SAN DIEGO – Among patients presenting to the emergency department with suicidal ideation, the number of previous psychiatric admissions is the most important predictor of a subsequent suicide attempt, results from a 2-year-long study showed.

Doug Brunk/MDedge News

Momentary measures – significant current difficulties with sleep, energy, or appetite, and anhedonia – “are important considerations during suicide risk assessment, regardless of whether the patient meets the threshold for major depressive disorder, lead study author Anne C. Knorr said in an interview in advance of the annual meeting of the American College of Emergency Physicians.

“Many traditionally studied psychiatric risk factors do not significantly differ between individuals who think about suicide and those who act on their suicidal thoughts, an important distinction as only one-third of those who think about suicide carry out a suicide attempt. While there is support for some psychiatric factors – for example, anxiety, substance use disorders, sleep disturbance – being useful in differentiating these groups, the current study is unique in its use of a longitudinal design to identify influential risk factors that predict future suicide attempt among those with suicidal ideation,” she said.

Ms. Knorr, a research project manager at Geisinger Medical Center, Danville, Pa., and her colleagues collected electronic medical record data from 908 patients who had received a psychiatric evaluation at an index emergency department visit for suicidal ideation over a 2-year period. The mean age of patients was 39 years. The target sample was 30 patients who had returned to the ED following a suicide attempt within 6 months of their index ED visit.

The researchers analyzed 32 predictor variables from patient charts, including demographics, psychiatric history, and current psychiatric presentation. The evaluation was done with “a machine learning statistical approach which is more capable than traditional statistical approaches in handling a large number of predictor variables,” Ms. Knorr said.

The number of previous psychiatric admissions was the most important predictor of a subsequent suicide attempt. The next nine most important variables were sleep disturbance, history of family suicide, low energy, patient age, psychiatrist determination of severe suicide risk, psychiatrist determination of moderate suicide risk, appetite issues, presence of a support system, and loss of interest/pleasure.

These symptoms may not typically be weighed heavily in risk assessments, Ms. Knorr said. “Additionally, given that research suggests that the clinical determination of suicide risk is historically poor, it was interesting that psychiatrist determination of moderate or high risk was influential in predicting a return visit for suicide attempt. Finally, we were surprised that a past history of suicide attempt, often viewed as the strongest predictor of a future suicide attempt, did not emerge as one of the top 10 influential predictors.

“Limitations of this study include the use of a return visit to a Geisinger emergency department as the only measure of a future suicide attempt and the utilization of data from only one health system,” she noted.

The study was funded by the Geisinger Clinic Research Fund. One of the coauthors, Andrei Nemoianu, MD, reported receipt of a research grant from Takeda Pharmaceuticals for a separate study.

dbrunk@mdedge.com

SOURCE: Knorr A et al. Ann Emerg Med. 2018 Oct;72;4:S23. doi. 10.1016/j.annemergmed.2018.08.055.

SAN DIEGO – Among patients presenting to the emergency department with suicidal ideation, the number of previous psychiatric admissions is the most important predictor of a subsequent suicide attempt, results from a 2-year-long study showed.

Doug Brunk/MDedge News

Momentary measures – significant current difficulties with sleep, energy, or appetite, and anhedonia – “are important considerations during suicide risk assessment, regardless of whether the patient meets the threshold for major depressive disorder, lead study author Anne C. Knorr said in an interview in advance of the annual meeting of the American College of Emergency Physicians.

“Many traditionally studied psychiatric risk factors do not significantly differ between individuals who think about suicide and those who act on their suicidal thoughts, an important distinction as only one-third of those who think about suicide carry out a suicide attempt. While there is support for some psychiatric factors – for example, anxiety, substance use disorders, sleep disturbance – being useful in differentiating these groups, the current study is unique in its use of a longitudinal design to identify influential risk factors that predict future suicide attempt among those with suicidal ideation,” she said.

Ms. Knorr, a research project manager at Geisinger Medical Center, Danville, Pa., and her colleagues collected electronic medical record data from 908 patients who had received a psychiatric evaluation at an index emergency department visit for suicidal ideation over a 2-year period. The mean age of patients was 39 years. The target sample was 30 patients who had returned to the ED following a suicide attempt within 6 months of their index ED visit.

The researchers analyzed 32 predictor variables from patient charts, including demographics, psychiatric history, and current psychiatric presentation. The evaluation was done with “a machine learning statistical approach which is more capable than traditional statistical approaches in handling a large number of predictor variables,” Ms. Knorr said.

The number of previous psychiatric admissions was the most important predictor of a subsequent suicide attempt. The next nine most important variables were sleep disturbance, history of family suicide, low energy, patient age, psychiatrist determination of severe suicide risk, psychiatrist determination of moderate suicide risk, appetite issues, presence of a support system, and loss of interest/pleasure.

These symptoms may not typically be weighed heavily in risk assessments, Ms. Knorr said. “Additionally, given that research suggests that the clinical determination of suicide risk is historically poor, it was interesting that psychiatrist determination of moderate or high risk was influential in predicting a return visit for suicide attempt. Finally, we were surprised that a past history of suicide attempt, often viewed as the strongest predictor of a future suicide attempt, did not emerge as one of the top 10 influential predictors.

“Limitations of this study include the use of a return visit to a Geisinger emergency department as the only measure of a future suicide attempt and the utilization of data from only one health system,” she noted.

The study was funded by the Geisinger Clinic Research Fund. One of the coauthors, Andrei Nemoianu, MD, reported receipt of a research grant from Takeda Pharmaceuticals for a separate study.

dbrunk@mdedge.com

SOURCE: Knorr A et al. Ann Emerg Med. 2018 Oct;72;4:S23. doi. 10.1016/j.annemergmed.2018.08.055.

SAN DIEGO – Among patients presenting to the emergency department with suicidal ideation, the number of previous psychiatric admissions is the most important predictor of a subsequent suicide attempt, results from a 2-year-long study showed.

Doug Brunk/MDedge News

Momentary measures – significant current difficulties with sleep, energy, or appetite, and anhedonia – “are important considerations during suicide risk assessment, regardless of whether the patient meets the threshold for major depressive disorder, lead study author Anne C. Knorr said in an interview in advance of the annual meeting of the American College of Emergency Physicians.

“Many traditionally studied psychiatric risk factors do not significantly differ between individuals who think about suicide and those who act on their suicidal thoughts, an important distinction as only one-third of those who think about suicide carry out a suicide attempt. While there is support for some psychiatric factors – for example, anxiety, substance use disorders, sleep disturbance – being useful in differentiating these groups, the current study is unique in its use of a longitudinal design to identify influential risk factors that predict future suicide attempt among those with suicidal ideation,” she said.

Ms. Knorr, a research project manager at Geisinger Medical Center, Danville, Pa., and her colleagues collected electronic medical record data from 908 patients who had received a psychiatric evaluation at an index emergency department visit for suicidal ideation over a 2-year period. The mean age of patients was 39 years. The target sample was 30 patients who had returned to the ED following a suicide attempt within 6 months of their index ED visit.

