and Technology, Trondheim.

He noted that, in the FRAME trial, another pivotal phase 3 trial of romosozumab, there was no signal of increased cardiovascular risk, compared with placebo. In FRAME, which included 7,180 osteoporotic postmenopausal women, rates of major adverse cardiovascular events and other adverse events were balanced between the two study arms at 12 months. Indeed, the incidence of adjudicated serious cardiovascular events was 0.5% with romosozumab and 0.4% with placebo injections. After 12 months, all participants were transitioned to denosumab (Prolia) for another 12 months. At 24 months, there remained no significant between-group difference in cardiovascular events, cancer, osteoarthritis, hyperostosis, or other major adverse events.
 

Potency of romosozumab

Romosozumab’s efficacy for fracture prevention in these two pivotal trials was striking. The risk of new vertebral fractures was reduced by 73% with romosozumab, compared with placebo at 12 months in FRAME, and by 75% at 24 months in the romosozumab-to-denosumab group.

“FRAME was a 12-month study for the primary endpoint. The bisphosphonate studies typically had a 3-year design in order to show benefit, but here you see only 12-month follow-up. This illustrates the potency of this drug. We saw rapid increase in bone density and a huge decrease in new vertebral fractures versus placebo in the first 12 months, then during follow-up with denosumab the reduction in fractures was maintained,” the rheumatologist commented.

In the ARCH trial, where romosozumab went head to head with a very effective oral bisphosphonate, the risk of new vertebral fractures was 48% lower at 24 months in the romosozumab-to-alendronate group than in women on alendronate for the full 24 months, while the risk of hip fractures was reduced by 38%.

Romosozumab is a humanized monoclonal antibody with a novel mechanism of anabolic action: This agent binds to sclerostin, which is produced in osteocytes. When sclerostin binds to receptors on osteoblasts it reduces their activity, thereby inhibiting bone formation. Romosozumab takes away this inhibition of osteoblasts, boosting their activity. The result is increased bone formation accompanied by decreased bone resorption. This allows for a logical treatment approach: first using an anabolic agent – in this instance, subcutaneously injected romosozumab at 210 mg once monthly for 12 months – then switching to an antiresorptive agent in order to maintain the gain in bone mineral density and decrease fracture risk. This is the same treatment strategy recommended when using the anabolic agents teriparatide (Forteo) and abaloparatide (Tymlos); however, those parathyroid hormone and parathyroid hormone–related protein analogs are seldom used in Norway because their cost is substantially greater than for romosozumab, he explained.

Updated Endocrine Society guidelines

Dr. Haugeberg called romosozumab “a new and wonderful drug.” The Endocrine Society also considers romosozumab an important new drug, as evidenced by the release of an 8-page update of the group’s clinical practice guideline on the pharmacologic management of osteoporosis in postmenopausal women; the update was devoted specifically to the use of romosozumab. The update, published in response to the biologic’s recent approval by U.S., Canadian, and European regulatory agencies, came just 10 months after release of the Endocrine Society’s comprehensive 28-page clinical practice guideline.

Dr. Haugeberg is a fan of the Endocrine Society guideline, which recommends romosozumab as a first-line therapy in postmenopausal women at very high risk of osteoporotic fracture, defined as those with a history of multiple vertebral fractures or severe osteoporosis with a T score of –2.5 or less at the hip or spine plus fractures. The updated guideline also recommends consideration of the antisclerostin biologic in high-risk patients who have failed on antiresorptive treatments.

The practice guideline states that the issue of a possible cardioprotective effect of alendronate in the ARCH trial “remains uncertain at this time.”

“Women at high risk of cardiovascular disease and stroke should not be considered for romosozumab pending further studies on cardiovascular risk associated with this treatment,” according to the Endocrine Society.

Dr. Haugeberg reported receiving research grants from Pfizer and Biogen and serving as a consultant to and/or on speakers’ bureaus for Amgen, which markets romosozumab, and more than a dozen other pharmaceutical companies.

bjancin@mdedge.com

Home-based subcutaneous immune globulin therapy is a promising alternative to intravenous immune globulin therapy for patients with refractory dermatomyositis or polymyositis, Anna Postolova, MD, MPH, declared at the 2021 Rheumatology Winter Clinical Symposium.

“This is really exciting. I think in the years to come we may see a change to having our patients be able to do immune globulin therapy at home,” said Dr. Postolova, a rheumatologist and allergist/immunologist at Stanford (Calif.) Health Care.

