Women and racial and ethnic minorities remain underrepresented in senior faculty roles and academic leadership positions.¹ Participation in peer review and publication in medical journals are important components of academic advancement that are emphasized in the promotion process. These efforts offer recognition of expertise and increase visibility in the scientific community, which may enhance opportunities for networking and collaboration, and provide other opportunities for career advancement. In addition, abundant evidence shows that organizations benefit from diverse teams, with better quality decisions and increased productivity resulting from diverse ideas and perspectives.²

Numerous studies have highlighted the prevalence and persistence of disparities in peer review and authorship.^3,4 Much of this work has focused on gender though gaps in these measures likely exist for racial and ethnic minorities. Yet, there are few examples of journals implementing strategies to address disparities and track results of such efforts.⁵ While institutional barriers to advancement must be addressed, we believe that medical journals have an obligation to address unequal opportunities.

At the Journal of Hospital Medicine, we are committed to leading by example and developing approaches to create equity in all facets of journal leadership and authorship.⁶ The first step towards progress is to assess the current representation of women and racial and ethnic minorities in our journal community, including first and senior authors, invited expert contributors, reviewers, and editorial team members. Like most journals, we have not collected demographic information from authors or reviewers. But now, as part of the journal’s commitment to this cause, we request that everyone in the journal community (author, reviewer, editor) update their journal account (accessible at https://mc.manuscriptcentral.com/jhm) with demographic data, including gender, race, and ethnicity.

Inclusion of these data is voluntary. While each individual will be able to access and edit their personal demographic data, the individual data will remain private and unviewable to others. As such, it will not be available for nor will it be used in the manuscript review or decision process but rather for assessing our own inclusiveness. We will review these data in aggregate to broadly inform outreach efforts to promote diversity and inclusion in our author, invited expert contributor, reviewer, and journal leadership pools. We will report on the progress of these efforts in upcoming years.

We are committed to equity in providing opportunities for academic advancement across the journal community. Diversity and inclusion are important in raising the quality of the work that we publish. Different perspectives strengthen our journal and will help us continue to advance the field of Hospital Medicine.

Disclosures

The authors have nothing to disclose.

Women and racial and ethnic minorities remain underrepresented in senior faculty roles and academic leadership positions.¹ Participation in peer review and publication in medical journals are important components of academic advancement that are emphasized in the promotion process. These efforts offer recognition of expertise and increase visibility in the scientific community, which may enhance opportunities for networking and collaboration, and provide other opportunities for career advancement. In addition, abundant evidence shows that organizations benefit from diverse teams, with better quality decisions and increased productivity resulting from diverse ideas and perspectives.²

Numerous studies have highlighted the prevalence and persistence of disparities in peer review and authorship.^3,4 Much of this work has focused on gender though gaps in these measures likely exist for racial and ethnic minorities. Yet, there are few examples of journals implementing strategies to address disparities and track results of such efforts.⁵ While institutional barriers to advancement must be addressed, we believe that medical journals have an obligation to address unequal opportunities.

At the Journal of Hospital Medicine, we are committed to leading by example and developing approaches to create equity in all facets of journal leadership and authorship.⁶ The first step towards progress is to assess the current representation of women and racial and ethnic minorities in our journal community, including first and senior authors, invited expert contributors, reviewers, and editorial team members. Like most journals, we have not collected demographic information from authors or reviewers. But now, as part of the journal’s commitment to this cause, we request that everyone in the journal community (author, reviewer, editor) update their journal account (accessible at https://mc.manuscriptcentral.com/jhm) with demographic data, including gender, race, and ethnicity.

Inclusion of these data is voluntary. While each individual will be able to access and edit their personal demographic data, the individual data will remain private and unviewable to others. As such, it will not be available for nor will it be used in the manuscript review or decision process but rather for assessing our own inclusiveness. We will review these data in aggregate to broadly inform outreach efforts to promote diversity and inclusion in our author, invited expert contributor, reviewer, and journal leadership pools. We will report on the progress of these efforts in upcoming years.

We are committed to equity in providing opportunities for academic advancement across the journal community. Diversity and inclusion are important in raising the quality of the work that we publish. Different perspectives strengthen our journal and will help us continue to advance the field of Hospital Medicine.

Disclosures

The authors have nothing to disclose.

Women and racial and ethnic minorities remain underrepresented in senior faculty roles and academic leadership positions.¹ Participation in peer review and publication in medical journals are important components of academic advancement that are emphasized in the promotion process. These efforts offer recognition of expertise and increase visibility in the scientific community, which may enhance opportunities for networking and collaboration, and provide other opportunities for career advancement. In addition, abundant evidence shows that organizations benefit from diverse teams, with better quality decisions and increased productivity resulting from diverse ideas and perspectives.²

Numerous studies have highlighted the prevalence and persistence of disparities in peer review and authorship.^3,4 Much of this work has focused on gender though gaps in these measures likely exist for racial and ethnic minorities. Yet, there are few examples of journals implementing strategies to address disparities and track results of such efforts.⁵ While institutional barriers to advancement must be addressed, we believe that medical journals have an obligation to address unequal opportunities.

At the Journal of Hospital Medicine, we are committed to leading by example and developing approaches to create equity in all facets of journal leadership and authorship.⁶ The first step towards progress is to assess the current representation of women and racial and ethnic minorities in our journal community, including first and senior authors, invited expert contributors, reviewers, and editorial team members. Like most journals, we have not collected demographic information from authors or reviewers. But now, as part of the journal’s commitment to this cause, we request that everyone in the journal community (author, reviewer, editor) update their journal account (accessible at https://mc.manuscriptcentral.com/jhm) with demographic data, including gender, race, and ethnicity.

Inclusion of these data is voluntary. While each individual will be able to access and edit their personal demographic data, the individual data will remain private and unviewable to others. As such, it will not be available for nor will it be used in the manuscript review or decision process but rather for assessing our own inclusiveness. We will review these data in aggregate to broadly inform outreach efforts to promote diversity and inclusion in our author, invited expert contributor, reviewer, and journal leadership pools. We will report on the progress of these efforts in upcoming years.

We are committed to equity in providing opportunities for academic advancement across the journal community. Diversity and inclusion are important in raising the quality of the work that we publish. Different perspectives strengthen our journal and will help us continue to advance the field of Hospital Medicine.

Disclosures

The authors have nothing to disclose.

Amsterdam – For patients with untreated mantle cell lymphoma (MCL), the anti-CD20 monoclonal antibody obinutuzumab may one day offer an alternative to rituximab, according to investigators.

Patients in the LYMA-101 trial were given four cycles of obinutuzumab in combination with dexamethasone, high-dose aracytine, and platinum chemotherapy (O-DHAP), followed by autologous stem cell transplantation (ASCT) and maintenance obinutuzumab. After a median follow-up of 14.6 months, ranging from 3.8 to 24.4 months, 85% of evaluable patients had achieved minimal residual disease (MRD) in bone marrow, reported lead author Steven Le Gouill, MD, PhD, of the University Hospital of Nantes, and his colleagues.

In this disease population, an MRD rate of 85% is “unprecedented,” Dr. Le Gouill said during his presentation at the annual congress of the European Hematology Association. Based on findings from LYMA-101 and preclinical data, Dr. Le Gouill suggested that obinutuzumab may become an alternative to rituximab, the current standard anti-CD20 antibody.

“There are few data of interest for obinutuzumab in MCL, but there is a strong rationale in the lab as obinutuzumab has a different mechanism of action against tumor cells [than rituximab], with more efficacy against MCL cells,” Dr. Le Gouill said.

Data from the ongoing phase 2 trial were drawn from 85 patients with untreated MCL who were 65 years or younger at the time of enrollment. More specifically, median patient age was 55.5 years and 17.4% of patients had blastoid disease. All patients were given the O-DHAP/ASCT/obinutuzumab protocol, with a maintenance period of 3 years. Thereafter, MRD-positive patients may receive obinutuzumab on-demand.

The primary endpoint was MRD in bone marrow after induction therapy, measured by quantitative PCR (qPCR) and droplet digital PCR (ddPCR). Secondary endpoints included response rates, survival measures, incidence of stem cell collection failure after O-DHAP, and MRD rates at additional therapeutic time points.

Owing to the ongoing nature of the study, Dr. Le Gouill focused on the primary endpoint during his presentation.

Analysis showed that 75% and 85% of evaluable patients had achieved negative MRD in bone marrow after induction, according to qPCR and ddPCR, respectively.

These early findings give “a flavor of the results in terms of efficacy,” Dr. Le Gouill said, noting that “the median follow-up is pretty short.”

Still, 1-year findings were “very promising,” he said, with a progression-free survival of 93.4% and overall survival of 96%.

Twelve patients stopped treatment before ASCT, three prior to maintenance, and nine during maintenance. Of these 24 patients, 13 stopped treatment because of adverse events. The remaining 11 patients halted therapy because of disease progression, other malignancies, or death.

From the original 85 patients, 3 patients died and 3 progressed. Considering all of these findings, and that no major toxicities were encountered, the investigators concluded that the regimen was safe.