The researchers analyzed 32 predictor variables from patient charts, including demographics, psychiatric history, and current psychiatric presentation. The evaluation was done with “a machine learning statistical approach which is more capable than traditional statistical approaches in handling a large number of predictor variables,” Ms. Knorr said.

The number of previous psychiatric admissions was the most important predictor of a subsequent suicide attempt. The next nine most important variables were sleep disturbance, history of family suicide, low energy, patient age, psychiatrist determination of severe suicide risk, psychiatrist determination of moderate suicide risk, appetite issues, presence of a support system, and loss of interest/pleasure.

These symptoms may not typically be weighed heavily in risk assessments, Ms. Knorr said. “Additionally, given that research suggests that the clinical determination of suicide risk is historically poor, it was interesting that psychiatrist determination of moderate or high risk was influential in predicting a return visit for suicide attempt. Finally, we were surprised that a past history of suicide attempt, often viewed as the strongest predictor of a future suicide attempt, did not emerge as one of the top 10 influential predictors.

“Limitations of this study include the use of a return visit to a Geisinger emergency department as the only measure of a future suicide attempt and the utilization of data from only one health system,” she noted.

The study was funded by the Geisinger Clinic Research Fund. One of the coauthors, Andrei Nemoianu, MD, reported receipt of a research grant from Takeda Pharmaceuticals for a separate study.

dbrunk@mdedge.com

SOURCE: Knorr A et al. Ann Emerg Med. 2018 Oct;72;4:S23. doi. 10.1016/j.annemergmed.2018.08.055.

Clinical question: Does patient experience correlate with specific hospital care coordination and transition strategies, and if so, which strategies most strongly correlate with higher patient experience scores?

Background: Patient experience is an increasingly important measure in value-based payment programs. However, progress has been slow in improving patient experience, and little empirical data exist regarding which strategies are effective. Care transitions are critical times during a hospitalization, with many hospitals already implementing measures to improve the discharge process and prevent readmission of patients. It is not known whether those measures also influence patient experience scores, and if they do improve scores, which measures are most effective at doing so.

Study design: An analytic observational survey design.

Setting: Hospitals eligible for the Hospital Readmissions Reduction Program (HRRP) between June 2013 and December 2014.

Synopsis: A survey was developed and given to chief medical officers at 1,600 hospitals between June 2013 and December 2014; the survey assessed care coordination strategies employed by these institutions. 992 hospitals (62% response rate) were subsequently categorized as “low-strategy,” “mid-strategy,” or “high-strategy” hospitals. Patient satisfaction scores from the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey in 2014 were correlated to the number of strategies and the specific strategies each hospital employed. In general, the higher-strategy hospitals had significantly higher HCAHPS survey scores than did low-strategy hospitals (+2.23 points; P less than .001). Specifically, creating and sharing a discharge summary prior to discharge (+1.43 points; P less than .001), using a discharge planner (+1.71 points; P less than .001), and calling patients 48 hours post discharge (+1.64 points; P less than .001) all resulted in overall higher hospital ratings by patients.
 

One limitation of this study is that no causal inference can be made between the specific strategies associated with higher HCAHPS scores and care coordination strategies.

Bottom line: Hospital-led care transition strategies with direct patient interactions led to higher patient satisfaction scores.

Citation: Figueroa JF et al. Hospital-level care coordination strategies associated with better patient experience. BMJ Qual Saf. 2018 Apr 4. doi: 10.1136/bmjqs-2017-007597.

Dr. Tsien is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.

Clinical question: Does patient experience correlate with specific hospital care coordination and transition strategies, and if so, which strategies most strongly correlate with higher patient experience scores?

Background: Patient experience is an increasingly important measure in value-based payment programs. However, progress has been slow in improving patient experience, and little empirical data exist regarding which strategies are effective. Care transitions are critical times during a hospitalization, with many hospitals already implementing measures to improve the discharge process and prevent readmission of patients. It is not known whether those measures also influence patient experience scores, and if they do improve scores, which measures are most effective at doing so.

Study design: An analytic observational survey design.

Setting: Hospitals eligible for the Hospital Readmissions Reduction Program (HRRP) between June 2013 and December 2014.

Synopsis: A survey was developed and given to chief medical officers at 1,600 hospitals between June 2013 and December 2014; the survey assessed care coordination strategies employed by these institutions. 992 hospitals (62% response rate) were subsequently categorized as “low-strategy,” “mid-strategy,” or “high-strategy” hospitals. Patient satisfaction scores from the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey in 2014 were correlated to the number of strategies and the specific strategies each hospital employed. In general, the higher-strategy hospitals had significantly higher HCAHPS survey scores than did low-strategy hospitals (+2.23 points; P less than .001). Specifically, creating and sharing a discharge summary prior to discharge (+1.43 points; P less than .001), using a discharge planner (+1.71 points; P less than .001), and calling patients 48 hours post discharge (+1.64 points; P less than .001) all resulted in overall higher hospital ratings by patients.
 

One limitation of this study is that no causal inference can be made between the specific strategies associated with higher HCAHPS scores and care coordination strategies.

Bottom line: Hospital-led care transition strategies with direct patient interactions led to higher patient satisfaction scores.

Citation: Figueroa JF et al. Hospital-level care coordination strategies associated with better patient experience. BMJ Qual Saf. 2018 Apr 4. doi: 10.1136/bmjqs-2017-007597.

Dr. Tsien is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.

Clinical question: Does patient experience correlate with specific hospital care coordination and transition strategies, and if so, which strategies most strongly correlate with higher patient experience scores?

Background: Patient experience is an increasingly important measure in value-based payment programs. However, progress has been slow in improving patient experience, and little empirical data exist regarding which strategies are effective. Care transitions are critical times during a hospitalization, with many hospitals already implementing measures to improve the discharge process and prevent readmission of patients. It is not known whether those measures also influence patient experience scores, and if they do improve scores, which measures are most effective at doing so.

Study design: An analytic observational survey design.

Setting: Hospitals eligible for the Hospital Readmissions Reduction Program (HRRP) between June 2013 and December 2014.

Synopsis: A survey was developed and given to chief medical officers at 1,600 hospitals between June 2013 and December 2014; the survey assessed care coordination strategies employed by these institutions. 992 hospitals (62% response rate) were subsequently categorized as “low-strategy,” “mid-strategy,” or “high-strategy” hospitals. Patient satisfaction scores from the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey in 2014 were correlated to the number of strategies and the specific strategies each hospital employed. In general, the higher-strategy hospitals had significantly higher HCAHPS survey scores than did low-strategy hospitals (+2.23 points; P less than .001). Specifically, creating and sharing a discharge summary prior to discharge (+1.43 points; P less than .001), using a discharge planner (+1.71 points; P less than .001), and calling patients 48 hours post discharge (+1.64 points; P less than .001) all resulted in overall higher hospital ratings by patients.
 