“The technology is there. I think our patients might feel more comfortable getting immune globulin at home,” she said. “I would love to switch more patients from IVIg to SCIg [subcutaneous immune globulin] in my practice.”

A few caveats: SCIg remains off label for treatment of dermatomyositis (DM) or polymyositis (PM). Its approved indication is as replacement therapy in patients with primary or secondary immunodeficiency diseases. IVIg is approved for this indication, but is also approved for DM/PM refractory to high-dose corticosteroids and immunosuppressants. Yet SCIg is clearly effective for these autoimmune inflammatory diseases, albeit to date the supporting evidence comes chiefly from observational studies and anecdotal experience.

“I don’t know if insurers will cover it, but they should because it’s obviously a lot cheaper to do it at home,” she noted.
 

SCIg advantages

SCIg offers compelling advantages over IVIg in addition to its substantially lower cost. These include far fewer systemic side effects, shorter infusion time, greater bioavailability, and better quality of life. Patients self-administer SCIg at home, avoiding the inconvenience of IVIg therapy, which entails travel time for once-monthly hospitalization or long hours spent in an infusion center, she explained.

French investigators recently documented a previously unappreciated further advantage of home-based SCIg. They convened a focus group of patients with DM or PM experienced with both IVIg and home SCIg and determined that participants uniformly preferred home SCIg. The patients cited a new and welcome feeling of autonomy and control.

“All patients with experience of IVIg and SCIg expressed a clear preference for SCIg, which was described to be easy, less disruptive for daily life, well tolerated, and less time-consuming. Preference was mainly related to a restoration of autonomy. Home-based self-administration reinforced the feeling of independence,” according to the investigators.
 

Available products

Six preparations of SCIg are commercially available. Most are in 10% concentration, as are all IVIg products. However, a 20% formulation of SCIg known as Hizentra allows for a smaller infusion volume and quicker completion of a treatment session. And one SCIg product, HyQvia, uses recombinant human hyaluronidase-facilitated 10% immune globulin, allowing home infusion of large volumes of sustained-release immune globulin on a once-monthly basis.

The relatively recent introduction of home SCIg for treatment of autoimmune inflammatory diseases, including DM, PM, and chronic inflammatory demyelinating polyneuropathy, has been pioneered mainly by European investigators. The treatment is often given by programmable mechanical pump once weekly. Italian investigators have reported efficacy in DM using 0.2 g/kg per week, which is about half the monthly total dose of IVIg employed. The infusion rate is 10-40 mL/hour, with a volume of around 35 mL per injection site.

Alternatively, SCIg can be delivered by rapid push infusions of smaller volumes with a syringe two or three times per week; that’s the regimen that was used at 2 g/kg over the course of a month by patients in the French focus group study, who didn’t mind the more frequent dosing.

“As they have had severe long-lasting symptoms, SCIg was perceived as a curative rather than a preventive therapy,” according to the French investigators.

More than 40% of patients experience adverse reactions to IVIg. These often involve headaches, nausea, back or abdominal pain, arthralgias, and/or difficulty breathing. Thromboembolic events and acute renal failure occur occasionally. For this reason, many physicians give a prophylactic dose of corticosteroids an hour before a patient’s first dose of IVIg. These systemic side effects are so rare with SCIg that Dr. Postolova has never pretreated with steroids, even though the main reason she resorts to the home therapy is a patient’s track record of poor tolerance of IVIg. The lower abdomen and thigh are the most commonly used subcutaneous infusion sites. Mild local infusion site reactions are fairly common.

Formulating IVIg and SCIg is a complex process that entails plasma procurement and pooling, fractionation, and purification. It takes 10,000-60,000 plasma donations to make one lot of IVIg. Donations are accepted only from repeated donors. Samples are held for 6 months and tested for infectious agents. However, efforts are underway to develop bioengineered recombinant immune globulin products that don’t require donated plasma. These products are being designed to capture and enhance the most important mechanisms of benefit of plasma-derived immunoglobulins using Fc fragments that target key receptors, rather than relying on full-length immune globulin. The goal is enhanced efficacy at much lower doses than with IVIg or SCIg.

Dr. Postolova reported having no financial conflicts regarding her presentation.

bjancin@mdedge.com

Home-based subcutaneous immune globulin therapy is a promising alternative to intravenous immune globulin therapy for patients with refractory dermatomyositis or polymyositis, Anna Postolova, MD, MPH, declared at the 2021 Rheumatology Winter Clinical Symposium.