Overall, the results suggest that further research is needed, Dr. Le Gouill concluded. “Maybe this is where obinutuzumab may have stronger efficacy in MCL, as compared to rituximab,” he said.

The study is sponsored by the Lymphoma Academic Research Organisation. The investigators reported relationships with Roche, Janssen-Cilag, Gilead, Servier, and Novartis.

SOURCE: Le Gouill S et al. EHA Congress, Abstract S103.

Amsterdam – For patients with untreated mantle cell lymphoma (MCL), the anti-CD20 monoclonal antibody obinutuzumab may one day offer an alternative to rituximab, according to investigators.

Patients in the LYMA-101 trial were given four cycles of obinutuzumab in combination with dexamethasone, high-dose aracytine, and platinum chemotherapy (O-DHAP), followed by autologous stem cell transplantation (ASCT) and maintenance obinutuzumab. After a median follow-up of 14.6 months, ranging from 3.8 to 24.4 months, 85% of evaluable patients had achieved minimal residual disease (MRD) in bone marrow, reported lead author Steven Le Gouill, MD, PhD, of the University Hospital of Nantes, and his colleagues.

In this disease population, an MRD rate of 85% is “unprecedented,” Dr. Le Gouill said during his presentation at the annual congress of the European Hematology Association. Based on findings from LYMA-101 and preclinical data, Dr. Le Gouill suggested that obinutuzumab may become an alternative to rituximab, the current standard anti-CD20 antibody.

“There are few data of interest for obinutuzumab in MCL, but there is a strong rationale in the lab as obinutuzumab has a different mechanism of action against tumor cells [than rituximab], with more efficacy against MCL cells,” Dr. Le Gouill said.

Data from the ongoing phase 2 trial were drawn from 85 patients with untreated MCL who were 65 years or younger at the time of enrollment. More specifically, median patient age was 55.5 years and 17.4% of patients had blastoid disease. All patients were given the O-DHAP/ASCT/obinutuzumab protocol, with a maintenance period of 3 years. Thereafter, MRD-positive patients may receive obinutuzumab on-demand.

The primary endpoint was MRD in bone marrow after induction therapy, measured by quantitative PCR (qPCR) and droplet digital PCR (ddPCR). Secondary endpoints included response rates, survival measures, incidence of stem cell collection failure after O-DHAP, and MRD rates at additional therapeutic time points.

Owing to the ongoing nature of the study, Dr. Le Gouill focused on the primary endpoint during his presentation.

Analysis showed that 75% and 85% of evaluable patients had achieved negative MRD in bone marrow after induction, according to qPCR and ddPCR, respectively.

These early findings give “a flavor of the results in terms of efficacy,” Dr. Le Gouill said, noting that “the median follow-up is pretty short.”

Still, 1-year findings were “very promising,” he said, with a progression-free survival of 93.4% and overall survival of 96%.

Twelve patients stopped treatment before ASCT, three prior to maintenance, and nine during maintenance. Of these 24 patients, 13 stopped treatment because of adverse events. The remaining 11 patients halted therapy because of disease progression, other malignancies, or death.

From the original 85 patients, 3 patients died and 3 progressed. Considering all of these findings, and that no major toxicities were encountered, the investigators concluded that the regimen was safe.

Overall, the results suggest that further research is needed, Dr. Le Gouill concluded. “Maybe this is where obinutuzumab may have stronger efficacy in MCL, as compared to rituximab,” he said.

The study is sponsored by the Lymphoma Academic Research Organisation. The investigators reported relationships with Roche, Janssen-Cilag, Gilead, Servier, and Novartis.

SOURCE: Le Gouill S et al. EHA Congress, Abstract S103.

Amsterdam – For patients with untreated mantle cell lymphoma (MCL), the anti-CD20 monoclonal antibody obinutuzumab may one day offer an alternative to rituximab, according to investigators.

Patients in the LYMA-101 trial were given four cycles of obinutuzumab in combination with dexamethasone, high-dose aracytine, and platinum chemotherapy (O-DHAP), followed by autologous stem cell transplantation (ASCT) and maintenance obinutuzumab. After a median follow-up of 14.6 months, ranging from 3.8 to 24.4 months, 85% of evaluable patients had achieved minimal residual disease (MRD) in bone marrow, reported lead author Steven Le Gouill, MD, PhD, of the University Hospital of Nantes, and his colleagues.

In this disease population, an MRD rate of 85% is “unprecedented,” Dr. Le Gouill said during his presentation at the annual congress of the European Hematology Association. Based on findings from LYMA-101 and preclinical data, Dr. Le Gouill suggested that obinutuzumab may become an alternative to rituximab, the current standard anti-CD20 antibody.

“There are few data of interest for obinutuzumab in MCL, but there is a strong rationale in the lab as obinutuzumab has a different mechanism of action against tumor cells [than rituximab], with more efficacy against MCL cells,” Dr. Le Gouill said.

Data from the ongoing phase 2 trial were drawn from 85 patients with untreated MCL who were 65 years or younger at the time of enrollment. More specifically, median patient age was 55.5 years and 17.4% of patients had blastoid disease. All patients were given the O-DHAP/ASCT/obinutuzumab protocol, with a maintenance period of 3 years. Thereafter, MRD-positive patients may receive obinutuzumab on-demand.

The primary endpoint was MRD in bone marrow after induction therapy, measured by quantitative PCR (qPCR) and droplet digital PCR (ddPCR). Secondary endpoints included response rates, survival measures, incidence of stem cell collection failure after O-DHAP, and MRD rates at additional therapeutic time points.

Owing to the ongoing nature of the study, Dr. Le Gouill focused on the primary endpoint during his presentation.

Analysis showed that 75% and 85% of evaluable patients had achieved negative MRD in bone marrow after induction, according to qPCR and ddPCR, respectively.

These early findings give “a flavor of the results in terms of efficacy,” Dr. Le Gouill said, noting that “the median follow-up is pretty short.”

Still, 1-year findings were “very promising,” he said, with a progression-free survival of 93.4% and overall survival of 96%.

Twelve patients stopped treatment before ASCT, three prior to maintenance, and nine during maintenance. Of these 24 patients, 13 stopped treatment because of adverse events. The remaining 11 patients halted therapy because of disease progression, other malignancies, or death.

From the original 85 patients, 3 patients died and 3 progressed. Considering all of these findings, and that no major toxicities were encountered, the investigators concluded that the regimen was safe.

Overall, the results suggest that further research is needed, Dr. Le Gouill concluded. “Maybe this is where obinutuzumab may have stronger efficacy in MCL, as compared to rituximab,” he said.

The study is sponsored by the Lymphoma Academic Research Organisation. The investigators reported relationships with Roche, Janssen-Cilag, Gilead, Servier, and Novartis.

SOURCE: Le Gouill S et al. EHA Congress, Abstract S103.

Smartphone overuse in patients with migraine is related to poor sleep quality and daytime sleepiness, resulting in diminished quality of life, a new study found. The single-center, cross-sectional comparative study used the migraine disability assessment (MIDAS) questionnaire to evaluate the disability status, and Mobile Phone Problematic Use Scale (MPPUS) was used to evaluate smartphone use frequency. The Visual Analogue Scale (VAS), 24-h Migraine Quality of Life Questionnaire (24-h MQoLQ), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to evaluate the pain intensity, quality of life, sleep quality, and daytime sleepiness. Researchers found:

• The study included 123 patients.
• There was a significant difference between the groups in terms of pain intensity, frequency, and duration.
• There was a negative correlation between MPPUS and PQSI, a strong positive correlation between MPPUS and ESS, and a negative correlation between MPPUS and 24-h MQoLQ.

Demir YP, et al. Effects of smartphone overuse on headache, sleep and quality of life in migraine patients. Neurosciences (Riyadh). 2019;24(2):115-121. doi: 10.17712/nsj.2019.2.20180037.

Smartphone overuse in patients with migraine is related to poor sleep quality and daytime sleepiness, resulting in diminished quality of life, a new study found. The single-center, cross-sectional comparative study used the migraine disability assessment (MIDAS) questionnaire to evaluate the disability status, and Mobile Phone Problematic Use Scale (MPPUS) was used to evaluate smartphone use frequency. The Visual Analogue Scale (VAS), 24-h Migraine Quality of Life Questionnaire (24-h MQoLQ), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to evaluate the pain intensity, quality of life, sleep quality, and daytime sleepiness. Researchers found:

• The study included 123 patients.
• There was a significant difference between the groups in terms of pain intensity, frequency, and duration.
• There was a negative correlation between MPPUS and PQSI, a strong positive correlation between MPPUS and ESS, and a negative correlation between MPPUS and 24-h MQoLQ.

Demir YP, et al. Effects of smartphone overuse on headache, sleep and quality of life in migraine patients. Neurosciences (Riyadh). 2019;24(2):115-121. doi: 10.17712/nsj.2019.2.20180037.