One limitation of this study is that no causal inference can be made between the specific strategies associated with higher HCAHPS scores and care coordination strategies.

Bottom line: Hospital-led care transition strategies with direct patient interactions led to higher patient satisfaction scores.

Citation: Figueroa JF et al. Hospital-level care coordination strategies associated with better patient experience. BMJ Qual Saf. 2018 Apr 4. doi: 10.1136/bmjqs-2017-007597.

Dr. Tsien is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.

Resource

US Preventive Services Task Force. Screening for cervical cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018;320:674-686. https://jamanetwork.com/journals/jama/fullarticle/2697704. Accessed September 14, 2018.

Resource

US Preventive Services Task Force. Screening for cervical cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018;320:674-686. https://jamanetwork.com/journals/jama/fullarticle/2697704. Accessed September 14, 2018.

Resource

US Preventive Services Task Force. Screening for cervical cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018;320:674-686. https://jamanetwork.com/journals/jama/fullarticle/2697704. Accessed September 14, 2018.

SAN DIEGO – Clinical outcomes were better when stent placement was guided by intravascular ultrasound rather than angiography, based on the results of a trial conducted in China. Unlike previous comparative studies, which focused on patients with more complex lesions, this trial included all patients undergoing drug-eluting stent (DES) placement.

In the ULTIMATE trial, 1,448 all-comer patients receiving DES were randomized to either intravascular ultrasound (IVUS)–guided or angiography-guided implantation, reported Junjie Zhang, PhD, of Nanjing Medical University in China, and colleagues. The study excluded patients who had a life expectancy shorter than 12 months, who were intolerant of dual antiplatelet therapy, and who had severe calcification needing rotational atherectomy.

At 30 days after stent placement, the incidence of target vessel failure was 0.8% in the IVUS group and 1.9% in the angiography group, a nonsignificant trend. However, outcomes were significantly different at 1 year, with target vessel failure occurring in 2.9% of IVUS patients and 5.4% of angiography patients (hazard ratio, 0.530; 95% confidence interval, 0.312-0.901; P = .019).

The work was simultaneously published in the Journal of the American College of Cardiology (2018 Sept. doi: 10.1016/j.jacc.2018.09.013) .

Despite good results in this and prior studies, uptake of the IVUS procedure is not high in the United States or Europe, according to members of a panel that reviewed the results at the Transcatheter Cardiovascular Therapeutics annual meeting.

“How can people continue to ignore the importance of imaging-guided stent optimization? Even with second-generation DES, the results are consistent across the studies. This is just another piece of irrefutable evidence,” said Gary S. Mintz, MD, chief medical officer at the Cardiovascular Research Foundation, and a discussant at the meeting, sponsored by the Cardiovascular Research Foundation.

Jim Kling/MDedge News

SAN DIEGO – Clinical outcomes were better when stent placement was guided by intravascular ultrasound rather than angiography, based on the results of a trial conducted in China. Unlike previous comparative studies, which focused on patients with more complex lesions, this trial included all patients undergoing drug-eluting stent (DES) placement.

In the ULTIMATE trial, 1,448 all-comer patients receiving DES were randomized to either intravascular ultrasound (IVUS)–guided or angiography-guided implantation, reported Junjie Zhang, PhD, of Nanjing Medical University in China, and colleagues. The study excluded patients who had a life expectancy shorter than 12 months, who were intolerant of dual antiplatelet therapy, and who had severe calcification needing rotational atherectomy.

At 30 days after stent placement, the incidence of target vessel failure was 0.8% in the IVUS group and 1.9% in the angiography group, a nonsignificant trend. However, outcomes were significantly different at 1 year, with target vessel failure occurring in 2.9% of IVUS patients and 5.4% of angiography patients (hazard ratio, 0.530; 95% confidence interval, 0.312-0.901; P = .019).

The work was simultaneously published in the Journal of the American College of Cardiology (2018 Sept. doi: 10.1016/j.jacc.2018.09.013) .

Despite good results in this and prior studies, uptake of the IVUS procedure is not high in the United States or Europe, according to members of a panel that reviewed the results at the Transcatheter Cardiovascular Therapeutics annual meeting.

“How can people continue to ignore the importance of imaging-guided stent optimization? Even with second-generation DES, the results are consistent across the studies. This is just another piece of irrefutable evidence,” said Gary S. Mintz, MD, chief medical officer at the Cardiovascular Research Foundation, and a discussant at the meeting, sponsored by the Cardiovascular Research Foundation.

Jim Kling/MDedge News

SAN DIEGO – Clinical outcomes were better when stent placement was guided by intravascular ultrasound rather than angiography, based on the results of a trial conducted in China. Unlike previous comparative studies, which focused on patients with more complex lesions, this trial included all patients undergoing drug-eluting stent (DES) placement.

In the ULTIMATE trial, 1,448 all-comer patients receiving DES were randomized to either intravascular ultrasound (IVUS)–guided or angiography-guided implantation, reported Junjie Zhang, PhD, of Nanjing Medical University in China, and colleagues. The study excluded patients who had a life expectancy shorter than 12 months, who were intolerant of dual antiplatelet therapy, and who had severe calcification needing rotational atherectomy.

At 30 days after stent placement, the incidence of target vessel failure was 0.8% in the IVUS group and 1.9% in the angiography group, a nonsignificant trend. However, outcomes were significantly different at 1 year, with target vessel failure occurring in 2.9% of IVUS patients and 5.4% of angiography patients (hazard ratio, 0.530; 95% confidence interval, 0.312-0.901; P = .019).

The work was simultaneously published in the Journal of the American College of Cardiology (2018 Sept. doi: 10.1016/j.jacc.2018.09.013) .

Despite good results in this and prior studies, uptake of the IVUS procedure is not high in the United States or Europe, according to members of a panel that reviewed the results at the Transcatheter Cardiovascular Therapeutics annual meeting.

“How can people continue to ignore the importance of imaging-guided stent optimization? Even with second-generation DES, the results are consistent across the studies. This is just another piece of irrefutable evidence,” said Gary S. Mintz, MD, chief medical officer at the Cardiovascular Research Foundation, and a discussant at the meeting, sponsored by the Cardiovascular Research Foundation.

Jim Kling/MDedge News

Interruptions of patients’ refills for combination inhaled corticosteroid medication caused by the Medicare Part D formulary switch may have resulted in increased exacerbations and hospitalizations, according to a study that will be presented at the CHEST 2018 annual meeting.

Katie Devane, PhD, and her colleagues examined pharmacy records of 44,832 patients aged 12 years and older who had received a combination inhaled corticosteroid (budesonide/formoterol) and a long-acting beta-agonist medication in 2016-2017. They were followed to track their refills, medication switches, and use of other medications such as oral corticosteroids, antibiotics, and rescue inhalers.

After the Medicare Part D formulary switch on Jan. 1, 2017, many of these patients experienced disruption of their refills. About half of the patients attempted to get a refill of their inhaled corticosteroid prescription but only 46% were approved. One-third of the patients studied did not replace their medication, 12% switched to monotherapy, and 17% had no inhaled medication, the study found.