“This is really exciting. I think in the years to come we may see a change to having our patients be able to do immune globulin therapy at home,” said Dr. Postolova, a rheumatologist and allergist/immunologist at Stanford (Calif.) Health Care.

“The technology is there. I think our patients might feel more comfortable getting immune globulin at home,” she said. “I would love to switch more patients from IVIg to SCIg [subcutaneous immune globulin] in my practice.”

A few caveats: SCIg remains off label for treatment of dermatomyositis (DM) or polymyositis (PM). Its approved indication is as replacement therapy in patients with primary or secondary immunodeficiency diseases. IVIg is approved for this indication, but is also approved for DM/PM refractory to high-dose corticosteroids and immunosuppressants. Yet SCIg is clearly effective for these autoimmune inflammatory diseases, albeit to date the supporting evidence comes chiefly from observational studies and anecdotal experience.

“I don’t know if insurers will cover it, but they should because it’s obviously a lot cheaper to do it at home,” she noted.
 

SCIg advantages

SCIg offers compelling advantages over IVIg in addition to its substantially lower cost. These include far fewer systemic side effects, shorter infusion time, greater bioavailability, and better quality of life. Patients self-administer SCIg at home, avoiding the inconvenience of IVIg therapy, which entails travel time for once-monthly hospitalization or long hours spent in an infusion center, she explained.

French investigators recently documented a previously unappreciated further advantage of home-based SCIg. They convened a focus group of patients with DM or PM experienced with both IVIg and home SCIg and determined that participants uniformly preferred home SCIg. The patients cited a new and welcome feeling of autonomy and control.

“All patients with experience of IVIg and SCIg expressed a clear preference for SCIg, which was described to be easy, less disruptive for daily life, well tolerated, and less time-consuming. Preference was mainly related to a restoration of autonomy. Home-based self-administration reinforced the feeling of independence,” according to the investigators.
 

Available products

Six preparations of SCIg are commercially available. Most are in 10% concentration, as are all IVIg products. However, a 20% formulation of SCIg known as Hizentra allows for a smaller infusion volume and quicker completion of a treatment session. And one SCIg product, HyQvia, uses recombinant human hyaluronidase-facilitated 10% immune globulin, allowing home infusion of large volumes of sustained-release immune globulin on a once-monthly basis.

The relatively recent introduction of home SCIg for treatment of autoimmune inflammatory diseases, including DM, PM, and chronic inflammatory demyelinating polyneuropathy, has been pioneered mainly by European investigators. The treatment is often given by programmable mechanical pump once weekly. Italian investigators have reported efficacy in DM using 0.2 g/kg per week, which is about half the monthly total dose of IVIg employed. The infusion rate is 10-40 mL/hour, with a volume of around 35 mL per injection site.

Alternatively, SCIg can be delivered by rapid push infusions of smaller volumes with a syringe two or three times per week; that’s the regimen that was used at 2 g/kg over the course of a month by patients in the French focus group study, who didn’t mind the more frequent dosing.

“As they have had severe long-lasting symptoms, SCIg was perceived as a curative rather than a preventive therapy,” according to the French investigators.

More than 40% of patients experience adverse reactions to IVIg. These often involve headaches, nausea, back or abdominal pain, arthralgias, and/or difficulty breathing. Thromboembolic events and acute renal failure occur occasionally. For this reason, many physicians give a prophylactic dose of corticosteroids an hour before a patient’s first dose of IVIg. These systemic side effects are so rare with SCIg that Dr. Postolova has never pretreated with steroids, even though the main reason she resorts to the home therapy is a patient’s track record of poor tolerance of IVIg. The lower abdomen and thigh are the most commonly used subcutaneous infusion sites. Mild local infusion site reactions are fairly common.

Formulating IVIg and SCIg is a complex process that entails plasma procurement and pooling, fractionation, and purification. It takes 10,000-60,000 plasma donations to make one lot of IVIg. Donations are accepted only from repeated donors. Samples are held for 6 months and tested for infectious agents. However, efforts are underway to develop bioengineered recombinant immune globulin products that don’t require donated plasma. These products are being designed to capture and enhance the most important mechanisms of benefit of plasma-derived immunoglobulins using Fc fragments that target key receptors, rather than relying on full-length immune globulin. The goal is enhanced efficacy at much lower doses than with IVIg or SCIg.

Dr. Postolova reported having no financial conflicts regarding her presentation.

bjancin@mdedge.com

Home-based subcutaneous immune globulin therapy is a promising alternative to intravenous immune globulin therapy for patients with refractory dermatomyositis or polymyositis, Anna Postolova, MD, MPH, declared at the 2021 Rheumatology Winter Clinical Symposium.