Smartphone overuse in patients with migraine is related to poor sleep quality and daytime sleepiness, resulting in diminished quality of life, a new study found. The single-center, cross-sectional comparative study used the migraine disability assessment (MIDAS) questionnaire to evaluate the disability status, and Mobile Phone Problematic Use Scale (MPPUS) was used to evaluate smartphone use frequency. The Visual Analogue Scale (VAS), 24-h Migraine Quality of Life Questionnaire (24-h MQoLQ), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to evaluate the pain intensity, quality of life, sleep quality, and daytime sleepiness. Researchers found:

• The study included 123 patients.
• There was a significant difference between the groups in terms of pain intensity, frequency, and duration.
• There was a negative correlation between MPPUS and PQSI, a strong positive correlation between MPPUS and ESS, and a negative correlation between MPPUS and 24-h MQoLQ.

Demir YP, et al. Effects of smartphone overuse on headache, sleep and quality of life in migraine patients. Neurosciences (Riyadh). 2019;24(2):115-121. doi: 10.17712/nsj.2019.2.20180037.

Vidyard Video

How strong are the links between psoriasis and psoriatic arthritis? What are the biggest challenges that keep clinicians from diagnosing PsA? And which approaches show promise in helping prevent PsA? In this expert analysis, Lihi Eder, MD, PhD, of Women’s College Research Institute, Toronto, and the University of Toronto offers answers to these questions and more.

Vidyard Video

How strong are the links between psoriasis and psoriatic arthritis? What are the biggest challenges that keep clinicians from diagnosing PsA? And which approaches show promise in helping prevent PsA? In this expert analysis, Lihi Eder, MD, PhD, of Women’s College Research Institute, Toronto, and the University of Toronto offers answers to these questions and more.

Vidyard Video

How strong are the links between psoriasis and psoriatic arthritis? What are the biggest challenges that keep clinicians from diagnosing PsA? And which approaches show promise in helping prevent PsA? In this expert analysis, Lihi Eder, MD, PhD, of Women’s College Research Institute, Toronto, and the University of Toronto offers answers to these questions and more.

FORT LAUDERDALE, FLA. – When the Food and Drug Administration in 2017 approved L-glutamine (Endari) to treat the symptoms of sickle cell disease (SCD), it was the first new drug indicated for the condition in nearly two decades. But a small study of sickle cell patients in New York has found that patients are having difficulty obtaining the drug and sticking to the regimen.

bubaone/DigitalVision Vectors

“We found out that there are multiple barriers, mostly insurance related, and that after 10 months only one-fifth of the patients were still actively taking this medication,” said Ugochi Ogu, MD, assistant director of the Sickle Cell Center for Adults at Montefiore Medical Center in New York. She presented preliminary study results at the annual meeting of the Foundation for Sickle Cell Disease Research.

L-glutamine oral powder is taken twice a day to treat the symptoms of SCD. GoodRx reports that the average cash price for a 60-day supply of L-glutamine is $2,773.

The study followed 101 patients prescribed L-glutamine at the Montefiore Medical Center. When they returned to the clinic, patients were asked about barriers to obtaining the medication and adherence to the twice-a-day dosing. The center used a nearby local specialty pharmacy to fill the prescriptions.

The study also evaluated adherence by calculating the mean possession ratio (MPR) utilizing pharmacy records. The average age of the patient population was 36 years, and 56% were women.

It’s the first study of L-glutamine barriers and adherence in SCD patients in the real-world setting, Dr. Ogu said.

At the end of the 10-month study period, 21% of the patients were actively taking the medication, she said. “Forty-three percent had discontinued the medication, and 33% never filled the prescriptions; 4% had received but never started Endari,” Dr. Ogu said.

Of the patients who never filled the prescriptions, Dr. Ogu reported that 27% said their insurer denied prior authorization, 19% said their deductible was too high, and 16% cited other insurance issues.

“So we can see that insurance alone accounted for over 60% of why patients did not receive or could not start the medication,” she said.

Most patients – 94% – either had Medicare or Medicaid; the remainder had private insurance.

Among the 43% of all study patients who stopped taking the medication, reasons given include poor adherence (47%), side effects (9%), pregnancy and breast feeding (5%), and no perceived benefit (5%), Dr. Ogu said. At the outset, pharmacy records estimated adherence at 74% by using the average MPR, a rate similar to the phase 3 trial adherence rate of 77.4%.

Patient education is important to eliminate these barriers to treatment for SCD, Dr. Ogu said. “The patients need to understand why they’re taking whatever medication you prescribe. We need to educate them about the side effects, and we need to make them understand why it’s important to take certain medications or how they’re going to help them,” she said.

But even more important, she added, is a systems-based method to deal with insurance barriers. “If 62% of the patients did not get the medication due to insurance issues, I don’t think we’re doing a good job of making it accessible to them.”

Dr. Ogu reported a financial relationship with Vertex.

SOURCE: Ogu U et al. FSCDR 2019, Abstract JSCDH-D-19-00041.




 

FORT LAUDERDALE, FLA. – When the Food and Drug Administration in 2017 approved L-glutamine (Endari) to treat the symptoms of sickle cell disease (SCD), it was the first new drug indicated for the condition in nearly two decades. But a small study of sickle cell patients in New York has found that patients are having difficulty obtaining the drug and sticking to the regimen.

bubaone/DigitalVision Vectors

“We found out that there are multiple barriers, mostly insurance related, and that after 10 months only one-fifth of the patients were still actively taking this medication,” said Ugochi Ogu, MD, assistant director of the Sickle Cell Center for Adults at Montefiore Medical Center in New York. She presented preliminary study results at the annual meeting of the Foundation for Sickle Cell Disease Research.

L-glutamine oral powder is taken twice a day to treat the symptoms of SCD. GoodRx reports that the average cash price for a 60-day supply of L-glutamine is $2,773.

The study followed 101 patients prescribed L-glutamine at the Montefiore Medical Center. When they returned to the clinic, patients were asked about barriers to obtaining the medication and adherence to the twice-a-day dosing. The center used a nearby local specialty pharmacy to fill the prescriptions.

The study also evaluated adherence by calculating the mean possession ratio (MPR) utilizing pharmacy records. The average age of the patient population was 36 years, and 56% were women.

It’s the first study of L-glutamine barriers and adherence in SCD patients in the real-world setting, Dr. Ogu said.

At the end of the 10-month study period, 21% of the patients were actively taking the medication, she said. “Forty-three percent had discontinued the medication, and 33% never filled the prescriptions; 4% had received but never started Endari,” Dr. Ogu said.

Of the patients who never filled the prescriptions, Dr. Ogu reported that 27% said their insurer denied prior authorization, 19% said their deductible was too high, and 16% cited other insurance issues.

“So we can see that insurance alone accounted for over 60% of why patients did not receive or could not start the medication,” she said.

Most patients – 94% – either had Medicare or Medicaid; the remainder had private insurance.

Among the 43% of all study patients who stopped taking the medication, reasons given include poor adherence (47%), side effects (9%), pregnancy and breast feeding (5%), and no perceived benefit (5%), Dr. Ogu said. At the outset, pharmacy records estimated adherence at 74% by using the average MPR, a rate similar to the phase 3 trial adherence rate of 77.4%.

Patient education is important to eliminate these barriers to treatment for SCD, Dr. Ogu said. “The patients need to understand why they’re taking whatever medication you prescribe. We need to educate them about the side effects, and we need to make them understand why it’s important to take certain medications or how they’re going to help them,” she said.

But even more important, she added, is a systems-based method to deal with insurance barriers. “If 62% of the patients did not get the medication due to insurance issues, I don’t think we’re doing a good job of making it accessible to them.”

Dr. Ogu reported a financial relationship with Vertex.

SOURCE: Ogu U et al. FSCDR 2019, Abstract JSCDH-D-19-00041.




 

FORT LAUDERDALE, FLA. – When the Food and Drug Administration in 2017 approved L-glutamine (Endari) to treat the symptoms of sickle cell disease (SCD), it was the first new drug indicated for the condition in nearly two decades. But a small study of sickle cell patients in New York has found that patients are having difficulty obtaining the drug and sticking to the regimen.

bubaone/DigitalVision Vectors

“We found out that there are multiple barriers, mostly insurance related, and that after 10 months only one-fifth of the patients were still actively taking this medication,” said Ugochi Ogu, MD, assistant director of the Sickle Cell Center for Adults at Montefiore Medical Center in New York. She presented preliminary study results at the annual meeting of the Foundation for Sickle Cell Disease Research.

L-glutamine oral powder is taken twice a day to treat the symptoms of SCD. GoodRx reports that the average cash price for a 60-day supply of L-glutamine is $2,773.

The study followed 101 patients prescribed L-glutamine at the Montefiore Medical Center. When they returned to the clinic, patients were asked about barriers to obtaining the medication and adherence to the twice-a-day dosing. The center used a nearby local specialty pharmacy to fill the prescriptions.

The study also evaluated adherence by calculating the mean possession ratio (MPR) utilizing pharmacy records. The average age of the patient population was 36 years, and 56% were women.

It’s the first study of L-glutamine barriers and adherence in SCD patients in the real-world setting, Dr. Ogu said.

At the end of the 10-month study period, 21% of the patients were actively taking the medication, she said. “Forty-three percent had discontinued the medication, and 33% never filled the prescriptions; 4% had received but never started Endari,” Dr. Ogu said.