The investigators concluded that the formulary block resulted in many patients going without optimal medication and potentially led to more exacerbations and ER visits.

View the study abstract here: https://journal.chestnet.org/article/S0012-3692(18)31877-4/fulltext

The study will be presented in the session Improving Care in COPD, Monday, Oct. 8, 2:15 p.m., Convention Center Room 207A.

Interruptions of patients’ refills for combination inhaled corticosteroid medication caused by the Medicare Part D formulary switch may have resulted in increased exacerbations and hospitalizations, according to a study that will be presented at the CHEST 2018 annual meeting.

Katie Devane, PhD, and her colleagues examined pharmacy records of 44,832 patients aged 12 years and older who had received a combination inhaled corticosteroid (budesonide/formoterol) and a long-acting beta-agonist medication in 2016-2017. They were followed to track their refills, medication switches, and use of other medications such as oral corticosteroids, antibiotics, and rescue inhalers.

After the Medicare Part D formulary switch on Jan. 1, 2017, many of these patients experienced disruption of their refills. About half of the patients attempted to get a refill of their inhaled corticosteroid prescription but only 46% were approved. One-third of the patients studied did not replace their medication, 12% switched to monotherapy, and 17% had no inhaled medication, the study found.

The investigators concluded that the formulary block resulted in many patients going without optimal medication and potentially led to more exacerbations and ER visits.

View the study abstract here: https://journal.chestnet.org/article/S0012-3692(18)31877-4/fulltext

The study will be presented in the session Improving Care in COPD, Monday, Oct. 8, 2:15 p.m., Convention Center Room 207A.

Interruptions of patients’ refills for combination inhaled corticosteroid medication caused by the Medicare Part D formulary switch may have resulted in increased exacerbations and hospitalizations, according to a study that will be presented at the CHEST 2018 annual meeting.

Katie Devane, PhD, and her colleagues examined pharmacy records of 44,832 patients aged 12 years and older who had received a combination inhaled corticosteroid (budesonide/formoterol) and a long-acting beta-agonist medication in 2016-2017. They were followed to track their refills, medication switches, and use of other medications such as oral corticosteroids, antibiotics, and rescue inhalers.

After the Medicare Part D formulary switch on Jan. 1, 2017, many of these patients experienced disruption of their refills. About half of the patients attempted to get a refill of their inhaled corticosteroid prescription but only 46% were approved. One-third of the patients studied did not replace their medication, 12% switched to monotherapy, and 17% had no inhaled medication, the study found.

The investigators concluded that the formulary block resulted in many patients going without optimal medication and potentially led to more exacerbations and ER visits.

View the study abstract here: https://journal.chestnet.org/article/S0012-3692(18)31877-4/fulltext

The study will be presented in the session Improving Care in COPD, Monday, Oct. 8, 2:15 p.m., Convention Center Room 207A.

Children with asthma who are provided with care and medication per National Asthma Education and Prevention Program guidelines can improve over time, despite the presence of environmental factors such as second-hand tobacco smoke and domestic pets, according to a study presented at the CHEST 2018 annual meeting.

A study conducted at the Nationwide Children’s Hospital in Columbus, Ohio, included 395 children aged 2-17 years with a diagnosis of uncontrolled asthma. These children were then treated using the NAEPP guidelines for acute care needs and symptom control. In this sample of patients, 25% were exposed to second-hand smoke, and 55% had a cat or dog in the home.

The investigators followed these patients and observed improvement of symptoms. But in a comparison of those with and without the potentially problematic environmental factors, improvement was independent of the presence of these factors. The findings suggest that NAEPP-recommended treatment of asthma is more important than are some environmental factors.

View the study abstract here: https://journal.chestnet.org/article/S0012-3692(18)31862-2/fulltext.

The findings will be presented in the session on Obstructive Lung Diseases, Wednesday, Oct. 10, at 1:00 p.m.
 

Children with asthma who are provided with care and medication per National Asthma Education and Prevention Program guidelines can improve over time, despite the presence of environmental factors such as second-hand tobacco smoke and domestic pets, according to a study presented at the CHEST 2018 annual meeting.

A study conducted at the Nationwide Children’s Hospital in Columbus, Ohio, included 395 children aged 2-17 years with a diagnosis of uncontrolled asthma. These children were then treated using the NAEPP guidelines for acute care needs and symptom control. In this sample of patients, 25% were exposed to second-hand smoke, and 55% had a cat or dog in the home.

The investigators followed these patients and observed improvement of symptoms. But in a comparison of those with and without the potentially problematic environmental factors, improvement was independent of the presence of these factors. The findings suggest that NAEPP-recommended treatment of asthma is more important than are some environmental factors.

View the study abstract here: https://journal.chestnet.org/article/S0012-3692(18)31862-2/fulltext.

The findings will be presented in the session on Obstructive Lung Diseases, Wednesday, Oct. 10, at 1:00 p.m.
 

Children with asthma who are provided with care and medication per National Asthma Education and Prevention Program guidelines can improve over time, despite the presence of environmental factors such as second-hand tobacco smoke and domestic pets, according to a study presented at the CHEST 2018 annual meeting.

A study conducted at the Nationwide Children’s Hospital in Columbus, Ohio, included 395 children aged 2-17 years with a diagnosis of uncontrolled asthma. These children were then treated using the NAEPP guidelines for acute care needs and symptom control. In this sample of patients, 25% were exposed to second-hand smoke, and 55% had a cat or dog in the home.

The investigators followed these patients and observed improvement of symptoms. But in a comparison of those with and without the potentially problematic environmental factors, improvement was independent of the presence of these factors. The findings suggest that NAEPP-recommended treatment of asthma is more important than are some environmental factors.

View the study abstract here: https://journal.chestnet.org/article/S0012-3692(18)31862-2/fulltext.

The findings will be presented in the session on Obstructive Lung Diseases, Wednesday, Oct. 10, at 1:00 p.m.
 

Former smokers’ adherence to annual follow-up screening for lung cancer was found to be less than optimal, according to a study to be presented at the CHEST 2018 annual meeting.

Paul B. Brasher, MD, and his colleagues from the Thoracic Oncology Research Group at the Medical University of South Carolina in Charleston studied adherence to recommended low-dose computed tomography (LDCT) among Veterans Affairs patients who were at high risk for lung cancer and whose baseline LDCTs were negative.

A total of 2,106 veterans aged 55-80 years who had at least a 30-pack year smoking history were initially screened within the Veterans Health Administration Lung Cancer Screening Demonstration Project. The study tracked 1,120 of these patients for 18 months to determine their adherence to annual LDCT screening; the rate of adherence was 77.6%.

View the abstract here: https://journal.chestnet.org/article/S0012-3692(18)31772-0/fulltext

The study will be presented in the session Lung Cancer Screening: New Questions and New Answers, Tuesday, Oct. 9, 8:45 a.m., Convention Center 207A.