“This is really exciting. I think in the years to come we may see a change to having our patients be able to do immune globulin therapy at home,” said Dr. Postolova, a rheumatologist and allergist/immunologist at Stanford (Calif.) Health Care.

“The technology is there. I think our patients might feel more comfortable getting immune globulin at home,” she said. “I would love to switch more patients from IVIg to SCIg [subcutaneous immune globulin] in my practice.”

A few caveats: SCIg remains off label for treatment of dermatomyositis (DM) or polymyositis (PM). Its approved indication is as replacement therapy in patients with primary or secondary immunodeficiency diseases. IVIg is approved for this indication, but is also approved for DM/PM refractory to high-dose corticosteroids and immunosuppressants. Yet SCIg is clearly effective for these autoimmune inflammatory diseases, albeit to date the supporting evidence comes chiefly from observational studies and anecdotal experience.

“I don’t know if insurers will cover it, but they should because it’s obviously a lot cheaper to do it at home,” she noted.
 

SCIg advantages

SCIg offers compelling advantages over IVIg in addition to its substantially lower cost. These include far fewer systemic side effects, shorter infusion time, greater bioavailability, and better quality of life. Patients self-administer SCIg at home, avoiding the inconvenience of IVIg therapy, which entails travel time for once-monthly hospitalization or long hours spent in an infusion center, she explained.

French investigators recently documented a previously unappreciated further advantage of home-based SCIg. They convened a focus group of patients with DM or PM experienced with both IVIg and home SCIg and determined that participants uniformly preferred home SCIg. The patients cited a new and welcome feeling of autonomy and control.

“All patients with experience of IVIg and SCIg expressed a clear preference for SCIg, which was described to be easy, less disruptive for daily life, well tolerated, and less time-consuming. Preference was mainly related to a restoration of autonomy. Home-based self-administration reinforced the feeling of independence,” according to the investigators.
 

Available products

Six preparations of SCIg are commercially available. Most are in 10% concentration, as are all IVIg products. However, a 20% formulation of SCIg known as Hizentra allows for a smaller infusion volume and quicker completion of a treatment session. And one SCIg product, HyQvia, uses recombinant human hyaluronidase-facilitated 10% immune globulin, allowing home infusion of large volumes of sustained-release immune globulin on a once-monthly basis.

The relatively recent introduction of home SCIg for treatment of autoimmune inflammatory diseases, including DM, PM, and chronic inflammatory demyelinating polyneuropathy, has been pioneered mainly by European investigators. The treatment is often given by programmable mechanical pump once weekly. Italian investigators have reported efficacy in DM using 0.2 g/kg per week, which is about half the monthly total dose of IVIg employed. The infusion rate is 10-40 mL/hour, with a volume of around 35 mL per injection site.

Alternatively, SCIg can be delivered by rapid push infusions of smaller volumes with a syringe two or three times per week; that’s the regimen that was used at 2 g/kg over the course of a month by patients in the French focus group study, who didn’t mind the more frequent dosing.

“As they have had severe long-lasting symptoms, SCIg was perceived as a curative rather than a preventive therapy,” according to the French investigators.

More than 40% of patients experience adverse reactions to IVIg. These often involve headaches, nausea, back or abdominal pain, arthralgias, and/or difficulty breathing. Thromboembolic events and acute renal failure occur occasionally. For this reason, many physicians give a prophylactic dose of corticosteroids an hour before a patient’s first dose of IVIg. These systemic side effects are so rare with SCIg that Dr. Postolova has never pretreated with steroids, even though the main reason she resorts to the home therapy is a patient’s track record of poor tolerance of IVIg. The lower abdomen and thigh are the most commonly used subcutaneous infusion sites. Mild local infusion site reactions are fairly common.

Formulating IVIg and SCIg is a complex process that entails plasma procurement and pooling, fractionation, and purification. It takes 10,000-60,000 plasma donations to make one lot of IVIg. Donations are accepted only from repeated donors. Samples are held for 6 months and tested for infectious agents. However, efforts are underway to develop bioengineered recombinant immune globulin products that don’t require donated plasma. These products are being designed to capture and enhance the most important mechanisms of benefit of plasma-derived immunoglobulins using Fc fragments that target key receptors, rather than relying on full-length immune globulin. The goal is enhanced efficacy at much lower doses than with IVIg or SCIg.

Dr. Postolova reported having no financial conflicts regarding her presentation.

bjancin@mdedge.com