Of the patients who never filled the prescriptions, Dr. Ogu reported that 27% said their insurer denied prior authorization, 19% said their deductible was too high, and 16% cited other insurance issues.

“So we can see that insurance alone accounted for over 60% of why patients did not receive or could not start the medication,” she said.

Most patients – 94% – either had Medicare or Medicaid; the remainder had private insurance.

Among the 43% of all study patients who stopped taking the medication, reasons given include poor adherence (47%), side effects (9%), pregnancy and breast feeding (5%), and no perceived benefit (5%), Dr. Ogu said. At the outset, pharmacy records estimated adherence at 74% by using the average MPR, a rate similar to the phase 3 trial adherence rate of 77.4%.

Patient education is important to eliminate these barriers to treatment for SCD, Dr. Ogu said. “The patients need to understand why they’re taking whatever medication you prescribe. We need to educate them about the side effects, and we need to make them understand why it’s important to take certain medications or how they’re going to help them,” she said.

But even more important, she added, is a systems-based method to deal with insurance barriers. “If 62% of the patients did not get the medication due to insurance issues, I don’t think we’re doing a good job of making it accessible to them.”

Dr. Ogu reported a financial relationship with Vertex.

SOURCE: Ogu U et al. FSCDR 2019, Abstract JSCDH-D-19-00041.




 

This year, progress in treating rare cancers has been named the advance of the year by the American Society of Clinical Oncology (ASCO). Advancements in treating desmoid tumors, a subtype of sarcoma, was highlighted as one of the prominent breakthroughs for a rare cancer. While sarcoma is statistically rare, the impact of the disease is great, particularly on patients and families. ASCO’s recognition of rare cancer advancements demonstrates what the sarcoma community has long known: that “rare” shouldn’t mean unimportant or overlooked. In fact, the contributions of families, patients, caregivers, clinicians, researchers, foundations, organizations, and agencies in bringing sarcoma to the forefront and giving it prominence—spending time, effort, and energy in finding effective treatments—is of utmost importance, despite the disease’s rarity.

The Sarcoma Foundation of America (SFA) is leading the race to cure sarcoma, and it is doing so through research, advocacy, and education. Since its founding in 2001, donors to the foundation have funded over $9 million in research, with almost $2 million to be invested in research projects this year alone. The SFA supports research focused on discovering and developing new and effective therapies to treat and eradicate sarcoma—often highrisk, high-reward projects that would not likely be funded by the government or commercial interests. Driving the research agenda are members of its Medical Advisory Board—some of the brightest scientific minds in the world today, several of whom also serve on the Editorial Advisory Board of this, the SFA’s official journal. We are thankful for their dedication. Together, their efforts will continue to make a difference in the lives of those impacted by sarcoma.

The Sarcoma Foundation of America
CureSarcoma.org

This year, progress in treating rare cancers has been named the advance of the year by the American Society of Clinical Oncology (ASCO). Advancements in treating desmoid tumors, a subtype of sarcoma, was highlighted as one of the prominent breakthroughs for a rare cancer. While sarcoma is statistically rare, the impact of the disease is great, particularly on patients and families. ASCO’s recognition of rare cancer advancements demonstrates what the sarcoma community has long known: that “rare” shouldn’t mean unimportant or overlooked. In fact, the contributions of families, patients, caregivers, clinicians, researchers, foundations, organizations, and agencies in bringing sarcoma to the forefront and giving it prominence—spending time, effort, and energy in finding effective treatments—is of utmost importance, despite the disease’s rarity.

The Sarcoma Foundation of America (SFA) is leading the race to cure sarcoma, and it is doing so through research, advocacy, and education. Since its founding in 2001, donors to the foundation have funded over $9 million in research, with almost $2 million to be invested in research projects this year alone. The SFA supports research focused on discovering and developing new and effective therapies to treat and eradicate sarcoma—often highrisk, high-reward projects that would not likely be funded by the government or commercial interests. Driving the research agenda are members of its Medical Advisory Board—some of the brightest scientific minds in the world today, several of whom also serve on the Editorial Advisory Board of this, the SFA’s official journal. We are thankful for their dedication. Together, their efforts will continue to make a difference in the lives of those impacted by sarcoma.

The Sarcoma Foundation of America
CureSarcoma.org

This year, progress in treating rare cancers has been named the advance of the year by the American Society of Clinical Oncology (ASCO). Advancements in treating desmoid tumors, a subtype of sarcoma, was highlighted as one of the prominent breakthroughs for a rare cancer. While sarcoma is statistically rare, the impact of the disease is great, particularly on patients and families. ASCO’s recognition of rare cancer advancements demonstrates what the sarcoma community has long known: that “rare” shouldn’t mean unimportant or overlooked. In fact, the contributions of families, patients, caregivers, clinicians, researchers, foundations, organizations, and agencies in bringing sarcoma to the forefront and giving it prominence—spending time, effort, and energy in finding effective treatments—is of utmost importance, despite the disease’s rarity.

The Sarcoma Foundation of America (SFA) is leading the race to cure sarcoma, and it is doing so through research, advocacy, and education. Since its founding in 2001, donors to the foundation have funded over $9 million in research, with almost $2 million to be invested in research projects this year alone. The SFA supports research focused on discovering and developing new and effective therapies to treat and eradicate sarcoma—often highrisk, high-reward projects that would not likely be funded by the government or commercial interests. Driving the research agenda are members of its Medical Advisory Board—some of the brightest scientific minds in the world today, several of whom also serve on the Editorial Advisory Board of this, the SFA’s official journal. We are thankful for their dedication. Together, their efforts will continue to make a difference in the lives of those impacted by sarcoma.

The Sarcoma Foundation of America
CureSarcoma.org

More Americans are meeting federal physical activity guidelines, but there is a considerable difference in exercise prevalence between urban and rural populations, according to the Centers for Disease Control and Prevention.

The prevalence of meeting the aerobic and muscle-strengthening recommendations in the 2008 Physical Activity Guidelines for Americans rose from 18.2% of adults in 2008 to 24.3% in 2017, but despite that increase, “insufficient participation in physical activity remains a public health concern,” Geoffrey P. Whitfield, PhD, and his associates said in the Morbidity and Mortality Weekly Report.

There was progress among both urban and rural residents, but those in rural areas were behind at the start of the study period in 2008 and remained behind in 2017. The prevalence of meeting the activity guideline started at 13.3% for rural residents and 19.4% for urbanites and rose to 19.6% and 25.3%, respectively, in 2017 – that’s an annual percentage point change of 0.5% for each population, the investigators reported. Rates among women were well below those of men in both populations.

Rural communities may lack the infrastructure, such as sidewalks, schoolyards, and parks, to support physical activities, or rural residents may get more exercise through occupational and domestic tasks, rather than through the leisure-time activities that are the focus of the National Health Interview Survey, which was the source of the study data, Dr. Whitfield and his associates suggested.

The 2008 federal guidelines recommend that adults get 150-300 minutes of moderate-intensity or 75-150 minutes of vigorous-intensity aerobic physical activity per week, along with muscle-strengthening activities of at least moderate intensity involving all major muscle groups on 2 or more days each week.

rfranki@mdedge.com

SOURCE: Whitfield GP et al. MMWR. 2019 Jun 14;68(23):514-8.

More Americans are meeting federal physical activity guidelines, but there is a considerable difference in exercise prevalence between urban and rural populations, according to the Centers for Disease Control and Prevention.

The prevalence of meeting the aerobic and muscle-strengthening recommendations in the 2008 Physical Activity Guidelines for Americans rose from 18.2% of adults in 2008 to 24.3% in 2017, but despite that increase, “insufficient participation in physical activity remains a public health concern,” Geoffrey P. Whitfield, PhD, and his associates said in the Morbidity and Mortality Weekly Report.

There was progress among both urban and rural residents, but those in rural areas were behind at the start of the study period in 2008 and remained behind in 2017. The prevalence of meeting the activity guideline started at 13.3% for rural residents and 19.4% for urbanites and rose to 19.6% and 25.3%, respectively, in 2017 – that’s an annual percentage point change of 0.5% for each population, the investigators reported. Rates among women were well below those of men in both populations.

Rural communities may lack the infrastructure, such as sidewalks, schoolyards, and parks, to support physical activities, or rural residents may get more exercise through occupational and domestic tasks, rather than through the leisure-time activities that are the focus of the National Health Interview Survey, which was the source of the study data, Dr. Whitfield and his associates suggested.

The 2008 federal guidelines recommend that adults get 150-300 minutes of moderate-intensity or 75-150 minutes of vigorous-intensity aerobic physical activity per week, along with muscle-strengthening activities of at least moderate intensity involving all major muscle groups on 2 or more days each week.

rfranki@mdedge.com

SOURCE: Whitfield GP et al. MMWR. 2019 Jun 14;68(23):514-8.

More Americans are meeting federal physical activity guidelines, but there is a considerable difference in exercise prevalence between urban and rural populations, according to the Centers for Disease Control and Prevention.