Former smokers’ adherence to annual follow-up screening for lung cancer was found to be less than optimal, according to a study to be presented at the CHEST 2018 annual meeting.

Paul B. Brasher, MD, and his colleagues from the Thoracic Oncology Research Group at the Medical University of South Carolina in Charleston studied adherence to recommended low-dose computed tomography (LDCT) among Veterans Affairs patients who were at high risk for lung cancer and whose baseline LDCTs were negative.

A total of 2,106 veterans aged 55-80 years who had at least a 30-pack year smoking history were initially screened within the Veterans Health Administration Lung Cancer Screening Demonstration Project. The study tracked 1,120 of these patients for 18 months to determine their adherence to annual LDCT screening; the rate of adherence was 77.6%.

View the abstract here: https://journal.chestnet.org/article/S0012-3692(18)31772-0/fulltext

The study will be presented in the session Lung Cancer Screening: New Questions and New Answers, Tuesday, Oct. 9, 8:45 a.m., Convention Center 207A.

Former smokers’ adherence to annual follow-up screening for lung cancer was found to be less than optimal, according to a study to be presented at the CHEST 2018 annual meeting.

Paul B. Brasher, MD, and his colleagues from the Thoracic Oncology Research Group at the Medical University of South Carolina in Charleston studied adherence to recommended low-dose computed tomography (LDCT) among Veterans Affairs patients who were at high risk for lung cancer and whose baseline LDCTs were negative.

A total of 2,106 veterans aged 55-80 years who had at least a 30-pack year smoking history were initially screened within the Veterans Health Administration Lung Cancer Screening Demonstration Project. The study tracked 1,120 of these patients for 18 months to determine their adherence to annual LDCT screening; the rate of adherence was 77.6%.

View the abstract here: https://journal.chestnet.org/article/S0012-3692(18)31772-0/fulltext

The study will be presented in the session Lung Cancer Screening: New Questions and New Answers, Tuesday, Oct. 9, 8:45 a.m., Convention Center 207A.

SAN DIEGO – Don’t be satisfied with a diagnosis of angina with no obstructive coronary artery disease; push for acetylcholine testing, the findings from a trial in Scotland suggest.

M. Alexander Otto/MDedge News

Going a little further with an acetylcholine challenge in the cath lab will usually uncover microvascular or vasospastic heart problems, and this can lead to appropriate treatment. Patients will have less angina and a better quality of life at 6 months, according to investigators from the University of Glasgow (Scotland).

Invasive angiography usually ends on both sides of the Atlantic when no occlusions are found. There are concerns about the safety of going further with acetylcholine challenges, and until now, there had been no grade A evidence from a randomized trial that it improves outcomes. The Glasgow team filled the evidence gap with their presentation of the Coronary Microvascular Angina (CorMicA) trial at the Transcatheter Cardiovascular Therapeutics (TCT) annual meeting, and there wasn’t a single serious adverse event (J Am Coll Cardiol. 2018 Sep 25. doi: 10.1016/j.jacc.2018.09.006).

“This was a proof-of-concept study, which we believe [should] substantiate a large, multicenter trial,” said senior investigator Colin Berry, PhD, a professor of cardiology and imaging at the university.

Acetylcholine was infused down the pressure wire in 151 subjects diagnosed with angina with no obstructive coronary artery diseases before they left the catheter lab. Of these patients, 76 were randomized to have their results shared with their treating cardiologist, and 75 were randomized to not have their results shared. Coronary functional testing is hardly ever done, so the no-share group was considered the standard-of-care control arm. The idea was to see whether it made a difference when treating physicians knew what was causing chest pain when their patients didn’t have occlusive disease.

It turned out to make a huge difference. The diagnosis of “chest pain of noncardiac origin” almost fell off the map. Once cardiologists knew what was going on, they switched up treatment according to European Society of Cardiology guidelines for functional heart pain. Patients with microvascular angina were given beta-blockers and switched off nitrates because these drugs make angina worse in microvascular disease. Subjects with vasospasms were shifted to calcium channel blockers and long-acting nitrates and away from beta-blockers because beta-blockers make vasospasms worse.

Cardiologists who didn’t know the results kept muddling along with what patients came in on at baseline – beta-blockers in two-thirds, long-acting nitrates in half, and calcium channel blockers in a third.

Subjects who got the right treatment because of acetylcholine testing outpaced the standard care group by almost 12 points on the Seattle Angina Questionnaire at 6 months; they could walk farther and didn’t have crushing angina almost every day (P = .001). They reported a statistically significant improvement in quality of life, and they were much happier with their doctors.

“This is the first randomized, sham-controlled trial in this space”; functional testing “was routinely safe and feasible. Therapy guided by the results of physiologic testing improved outcomes” and “treatment satisfaction,” said University of Glasgow interventional cardiologist Tom Ford, MD.

Acetylcholine was infused down the pressure wire into the radial artery, with the left anterior descending coronary artery as the target vessel. A final bolus of less than 100 mcg checked for coronary artery spasms; a symptomatic constriction of greater than 90% was considered positive. Glyceryl trinitrate was used to reverse the effects.

Three-quarters of the subjects were women, which Dr. Ford noted is unusual in an angina study. The mean age was 61 years, and subjects had about a 20% chance of a heart attack within 10 years. The whole procedure, including the angiogram, randomization, and functional testing, took a median of about 60 minutes.

There were no differences in major adverse cardiac events at 6 months, at 2.6% in both groups.

One patient developed persistent atrial fibrillation with acetylcholine testing that was converted to sinus rhythm with intravenous amiodarone, without a night in the hospital.

The work was funded by the British Heart Foundation. No companies were involved. The investigators didn’t have any relevant disclosures. The TCT meeting is sponsored by the Cardiovascular Research Foundation.

aotto@mdedge.com

SOURCE: Ford TG et al. TCT 2018, Late-Breaking Trial.

SAN DIEGO – Don’t be satisfied with a diagnosis of angina with no obstructive coronary artery disease; push for acetylcholine testing, the findings from a trial in Scotland suggest.

M. Alexander Otto/MDedge News

Going a little further with an acetylcholine challenge in the cath lab will usually uncover microvascular or vasospastic heart problems, and this can lead to appropriate treatment. Patients will have less angina and a better quality of life at 6 months, according to investigators from the University of Glasgow (Scotland).

Invasive angiography usually ends on both sides of the Atlantic when no occlusions are found. There are concerns about the safety of going further with acetylcholine challenges, and until now, there had been no grade A evidence from a randomized trial that it improves outcomes. The Glasgow team filled the evidence gap with their presentation of the Coronary Microvascular Angina (CorMicA) trial at the Transcatheter Cardiovascular Therapeutics (TCT) annual meeting, and there wasn’t a single serious adverse event (J Am Coll Cardiol. 2018 Sep 25. doi: 10.1016/j.jacc.2018.09.006).

“This was a proof-of-concept study, which we believe [should] substantiate a large, multicenter trial,” said senior investigator Colin Berry, PhD, a professor of cardiology and imaging at the university.