The prevalence of meeting the aerobic and muscle-strengthening recommendations in the 2008 Physical Activity Guidelines for Americans rose from 18.2% of adults in 2008 to 24.3% in 2017, but despite that increase, “insufficient participation in physical activity remains a public health concern,” Geoffrey P. Whitfield, PhD, and his associates said in the Morbidity and Mortality Weekly Report.

There was progress among both urban and rural residents, but those in rural areas were behind at the start of the study period in 2008 and remained behind in 2017. The prevalence of meeting the activity guideline started at 13.3% for rural residents and 19.4% for urbanites and rose to 19.6% and 25.3%, respectively, in 2017 – that’s an annual percentage point change of 0.5% for each population, the investigators reported. Rates among women were well below those of men in both populations.

Rural communities may lack the infrastructure, such as sidewalks, schoolyards, and parks, to support physical activities, or rural residents may get more exercise through occupational and domestic tasks, rather than through the leisure-time activities that are the focus of the National Health Interview Survey, which was the source of the study data, Dr. Whitfield and his associates suggested.

The 2008 federal guidelines recommend that adults get 150-300 minutes of moderate-intensity or 75-150 minutes of vigorous-intensity aerobic physical activity per week, along with muscle-strengthening activities of at least moderate intensity involving all major muscle groups on 2 or more days each week.

rfranki@mdedge.com

SOURCE: Whitfield GP et al. MMWR. 2019 Jun 14;68(23):514-8.

CHICAGO – A six-drug combination produced complete responses in previously untreated, high-risk diffuse large B-cell lymphoma (DLBCL) patients in a phase 2 trial.

Jennifer Smith/ MDedge News

Induction with durvalumab and R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) produced complete response rates of 54% in the entire cohort and 41% in patients with double- or triple-hit lymphoma. Immune-related adverse events (AEs) were common with this regimen, but no unexpected AEs occurred, according to researchers.

Grzegorz S. Nowakowski, MD, of the Mayo Clinic in Rochester, Minn., and colleagues presented these results in a poster at the annual meeting of the American Society of Clinical Oncology.

Treatment

The phase 2 trial (NCT03003520) was designed to assess durvalumab plus R-CHOP as well as durvalumab plus R-CHOP and lenalidomide (R2-CHOP) in patients with previously untreated, high-risk DLBCL. However, the R2-CHOP arm was closed early.

In cycle one, all patients received durvalumab plus R-CHOP. For subsequent cycles, patients with activated B-cell (ABC) DLBCL were assigned to durvalumab plus R2-CHOP, while patients with non-ABC DLBCL continued on durvalumab plus R-CHOP.

The R2-CHOP arm was closed early due to safety issues observed in trials combining checkpoint inhibitors with immunomodulatory agents. A partial clinical hold was placed on the R2-CHOP arm, but patients could continue on the regimen if they experienced a clinical benefit. Any patients with ABC DLBCL who were enrolled after the partial hold received treatment with durvalumab plus R-CHOP.

Induction was given for up to eight cycles and was followed by consolidation with durvalumab alone for up to 12 months from the start of induction.

Patient characteristics

The researchers presented data on 43 patients in the durvalumab plus R-CHOP arm. The patients’ median age was 62 years, and 61% were men.

“I think it’s worth noting that 46% of patients in the durvalumab plus R-CHOP group had very high-risk features, including double-hit or triple-hit genetic features,” said Justin Kline, MD, of the University of Chicago Medicine who reviewed this study in a poster discussion session.

Specifically, 30% of patients had double-hit lymphoma, and 16% had triple-hit lymphoma. Most patients had a high-intermediate-risk (49%) or high-risk (21%) International Prognostic Index score, and 79% of patients had Ann Arbor stage IV disease.

Efficacy

As of Aug. 2, 2018, 70% of patients had completed induction, 2% had completed consolidation, 44% remained on treatment, and 54% had discontinued therapy. The most common reasons for stopping treatment were progression (16%), AEs (14%), and consent withdrawal (12%).

“The combination of durvalumab plus R-CHOP demonstrated encouraging response rates … in subjects with high-risk DLBCL, including double- and triple-hit lymphomas,” Dr. Kline said.

The complete response rate was 54% (20/37) at the end of induction and 68% (n = 25) at the end of consolidation. The partial response rate at the end of consolidation was 30% (n = 11).

In patients with double- or triple-hit lymphoma, the complete response rate at the end of induction was 41% (7/17). The overall response rate in this group was 88% (n = 15).

Safety

“The safety profile was as expected for the components of the combination, and no new safety signals were observed,” Dr. Kline said.

He noted that AEs of special interest, or immune-related AEs, occurred in 61% of patients, but most of these events were grade 1 or 2.

AEs of special interest included diarrhea (28%), rash (23%), infusion-related reactions (16%), dermatitis (12%), hypothyroidism (5%), myocarditis (5%), adrenal insufficiency (2%), and hepatitis (2%).

Grade 3 or 4 AEs of special interest included infusion-related reactions (5%), rash (2%), diarrhea (2%), and hepatitis (2%).

The safety and efficacy results support further evaluation of durvalumab plus R-CHOP, although it will be important to identify DLBCL patients who are more likely to derive a clinical benefit from PD-1 or PD-L1 blockade, Dr. Kline said.

“This early study showed that the combination is feasible,” Dr. Nowakowski added. “I think, down the road, we’ll need to identify patients who can actually benefit from this combination. We definitely have clinical evidence of exceptional responses to PD-1 blockade.”

The trial was sponsored by Celgene. Dr. Nowakowski reported relationships with Celgene, Genentech, MorphoSys, and NanoString Technologies. Dr. Kline reported relationships with Cardinal Health, Merck, Seattle Genetics, Kite/Gilead, ITeos Therapeutics, and Bristol-Myers Squibb.

jensmith@mdedge.com

SOURCE: Nowakowski GS et al. ASCO 2019, Abstract 7520.

CHICAGO – A six-drug combination produced complete responses in previously untreated, high-risk diffuse large B-cell lymphoma (DLBCL) patients in a phase 2 trial.

Jennifer Smith/ MDedge News

Induction with durvalumab and R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) produced complete response rates of 54% in the entire cohort and 41% in patients with double- or triple-hit lymphoma. Immune-related adverse events (AEs) were common with this regimen, but no unexpected AEs occurred, according to researchers.

Grzegorz S. Nowakowski, MD, of the Mayo Clinic in Rochester, Minn., and colleagues presented these results in a poster at the annual meeting of the American Society of Clinical Oncology.

Treatment

The phase 2 trial (NCT03003520) was designed to assess durvalumab plus R-CHOP as well as durvalumab plus R-CHOP and lenalidomide (R2-CHOP) in patients with previously untreated, high-risk DLBCL. However, the R2-CHOP arm was closed early.

In cycle one, all patients received durvalumab plus R-CHOP. For subsequent cycles, patients with activated B-cell (ABC) DLBCL were assigned to durvalumab plus R2-CHOP, while patients with non-ABC DLBCL continued on durvalumab plus R-CHOP.

The R2-CHOP arm was closed early due to safety issues observed in trials combining checkpoint inhibitors with immunomodulatory agents. A partial clinical hold was placed on the R2-CHOP arm, but patients could continue on the regimen if they experienced a clinical benefit. Any patients with ABC DLBCL who were enrolled after the partial hold received treatment with durvalumab plus R-CHOP.

Induction was given for up to eight cycles and was followed by consolidation with durvalumab alone for up to 12 months from the start of induction.

Patient characteristics

The researchers presented data on 43 patients in the durvalumab plus R-CHOP arm. The patients’ median age was 62 years, and 61% were men.

“I think it’s worth noting that 46% of patients in the durvalumab plus R-CHOP group had very high-risk features, including double-hit or triple-hit genetic features,” said Justin Kline, MD, of the University of Chicago Medicine who reviewed this study in a poster discussion session.

Specifically, 30% of patients had double-hit lymphoma, and 16% had triple-hit lymphoma. Most patients had a high-intermediate-risk (49%) or high-risk (21%) International Prognostic Index score, and 79% of patients had Ann Arbor stage IV disease.

Efficacy

As of Aug. 2, 2018, 70% of patients had completed induction, 2% had completed consolidation, 44% remained on treatment, and 54% had discontinued therapy. The most common reasons for stopping treatment were progression (16%), AEs (14%), and consent withdrawal (12%).

“The combination of durvalumab plus R-CHOP demonstrated encouraging response rates … in subjects with high-risk DLBCL, including double- and triple-hit lymphomas,” Dr. Kline said.

The complete response rate was 54% (20/37) at the end of induction and 68% (n = 25) at the end of consolidation. The partial response rate at the end of consolidation was 30% (n = 11).

In patients with double- or triple-hit lymphoma, the complete response rate at the end of induction was 41% (7/17). The overall response rate in this group was 88% (n = 15).

Safety

“The safety profile was as expected for the components of the combination, and no new safety signals were observed,” Dr. Kline said.

He noted that AEs of special interest, or immune-related AEs, occurred in 61% of patients, but most of these events were grade 1 or 2.