Acetylcholine was infused down the pressure wire in 151 subjects diagnosed with angina with no obstructive coronary artery diseases before they left the catheter lab. Of these patients, 76 were randomized to have their results shared with their treating cardiologist, and 75 were randomized to not have their results shared. Coronary functional testing is hardly ever done, so the no-share group was considered the standard-of-care control arm. The idea was to see whether it made a difference when treating physicians knew what was causing chest pain when their patients didn’t have occlusive disease.

It turned out to make a huge difference. The diagnosis of “chest pain of noncardiac origin” almost fell off the map. Once cardiologists knew what was going on, they switched up treatment according to European Society of Cardiology guidelines for functional heart pain. Patients with microvascular angina were given beta-blockers and switched off nitrates because these drugs make angina worse in microvascular disease. Subjects with vasospasms were shifted to calcium channel blockers and long-acting nitrates and away from beta-blockers because beta-blockers make vasospasms worse.

Cardiologists who didn’t know the results kept muddling along with what patients came in on at baseline – beta-blockers in two-thirds, long-acting nitrates in half, and calcium channel blockers in a third.

Subjects who got the right treatment because of acetylcholine testing outpaced the standard care group by almost 12 points on the Seattle Angina Questionnaire at 6 months; they could walk farther and didn’t have crushing angina almost every day (P = .001). They reported a statistically significant improvement in quality of life, and they were much happier with their doctors.

“This is the first randomized, sham-controlled trial in this space”; functional testing “was routinely safe and feasible. Therapy guided by the results of physiologic testing improved outcomes” and “treatment satisfaction,” said University of Glasgow interventional cardiologist Tom Ford, MD.

Acetylcholine was infused down the pressure wire into the radial artery, with the left anterior descending coronary artery as the target vessel. A final bolus of less than 100 mcg checked for coronary artery spasms; a symptomatic constriction of greater than 90% was considered positive. Glyceryl trinitrate was used to reverse the effects.

Three-quarters of the subjects were women, which Dr. Ford noted is unusual in an angina study. The mean age was 61 years, and subjects had about a 20% chance of a heart attack within 10 years. The whole procedure, including the angiogram, randomization, and functional testing, took a median of about 60 minutes.

There were no differences in major adverse cardiac events at 6 months, at 2.6% in both groups.

One patient developed persistent atrial fibrillation with acetylcholine testing that was converted to sinus rhythm with intravenous amiodarone, without a night in the hospital.

The work was funded by the British Heart Foundation. No companies were involved. The investigators didn’t have any relevant disclosures. The TCT meeting is sponsored by the Cardiovascular Research Foundation.

aotto@mdedge.com

SOURCE: Ford TG et al. TCT 2018, Late-Breaking Trial.

SAN DIEGO – Don’t be satisfied with a diagnosis of angina with no obstructive coronary artery disease; push for acetylcholine testing, the findings from a trial in Scotland suggest.

M. Alexander Otto/MDedge News

Going a little further with an acetylcholine challenge in the cath lab will usually uncover microvascular or vasospastic heart problems, and this can lead to appropriate treatment. Patients will have less angina and a better quality of life at 6 months, according to investigators from the University of Glasgow (Scotland).

Invasive angiography usually ends on both sides of the Atlantic when no occlusions are found. There are concerns about the safety of going further with acetylcholine challenges, and until now, there had been no grade A evidence from a randomized trial that it improves outcomes. The Glasgow team filled the evidence gap with their presentation of the Coronary Microvascular Angina (CorMicA) trial at the Transcatheter Cardiovascular Therapeutics (TCT) annual meeting, and there wasn’t a single serious adverse event (J Am Coll Cardiol. 2018 Sep 25. doi: 10.1016/j.jacc.2018.09.006).

“This was a proof-of-concept study, which we believe [should] substantiate a large, multicenter trial,” said senior investigator Colin Berry, PhD, a professor of cardiology and imaging at the university.

Acetylcholine was infused down the pressure wire in 151 subjects diagnosed with angina with no obstructive coronary artery diseases before they left the catheter lab. Of these patients, 76 were randomized to have their results shared with their treating cardiologist, and 75 were randomized to not have their results shared. Coronary functional testing is hardly ever done, so the no-share group was considered the standard-of-care control arm. The idea was to see whether it made a difference when treating physicians knew what was causing chest pain when their patients didn’t have occlusive disease.

It turned out to make a huge difference. The diagnosis of “chest pain of noncardiac origin” almost fell off the map. Once cardiologists knew what was going on, they switched up treatment according to European Society of Cardiology guidelines for functional heart pain. Patients with microvascular angina were given beta-blockers and switched off nitrates because these drugs make angina worse in microvascular disease. Subjects with vasospasms were shifted to calcium channel blockers and long-acting nitrates and away from beta-blockers because beta-blockers make vasospasms worse.

Cardiologists who didn’t know the results kept muddling along with what patients came in on at baseline – beta-blockers in two-thirds, long-acting nitrates in half, and calcium channel blockers in a third.

Subjects who got the right treatment because of acetylcholine testing outpaced the standard care group by almost 12 points on the Seattle Angina Questionnaire at 6 months; they could walk farther and didn’t have crushing angina almost every day (P = .001). They reported a statistically significant improvement in quality of life, and they were much happier with their doctors.

“This is the first randomized, sham-controlled trial in this space”; functional testing “was routinely safe and feasible. Therapy guided by the results of physiologic testing improved outcomes” and “treatment satisfaction,” said University of Glasgow interventional cardiologist Tom Ford, MD.

Acetylcholine was infused down the pressure wire into the radial artery, with the left anterior descending coronary artery as the target vessel. A final bolus of less than 100 mcg checked for coronary artery spasms; a symptomatic constriction of greater than 90% was considered positive. Glyceryl trinitrate was used to reverse the effects.

Three-quarters of the subjects were women, which Dr. Ford noted is unusual in an angina study. The mean age was 61 years, and subjects had about a 20% chance of a heart attack within 10 years. The whole procedure, including the angiogram, randomization, and functional testing, took a median of about 60 minutes.

There were no differences in major adverse cardiac events at 6 months, at 2.6% in both groups.

One patient developed persistent atrial fibrillation with acetylcholine testing that was converted to sinus rhythm with intravenous amiodarone, without a night in the hospital.

The work was funded by the British Heart Foundation. No companies were involved. The investigators didn’t have any relevant disclosures. The TCT meeting is sponsored by the Cardiovascular Research Foundation.

aotto@mdedge.com

SOURCE: Ford TG et al. TCT 2018, Late-Breaking Trial.

Using aspirin across the board is not justified based on results of the ASPREE trial as well as on the equivocal results from other recent primary prevention trials. Also today, swings in four metabolic measures predicted death in healthy people, anticoagulation plus single antiplatelet fails noninferiority measure 1 year after stenting, and Behavioral checklist identifies children at risk of depressive and/or anxiety disorders.
Amazon Alexa
Apple Podcasts
Spotify

Using aspirin across the board is not justified based on results of the ASPREE trial as well as on the equivocal results from other recent primary prevention trials. Also today, swings in four metabolic measures predicted death in healthy people, anticoagulation plus single antiplatelet fails noninferiority measure 1 year after stenting, and Behavioral checklist identifies children at risk of depressive and/or anxiety disorders.
Amazon Alexa
Apple Podcasts
Spotify

Using aspirin across the board is not justified based on results of the ASPREE trial as well as on the equivocal results from other recent primary prevention trials. Also today, swings in four metabolic measures predicted death in healthy people, anticoagulation plus single antiplatelet fails noninferiority measure 1 year after stenting, and Behavioral checklist identifies children at risk of depressive and/or anxiety disorders.
Amazon Alexa
Apple Podcasts
Spotify

Photo courtesy of NCCN

NEW YORK—Two chimeric antigen receptor (CAR) T-cell therapies—axicabtagene ciloleucel (Yescarta ®) and tisagenlecleucel (Kymriah™)—are already approved in B-cell lymphoma by the U.S. Food and Drug Administration.

A third, lisocabtagene maraleucel, will most likely be approved before too long.

Despite differences in their costimulatory molecules, persistence, efficacy, and toxicity profiles, they all have high overall response rates and a fall-out of response during the first 3 to 6 months.

Longer-term follow-up is necessary to determine whether CAR T-cell therapy is actually curative.

“But based on the way things are looking,” said Reem Karmali, MD, of Robert H. Lurie Comprehensive Cancer Center of Northwestern University, “it seems this might be a realistic expectation.”

“CAR T-cell therapy is clearly effective and has been a ground-breaking form of therapy,” she said, “but there seems to be two sides to the coin. There are a number of challenges that we face with CAR T-cell therapy.”

Dr. Karmali outlined those challenges in a presentation at the NCCN 13^th Annual Congress: Hematologic Malignancies.

Patient selection

One of the biggest challenges, according to Dr. Karmali, is patient selection.

First, patients must have an adequate hematopoietic reserve to ensure successful CAR T-cell manufacture.

Dr. Karmali referred to the JULIET study, in which 7% of patients failed the manufacturing process due to insufficient apheresis.

Second, the patient’s disease must be stable enough to make it through the time it takes to manufacturing the CAR product, which is typically 2 to 4 weeks.

Third, the patient’s overall health must be good enough to tolerate CAR T toxicities. "The patient needs good major organ function as well as preserved neurologic function,” she explained, “to withstand the unique toxicities that come with CAR T-cell therapy, specifically CRS [cytokine release syndrome] and neurotoxicity.”

Toxicities

The major toxicities are CRS and CAR‑T‑cell‑related encephalopathy syndrome (CRES).

Dr. Karmali pointed out there is also a theoretical risk of insertional oncogenesis from viral transduction used in manufacturing the T cells, and an off-tumor on target-effect that can result in B-cell aplasia and hypogammaglobulinemia.

The profiles of inflammatory cytokines and inflammation markers differ for each CAR construct and are driven in different ways. However, IL-6 is an important mediator for CRS and IL-6 receptor blockade is effective in managing the toxicity.

The drug of choice is tocilizumab, Dr. Karmali said, and for patients who are refractory to tocilizumab, siltuximab can be used.

“Steroids are extremely useful for CRS,” she added, “because they hold down inflammation and prevent immune activation.”

Steroids are also the mainstay for managing the neurotoxicity of CAR T-cell therapy because they help stabilize the blood-brain barrier.

“It’s important to make a note,” she said, “that there actually have been a number of analyses that have looked at the impact of using IL-6 receptor blockade and steroids on CAR T-cell expansion and persistence and there really doesn’t seem to be an impact.”

“So we really ought to use these quite liberally for grade 2 or higher toxicity without worrying about dampening the effect of CAR T-cell therapy,” she emphasized.

The Lee grading criteria for the management of CRS and the CTCAE 4.03 and CARTOX-10 for CRES provide guidance in assessing and managing the toxicities.

Future directions

Dr. Karmali outlined a few new directions to address the challenges with CAR T-cell therapy, such as switchable CARs that can be turned on or off and potentially improve safety; development of new constructs that may improve homing; improvement in persistence; use of combination and sequencing strategies; and improved antigen selection that may be effective with other lymphoproliferative diseases.

“A provocative question is whether CAR T-cell therapy can actually replace autologous stem cell transplant as second-line therapy,” she said.  “This is actually being actively evaluated in a number of clinical trials including ZUMA-7 (NCT03391466).”

“I think another provocative question is whether CAR T-cell therapy can be used as consolidation in CR1 [first complete remission],” she added.

The rationale for using CAR Ts as either a replacement for autologous stem cell transplant or in CR1 is that there may be minimal residual disease present that would be enough to elicit a CAR T-cell effect, she explained.

“Ultimately, one envisions the following paradigm for the treatment of lymphomas across the board,” Dr. Karmali concluded.

“Specifically, chemotherapy with a targeted agent for rapid cytoreduction, followed by CAR T-cell consolidation in combination with either other cellular therapies or immunotherapy as a means of eradicating the minimal residual disease and ensuring a pathway to cure.” 

Photo courtesy of NCCN

NEW YORK—Two chimeric antigen receptor (CAR) T-cell therapies—axicabtagene ciloleucel (Yescarta ®) and tisagenlecleucel (Kymriah™)—are already approved in B-cell lymphoma by the U.S. Food and Drug Administration.

A third, lisocabtagene maraleucel, will most likely be approved before too long.

Despite differences in their costimulatory molecules, persistence, efficacy, and toxicity profiles, they all have high overall response rates and a fall-out of response during the first 3 to 6 months.

Longer-term follow-up is necessary to determine whether CAR T-cell therapy is actually curative.

“But based on the way things are looking,” said Reem Karmali, MD, of Robert H. Lurie Comprehensive Cancer Center of Northwestern University, “it seems this might be a realistic expectation.”

“CAR T-cell therapy is clearly effective and has been a ground-breaking form of therapy,” she said, “but there seems to be two sides to the coin. There are a number of challenges that we face with CAR T-cell therapy.”

Dr. Karmali outlined those challenges in a presentation at the NCCN 13^th Annual Congress: Hematologic Malignancies.

Patient selection

One of the biggest challenges, according to Dr. Karmali, is patient selection.

First, patients must have an adequate hematopoietic reserve to ensure successful CAR T-cell manufacture.

Dr. Karmali referred to the JULIET study, in which 7% of patients failed the manufacturing process due to insufficient apheresis.

Second, the patient’s disease must be stable enough to make it through the time it takes to manufacturing the CAR product, which is typically 2 to 4 weeks.

Third, the patient’s overall health must be good enough to tolerate CAR T toxicities. "The patient needs good major organ function as well as preserved neurologic function,” she explained, “to withstand the unique toxicities that come with CAR T-cell therapy, specifically CRS [cytokine release syndrome] and neurotoxicity.”