AEs of special interest included diarrhea (28%), rash (23%), infusion-related reactions (16%), dermatitis (12%), hypothyroidism (5%), myocarditis (5%), adrenal insufficiency (2%), and hepatitis (2%).

Grade 3 or 4 AEs of special interest included infusion-related reactions (5%), rash (2%), diarrhea (2%), and hepatitis (2%).

The safety and efficacy results support further evaluation of durvalumab plus R-CHOP, although it will be important to identify DLBCL patients who are more likely to derive a clinical benefit from PD-1 or PD-L1 blockade, Dr. Kline said.

“This early study showed that the combination is feasible,” Dr. Nowakowski added. “I think, down the road, we’ll need to identify patients who can actually benefit from this combination. We definitely have clinical evidence of exceptional responses to PD-1 blockade.”

The trial was sponsored by Celgene. Dr. Nowakowski reported relationships with Celgene, Genentech, MorphoSys, and NanoString Technologies. Dr. Kline reported relationships with Cardinal Health, Merck, Seattle Genetics, Kite/Gilead, ITeos Therapeutics, and Bristol-Myers Squibb.

jensmith@mdedge.com

SOURCE: Nowakowski GS et al. ASCO 2019, Abstract 7520.

CHICAGO – A six-drug combination produced complete responses in previously untreated, high-risk diffuse large B-cell lymphoma (DLBCL) patients in a phase 2 trial.

Jennifer Smith/ MDedge News

Induction with durvalumab and R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) produced complete response rates of 54% in the entire cohort and 41% in patients with double- or triple-hit lymphoma. Immune-related adverse events (AEs) were common with this regimen, but no unexpected AEs occurred, according to researchers.

Grzegorz S. Nowakowski, MD, of the Mayo Clinic in Rochester, Minn., and colleagues presented these results in a poster at the annual meeting of the American Society of Clinical Oncology.

Treatment

The phase 2 trial (NCT03003520) was designed to assess durvalumab plus R-CHOP as well as durvalumab plus R-CHOP and lenalidomide (R2-CHOP) in patients with previously untreated, high-risk DLBCL. However, the R2-CHOP arm was closed early.

In cycle one, all patients received durvalumab plus R-CHOP. For subsequent cycles, patients with activated B-cell (ABC) DLBCL were assigned to durvalumab plus R2-CHOP, while patients with non-ABC DLBCL continued on durvalumab plus R-CHOP.

The R2-CHOP arm was closed early due to safety issues observed in trials combining checkpoint inhibitors with immunomodulatory agents. A partial clinical hold was placed on the R2-CHOP arm, but patients could continue on the regimen if they experienced a clinical benefit. Any patients with ABC DLBCL who were enrolled after the partial hold received treatment with durvalumab plus R-CHOP.

Induction was given for up to eight cycles and was followed by consolidation with durvalumab alone for up to 12 months from the start of induction.

Patient characteristics

The researchers presented data on 43 patients in the durvalumab plus R-CHOP arm. The patients’ median age was 62 years, and 61% were men.

“I think it’s worth noting that 46% of patients in the durvalumab plus R-CHOP group had very high-risk features, including double-hit or triple-hit genetic features,” said Justin Kline, MD, of the University of Chicago Medicine who reviewed this study in a poster discussion session.

Specifically, 30% of patients had double-hit lymphoma, and 16% had triple-hit lymphoma. Most patients had a high-intermediate-risk (49%) or high-risk (21%) International Prognostic Index score, and 79% of patients had Ann Arbor stage IV disease.

Efficacy

As of Aug. 2, 2018, 70% of patients had completed induction, 2% had completed consolidation, 44% remained on treatment, and 54% had discontinued therapy. The most common reasons for stopping treatment were progression (16%), AEs (14%), and consent withdrawal (12%).

“The combination of durvalumab plus R-CHOP demonstrated encouraging response rates … in subjects with high-risk DLBCL, including double- and triple-hit lymphomas,” Dr. Kline said.

The complete response rate was 54% (20/37) at the end of induction and 68% (n = 25) at the end of consolidation. The partial response rate at the end of consolidation was 30% (n = 11).

In patients with double- or triple-hit lymphoma, the complete response rate at the end of induction was 41% (7/17). The overall response rate in this group was 88% (n = 15).

Safety

“The safety profile was as expected for the components of the combination, and no new safety signals were observed,” Dr. Kline said.

He noted that AEs of special interest, or immune-related AEs, occurred in 61% of patients, but most of these events were grade 1 or 2.

AEs of special interest included diarrhea (28%), rash (23%), infusion-related reactions (16%), dermatitis (12%), hypothyroidism (5%), myocarditis (5%), adrenal insufficiency (2%), and hepatitis (2%).

Grade 3 or 4 AEs of special interest included infusion-related reactions (5%), rash (2%), diarrhea (2%), and hepatitis (2%).

The safety and efficacy results support further evaluation of durvalumab plus R-CHOP, although it will be important to identify DLBCL patients who are more likely to derive a clinical benefit from PD-1 or PD-L1 blockade, Dr. Kline said.

“This early study showed that the combination is feasible,” Dr. Nowakowski added. “I think, down the road, we’ll need to identify patients who can actually benefit from this combination. We definitely have clinical evidence of exceptional responses to PD-1 blockade.”

The trial was sponsored by Celgene. Dr. Nowakowski reported relationships with Celgene, Genentech, MorphoSys, and NanoString Technologies. Dr. Kline reported relationships with Cardinal Health, Merck, Seattle Genetics, Kite/Gilead, ITeos Therapeutics, and Bristol-Myers Squibb.

jensmith@mdedge.com

SOURCE: Nowakowski GS et al. ASCO 2019, Abstract 7520.

Poor subjective sleep quality was associated with subsequent symptomatic exacerbations of chronic obstructive pulmonary disease in an 18-month prospective study of 480 patients.

©marcociannarel/Thinkstock

“Poor sleep quality in COPD has previously been associated with reduced health-related quality of life and reduced physical activity during the day,” wrote Matthew Shorofsky, MD, of McGill University, Montreal, and associates. Their report is in CHEST. “However, to our knowledge, this is the first population-based longitudinal study evaluating exacerbation risk in relation to subjective sleep disturbances and assessing previously diagnosed and undiagnosed COPD.”

The study included participants enrolled in the Canadian Respiratory Research Network and the Canadian Cohort Obstructive Lung Disease (CanCOLD) study who had COPD, available baseline PSQI scores, and 18 months of follow-up data. The PSQI includes 19 questions on sleep quality, latency, duration, efficiency, disturbances, use of sleep medications, and daytime dysfunction. Total score ranges between 0 and 21, and a score above 5 is considered poor sleep. Online patient surveys and quarterly phone interviews were used to track symptom-based exacerbations (at least 48 hours of increased dyspnea, sputum volume, or sputum purulence) and event-based exacerbations (a symptom-based exacerbation plus the use antibiotics or corticosteroids or health services).

At baseline, 203 patients met the PSQI threshold for poor sleep quality. During follow-up, 185 patients had at least one COPD exacerbation. Poor sleep at baseline was significantly more prevalent among patients with symptoms-based COPD exacerbations (50.3%) than among patients without symptoms-based exacerbations (37.3%; P = .01). Poor baseline sleep quality remained a significant risk factor for symptom-based exacerbations of COPD even after the researchers accounted for the effect of age, gender, body mass index, smoking, depression, angina, baseline inhaled respiratory medications, forced expiratory volume in 1 second %predicted, and modified Medical Research Council (mMRC) dyspnea scale (adjusted risk ratio, 1.09; 95% confidence interval, 1.01-1.18; P =.02).

Patients with at least one symptomatic exacerbation of COPD were significantly more likely to meet the threshold for poor sleep quality on the Pittsburgh Sleep Quality Index and have significantly higher median PSQI scores compared with patients without exacerbations (6.0 [interquartile range, 3.0 to 8.0] vs. 5.0 [2.0 to 7.0]; P = .01). Poor baseline sleep quality also was associated with event-based exacerbations and with a shorter time to symptoms-based exacerbations. Sleep disturbances, such as rising to void or experiencing respiratory issues or pain during sleep, correlated most strongly with symptoms-based exacerbations.

Several factors could explain the link between poor sleep quality and COPD exacerbations, the investigators wrote. Patients with inadequately controlled COPD have more frequent and unstable respiratory symptoms, which could disrupt sleep either directly or indirectly (secondary to medication use or anxiety, for example). Conversely, sleep disruption can impede immune function and increase systemic inflammation, which might worsen COPD control and increase exacerbation risk. Poor sleep can impair memory and cognition, “potentially fostering medication nonadherence and symptom flare-up, especially in the older COPD population.” Although the link is poorly understood, patients with COPD often have comorbid obstructive sleep apnea (OSA), which is associated with COPD exacerbations, the researchers wrote. Treating OSA is associated with improved COPD morbidity and fewer exacerbations and hospitalizations.

The researchers acknowledged limitations to their study design. “Individuals with asthma or other obstructive lung diseases could not be definitively excluded; methacholine challenges were not performed. However, analyses excluding self-reported asthma were consistent with our main results. Second, because definitions of COPD exacerbation vary among studies, comparison may be limited, but CanCOLD used a standard definition, as recommended by GOLD.”

The CanCOLD study has received funding from the Canadian Respiratory Research Network, Astra Zeneca Canada, Boehringer Ingelheim Canada, GlaxoSmithKline Canada, Novartis, Merck Nycomed, Pfizer Canada, and Theratechnologies. Dr. Shorofsky had no disclosures. Several coinvestigators reported ties to GlaxoSmithKline, Novartis, Boehringer Ingelheim, Merck, Almirall, and Theratechnologies.

SOURCE: Shorofsky M et al. CHEST. 2019 May 28. doi: 10.1016/j.chest.2019.04.132.

Poor subjective sleep quality was associated with subsequent symptomatic exacerbations of chronic obstructive pulmonary disease in an 18-month prospective study of 480 patients.

©marcociannarel/Thinkstock

“Poor sleep quality in COPD has previously been associated with reduced health-related quality of life and reduced physical activity during the day,” wrote Matthew Shorofsky, MD, of McGill University, Montreal, and associates. Their report is in CHEST. “However, to our knowledge, this is the first population-based longitudinal study evaluating exacerbation risk in relation to subjective sleep disturbances and assessing previously diagnosed and undiagnosed COPD.”

The study included participants enrolled in the Canadian Respiratory Research Network and the Canadian Cohort Obstructive Lung Disease (CanCOLD) study who had COPD, available baseline PSQI scores, and 18 months of follow-up data. The PSQI includes 19 questions on sleep quality, latency, duration, efficiency, disturbances, use of sleep medications, and daytime dysfunction. Total score ranges between 0 and 21, and a score above 5 is considered poor sleep. Online patient surveys and quarterly phone interviews were used to track symptom-based exacerbations (at least 48 hours of increased dyspnea, sputum volume, or sputum purulence) and event-based exacerbations (a symptom-based exacerbation plus the use antibiotics or corticosteroids or health services).

At baseline, 203 patients met the PSQI threshold for poor sleep quality. During follow-up, 185 patients had at least one COPD exacerbation. Poor sleep at baseline was significantly more prevalent among patients with symptoms-based COPD exacerbations (50.3%) than among patients without symptoms-based exacerbations (37.3%; P = .01). Poor baseline sleep quality remained a significant risk factor for symptom-based exacerbations of COPD even after the researchers accounted for the effect of age, gender, body mass index, smoking, depression, angina, baseline inhaled respiratory medications, forced expiratory volume in 1 second %predicted, and modified Medical Research Council (mMRC) dyspnea scale (adjusted risk ratio, 1.09; 95% confidence interval, 1.01-1.18; P =.02).

Patients with at least one symptomatic exacerbation of COPD were significantly more likely to meet the threshold for poor sleep quality on the Pittsburgh Sleep Quality Index and have significantly higher median PSQI scores compared with patients without exacerbations (6.0 [interquartile range, 3.0 to 8.0] vs. 5.0 [2.0 to 7.0]; P = .01). Poor baseline sleep quality also was associated with event-based exacerbations and with a shorter time to symptoms-based exacerbations. Sleep disturbances, such as rising to void or experiencing respiratory issues or pain during sleep, correlated most strongly with symptoms-based exacerbations.

Several factors could explain the link between poor sleep quality and COPD exacerbations, the investigators wrote. Patients with inadequately controlled COPD have more frequent and unstable respiratory symptoms, which could disrupt sleep either directly or indirectly (secondary to medication use or anxiety, for example). Conversely, sleep disruption can impede immune function and increase systemic inflammation, which might worsen COPD control and increase exacerbation risk. Poor sleep can impair memory and cognition, “potentially fostering medication nonadherence and symptom flare-up, especially in the older COPD population.” Although the link is poorly understood, patients with COPD often have comorbid obstructive sleep apnea (OSA), which is associated with COPD exacerbations, the researchers wrote. Treating OSA is associated with improved COPD morbidity and fewer exacerbations and hospitalizations.

The researchers acknowledged limitations to their study design. “Individuals with asthma or other obstructive lung diseases could not be definitively excluded; methacholine challenges were not performed. However, analyses excluding self-reported asthma were consistent with our main results. Second, because definitions of COPD exacerbation vary among studies, comparison may be limited, but CanCOLD used a standard definition, as recommended by GOLD.”

The CanCOLD study has received funding from the Canadian Respiratory Research Network, Astra Zeneca Canada, Boehringer Ingelheim Canada, GlaxoSmithKline Canada, Novartis, Merck Nycomed, Pfizer Canada, and Theratechnologies. Dr. Shorofsky had no disclosures. Several coinvestigators reported ties to GlaxoSmithKline, Novartis, Boehringer Ingelheim, Merck, Almirall, and Theratechnologies.

SOURCE: Shorofsky M et al. CHEST. 2019 May 28. doi: 10.1016/j.chest.2019.04.132.

Poor subjective sleep quality was associated with subsequent symptomatic exacerbations of chronic obstructive pulmonary disease in an 18-month prospective study of 480 patients.

©marcociannarel/Thinkstock

“Poor sleep quality in COPD has previously been associated with reduced health-related quality of life and reduced physical activity during the day,” wrote Matthew Shorofsky, MD, of McGill University, Montreal, and associates. Their report is in CHEST. “However, to our knowledge, this is the first population-based longitudinal study evaluating exacerbation risk in relation to subjective sleep disturbances and assessing previously diagnosed and undiagnosed COPD.”

The study included participants enrolled in the Canadian Respiratory Research Network and the Canadian Cohort Obstructive Lung Disease (CanCOLD) study who had COPD, available baseline PSQI scores, and 18 months of follow-up data. The PSQI includes 19 questions on sleep quality, latency, duration, efficiency, disturbances, use of sleep medications, and daytime dysfunction. Total score ranges between 0 and 21, and a score above 5 is considered poor sleep. Online patient surveys and quarterly phone interviews were used to track symptom-based exacerbations (at least 48 hours of increased dyspnea, sputum volume, or sputum purulence) and event-based exacerbations (a symptom-based exacerbation plus the use antibiotics or corticosteroids or health services).

At baseline, 203 patients met the PSQI threshold for poor sleep quality. During follow-up, 185 patients had at least one COPD exacerbation. Poor sleep at baseline was significantly more prevalent among patients with symptoms-based COPD exacerbations (50.3%) than among patients without symptoms-based exacerbations (37.3%; P = .01). Poor baseline sleep quality remained a significant risk factor for symptom-based exacerbations of COPD even after the researchers accounted for the effect of age, gender, body mass index, smoking, depression, angina, baseline inhaled respiratory medications, forced expiratory volume in 1 second %predicted, and modified Medical Research Council (mMRC) dyspnea scale (adjusted risk ratio, 1.09; 95% confidence interval, 1.01-1.18; P =.02).

Patients with at least one symptomatic exacerbation of COPD were significantly more likely to meet the threshold for poor sleep quality on the Pittsburgh Sleep Quality Index and have significantly higher median PSQI scores compared with patients without exacerbations (6.0 [interquartile range, 3.0 to 8.0] vs. 5.0 [2.0 to 7.0]; P = .01). Poor baseline sleep quality also was associated with event-based exacerbations and with a shorter time to symptoms-based exacerbations. Sleep disturbances, such as rising to void or experiencing respiratory issues or pain during sleep, correlated most strongly with symptoms-based exacerbations.

Several factors could explain the link between poor sleep quality and COPD exacerbations, the investigators wrote. Patients with inadequately controlled COPD have more frequent and unstable respiratory symptoms, which could disrupt sleep either directly or indirectly (secondary to medication use or anxiety, for example). Conversely, sleep disruption can impede immune function and increase systemic inflammation, which might worsen COPD control and increase exacerbation risk. Poor sleep can impair memory and cognition, “potentially fostering medication nonadherence and symptom flare-up, especially in the older COPD population.” Although the link is poorly understood, patients with COPD often have comorbid obstructive sleep apnea (OSA), which is associated with COPD exacerbations, the researchers wrote. Treating OSA is associated with improved COPD morbidity and fewer exacerbations and hospitalizations.

The researchers acknowledged limitations to their study design. “Individuals with asthma or other obstructive lung diseases could not be definitively excluded; methacholine challenges were not performed. However, analyses excluding self-reported asthma were consistent with our main results. Second, because definitions of COPD exacerbation vary among studies, comparison may be limited, but CanCOLD used a standard definition, as recommended by GOLD.”

The CanCOLD study has received funding from the Canadian Respiratory Research Network, Astra Zeneca Canada, Boehringer Ingelheim Canada, GlaxoSmithKline Canada, Novartis, Merck Nycomed, Pfizer Canada, and Theratechnologies. Dr. Shorofsky had no disclosures. Several coinvestigators reported ties to GlaxoSmithKline, Novartis, Boehringer Ingelheim, Merck, Almirall, and Theratechnologies.

SOURCE: Shorofsky M et al. CHEST. 2019 May 28. doi: 10.1016/j.chest.2019.04.132.