Toxicities

The major toxicities are CRS and CAR‑T‑cell‑related encephalopathy syndrome (CRES).

Dr. Karmali pointed out there is also a theoretical risk of insertional oncogenesis from viral transduction used in manufacturing the T cells, and an off-tumor on target-effect that can result in B-cell aplasia and hypogammaglobulinemia.

The profiles of inflammatory cytokines and inflammation markers differ for each CAR construct and are driven in different ways. However, IL-6 is an important mediator for CRS and IL-6 receptor blockade is effective in managing the toxicity.

The drug of choice is tocilizumab, Dr. Karmali said, and for patients who are refractory to tocilizumab, siltuximab can be used.

“Steroids are extremely useful for CRS,” she added, “because they hold down inflammation and prevent immune activation.”

Steroids are also the mainstay for managing the neurotoxicity of CAR T-cell therapy because they help stabilize the blood-brain barrier.

“It’s important to make a note,” she said, “that there actually have been a number of analyses that have looked at the impact of using IL-6 receptor blockade and steroids on CAR T-cell expansion and persistence and there really doesn’t seem to be an impact.”

“So we really ought to use these quite liberally for grade 2 or higher toxicity without worrying about dampening the effect of CAR T-cell therapy,” she emphasized.

The Lee grading criteria for the management of CRS and the CTCAE 4.03 and CARTOX-10 for CRES provide guidance in assessing and managing the toxicities.

Future directions

Dr. Karmali outlined a few new directions to address the challenges with CAR T-cell therapy, such as switchable CARs that can be turned on or off and potentially improve safety; development of new constructs that may improve homing; improvement in persistence; use of combination and sequencing strategies; and improved antigen selection that may be effective with other lymphoproliferative diseases.

“A provocative question is whether CAR T-cell therapy can actually replace autologous stem cell transplant as second-line therapy,” she said.  “This is actually being actively evaluated in a number of clinical trials including ZUMA-7 (NCT03391466).”

“I think another provocative question is whether CAR T-cell therapy can be used as consolidation in CR1 [first complete remission],” she added.

The rationale for using CAR Ts as either a replacement for autologous stem cell transplant or in CR1 is that there may be minimal residual disease present that would be enough to elicit a CAR T-cell effect, she explained.

“Ultimately, one envisions the following paradigm for the treatment of lymphomas across the board,” Dr. Karmali concluded.

“Specifically, chemotherapy with a targeted agent for rapid cytoreduction, followed by CAR T-cell consolidation in combination with either other cellular therapies or immunotherapy as a means of eradicating the minimal residual disease and ensuring a pathway to cure.” 

Photo courtesy of NCCN

NEW YORK—Two chimeric antigen receptor (CAR) T-cell therapies—axicabtagene ciloleucel (Yescarta ®) and tisagenlecleucel (Kymriah™)—are already approved in B-cell lymphoma by the U.S. Food and Drug Administration.

A third, lisocabtagene maraleucel, will most likely be approved before too long.

Despite differences in their costimulatory molecules, persistence, efficacy, and toxicity profiles, they all have high overall response rates and a fall-out of response during the first 3 to 6 months.

Longer-term follow-up is necessary to determine whether CAR T-cell therapy is actually curative.

“But based on the way things are looking,” said Reem Karmali, MD, of Robert H. Lurie Comprehensive Cancer Center of Northwestern University, “it seems this might be a realistic expectation.”

“CAR T-cell therapy is clearly effective and has been a ground-breaking form of therapy,” she said, “but there seems to be two sides to the coin. There are a number of challenges that we face with CAR T-cell therapy.”

Dr. Karmali outlined those challenges in a presentation at the NCCN 13^th Annual Congress: Hematologic Malignancies.

Patient selection

One of the biggest challenges, according to Dr. Karmali, is patient selection.

First, patients must have an adequate hematopoietic reserve to ensure successful CAR T-cell manufacture.

Dr. Karmali referred to the JULIET study, in which 7% of patients failed the manufacturing process due to insufficient apheresis.

Second, the patient’s disease must be stable enough to make it through the time it takes to manufacturing the CAR product, which is typically 2 to 4 weeks.

Third, the patient’s overall health must be good enough to tolerate CAR T toxicities. "The patient needs good major organ function as well as preserved neurologic function,” she explained, “to withstand the unique toxicities that come with CAR T-cell therapy, specifically CRS [cytokine release syndrome] and neurotoxicity.”

Toxicities

The major toxicities are CRS and CAR‑T‑cell‑related encephalopathy syndrome (CRES).

Dr. Karmali pointed out there is also a theoretical risk of insertional oncogenesis from viral transduction used in manufacturing the T cells, and an off-tumor on target-effect that can result in B-cell aplasia and hypogammaglobulinemia.

The profiles of inflammatory cytokines and inflammation markers differ for each CAR construct and are driven in different ways. However, IL-6 is an important mediator for CRS and IL-6 receptor blockade is effective in managing the toxicity.

The drug of choice is tocilizumab, Dr. Karmali said, and for patients who are refractory to tocilizumab, siltuximab can be used.

“Steroids are extremely useful for CRS,” she added, “because they hold down inflammation and prevent immune activation.”

Steroids are also the mainstay for managing the neurotoxicity of CAR T-cell therapy because they help stabilize the blood-brain barrier.

“It’s important to make a note,” she said, “that there actually have been a number of analyses that have looked at the impact of using IL-6 receptor blockade and steroids on CAR T-cell expansion and persistence and there really doesn’t seem to be an impact.”

“So we really ought to use these quite liberally for grade 2 or higher toxicity without worrying about dampening the effect of CAR T-cell therapy,” she emphasized.

The Lee grading criteria for the management of CRS and the CTCAE 4.03 and CARTOX-10 for CRES provide guidance in assessing and managing the toxicities.

Future directions

Dr. Karmali outlined a few new directions to address the challenges with CAR T-cell therapy, such as switchable CARs that can be turned on or off and potentially improve safety; development of new constructs that may improve homing; improvement in persistence; use of combination and sequencing strategies; and improved antigen selection that may be effective with other lymphoproliferative diseases.

“A provocative question is whether CAR T-cell therapy can actually replace autologous stem cell transplant as second-line therapy,” she said.  “This is actually being actively evaluated in a number of clinical trials including ZUMA-7 (NCT03391466).”

“I think another provocative question is whether CAR T-cell therapy can be used as consolidation in CR1 [first complete remission],” she added.

The rationale for using CAR Ts as either a replacement for autologous stem cell transplant or in CR1 is that there may be minimal residual disease present that would be enough to elicit a CAR T-cell effect, she explained.

“Ultimately, one envisions the following paradigm for the treatment of lymphomas across the board,” Dr. Karmali concluded.

“Specifically, chemotherapy with a targeted agent for rapid cytoreduction, followed by CAR T-cell consolidation in combination with either other cellular therapies or immunotherapy as a means of eradicating the minimal residual disease and ensuring a pathway to cure.”