The strategy of simultaneously exploiting deficient DNA damage repair and unleashing the immune response could expand treatment options for hard-to-treat breast and ovarian cancers, findings of the TOPACIO/KEYNOTE-162 trial suggest.

Triple-negative breast cancer (TNBC) and high-grade serous ovarian carcinoma share a number of genomic features, including a high frequency of BRCA1 and BRCA2 inactivation (Nature. 2012;490:61-70), as well as potential immunoreactivity (Lancet Oncol. 2018;19:40-50).

The open-label, single-arm phase 1/2 trial therefore tested the combination of niraparib (Zejula), an oral poly (ADP-ribose) polymerase (PARP) inhibitor, and pembrolizumab (Keytruda), an antibody to programmed death 1 (PD-1), among more than 100 patients with advanced or metastatic TNBC or recurrent platinum-resistant ovarian carcinoma. Patients were enrolled irrespective of BRCA mutation status or programmed death-ligand 1 (PD-L1) expression.

Main results, reported in JAMA Oncology, showed that the combination was safe, and about a fifth of patients with each type of cancer had an objective response. Median progression-free survival (PFS) was about 2 months in those with TNBC overall (although it exceeded 8 months in the subset with a tumor BRCA mutation) and about 3 months in those with ovarian cancer.

TNBC cohort

Investigators led by Shaveta Vinayak, MD, of the division of oncology at Fred Hutchinson Cancer Research Center, and University of Washington School of Medicine, Seattle Cancer Care Alliance, Seattle, studied 55 patients with TNBC treated with niraparib-pembrolizumab in the trial.

In the efficacy-evaluable population of 47 patients, the objective response rate (ORR) was 21%, and the disease control rate (DCR) was 49%. With a median duration of follow-up of 14.8 months, the median duration of response was not reached.

Activity of the combination varied by tumor BRCA mutation status. Compared with counterparts having BRCA wild-type tumors, patients having tumors with BRCA mutations had a numerically higher ORR (47% vs. 11%), DCR (80% vs. 33%), and PFS (8.3 vs. 2.1 months).

Some 18% of patients had treatment-related anemia, 15% thrombocytopenia, and 7% fatigue. In addition, 15% of patients had immune-related adverse events, with 4% having grade 3 immune-related adverse events.

“Combination niraparib plus pembrolizumab provides promising antitumor activity in patients with advanced or metastatic TNBC, with numerically higher response rates in those with tumor BRCA mutations,” Dr. Vinayak and colleagues conclude. “The combination therapy was safe with a tolerable safety profile, warranting further investigation.”

Ovarian cancer cohort

Investigators led by Panagiotis A. Konstantinopoulos, MD, PhD, of the division of gynecologic oncology, department of medical oncology at Dana-Farber Cancer Institute, Harvard Medical School, Boston, studied 62 patients with ovarian carcinoma treated with niraparib-pembrolizumab in the trial.

In the efficacy-evaluable population of 60 patients, the ORR was 18% and the DCR was 65%. The ORRs were similar regardless of patients’ platinum-based chemotherapy sensitivity, previous bevacizumab treatment, or tumor BRCA or homologous recombination deficiency (HRD) biomarker status.

With a median duration of follow-up of 12.4 months, the median duration of response was not reached, ranging from 4.2 to roughly 14.5 months. Median progression-free survival was 3.4 months.

The leading treatment-related adverse events of grade 3 or higher in this cohort were anemia (21%) and thrombocytopenia (9%). In addition, 19% of patients had immune-related adverse events, with 9% having grade 3 or higher immune-related adverse events.

“Niraparib in combination with pembrolizumab is tolerable, with promising antitumor activity for patients with ovarian carcinoma who have limited treatment options regardless of platinum status, biomarker status, or prior treatment with bevacizumab,” Dr. Konstantinopoulos and colleagues conclude. “Responses in patients without tumor BRCA mutations or non-HRD cancers were higher than expected with either agent as monotherapy.”

Dr. Vinayak disclosed receiving clinical trial funding from TESARO; serving on an advisory board for TESARO; and serving on an advisory board for OncoSec Medical (uncompensated). Dr. Konstantinopoulos disclosed serving on advisory boards for AstraZeneca, Pfizer, and Merck. The trial was supported by TESARO: a GSK company and Merck, and in part by Stand Up to Cancer (a program of the Entertainment Industry Foundation); the Ovarian Cancer Research Fund Alliance; and National Ovarian Cancer Coalition Dream Team Translational Research.

SOURCE: Vinayak A et al. JAMA Oncol. 2019 Jun 13. doi: 10.1001/jamaoncol.2019.1029. Konstantinopoulos PA et al. JAMA Oncol. 2019 Jun 13. doi: 10.1001/jamaoncol.2019.1048.

The strategy of simultaneously exploiting deficient DNA damage repair and unleashing the immune response could expand treatment options for hard-to-treat breast and ovarian cancers, findings of the TOPACIO/KEYNOTE-162 trial suggest.

Triple-negative breast cancer (TNBC) and high-grade serous ovarian carcinoma share a number of genomic features, including a high frequency of BRCA1 and BRCA2 inactivation (Nature. 2012;490:61-70), as well as potential immunoreactivity (Lancet Oncol. 2018;19:40-50).

The open-label, single-arm phase 1/2 trial therefore tested the combination of niraparib (Zejula), an oral poly (ADP-ribose) polymerase (PARP) inhibitor, and pembrolizumab (Keytruda), an antibody to programmed death 1 (PD-1), among more than 100 patients with advanced or metastatic TNBC or recurrent platinum-resistant ovarian carcinoma. Patients were enrolled irrespective of BRCA mutation status or programmed death-ligand 1 (PD-L1) expression.

Main results, reported in JAMA Oncology, showed that the combination was safe, and about a fifth of patients with each type of cancer had an objective response. Median progression-free survival (PFS) was about 2 months in those with TNBC overall (although it exceeded 8 months in the subset with a tumor BRCA mutation) and about 3 months in those with ovarian cancer.

TNBC cohort

Investigators led by Shaveta Vinayak, MD, of the division of oncology at Fred Hutchinson Cancer Research Center, and University of Washington School of Medicine, Seattle Cancer Care Alliance, Seattle, studied 55 patients with TNBC treated with niraparib-pembrolizumab in the trial.

In the efficacy-evaluable population of 47 patients, the objective response rate (ORR) was 21%, and the disease control rate (DCR) was 49%. With a median duration of follow-up of 14.8 months, the median duration of response was not reached.

Activity of the combination varied by tumor BRCA mutation status. Compared with counterparts having BRCA wild-type tumors, patients having tumors with BRCA mutations had a numerically higher ORR (47% vs. 11%), DCR (80% vs. 33%), and PFS (8.3 vs. 2.1 months).

Some 18% of patients had treatment-related anemia, 15% thrombocytopenia, and 7% fatigue. In addition, 15% of patients had immune-related adverse events, with 4% having grade 3 immune-related adverse events.

“Combination niraparib plus pembrolizumab provides promising antitumor activity in patients with advanced or metastatic TNBC, with numerically higher response rates in those with tumor BRCA mutations,” Dr. Vinayak and colleagues conclude. “The combination therapy was safe with a tolerable safety profile, warranting further investigation.”

Ovarian cancer cohort

Investigators led by Panagiotis A. Konstantinopoulos, MD, PhD, of the division of gynecologic oncology, department of medical oncology at Dana-Farber Cancer Institute, Harvard Medical School, Boston, studied 62 patients with ovarian carcinoma treated with niraparib-pembrolizumab in the trial.

In the efficacy-evaluable population of 60 patients, the ORR was 18% and the DCR was 65%. The ORRs were similar regardless of patients’ platinum-based chemotherapy sensitivity, previous bevacizumab treatment, or tumor BRCA or homologous recombination deficiency (HRD) biomarker status.

With a median duration of follow-up of 12.4 months, the median duration of response was not reached, ranging from 4.2 to roughly 14.5 months. Median progression-free survival was 3.4 months.

The leading treatment-related adverse events of grade 3 or higher in this cohort were anemia (21%) and thrombocytopenia (9%). In addition, 19% of patients had immune-related adverse events, with 9% having grade 3 or higher immune-related adverse events.

“Niraparib in combination with pembrolizumab is tolerable, with promising antitumor activity for patients with ovarian carcinoma who have limited treatment options regardless of platinum status, biomarker status, or prior treatment with bevacizumab,” Dr. Konstantinopoulos and colleagues conclude. “Responses in patients without tumor BRCA mutations or non-HRD cancers were higher than expected with either agent as monotherapy.”

Dr. Vinayak disclosed receiving clinical trial funding from TESARO; serving on an advisory board for TESARO; and serving on an advisory board for OncoSec Medical (uncompensated). Dr. Konstantinopoulos disclosed serving on advisory boards for AstraZeneca, Pfizer, and Merck. The trial was supported by TESARO: a GSK company and Merck, and in part by Stand Up to Cancer (a program of the Entertainment Industry Foundation); the Ovarian Cancer Research Fund Alliance; and National Ovarian Cancer Coalition Dream Team Translational Research.

SOURCE: Vinayak A et al. JAMA Oncol. 2019 Jun 13. doi: 10.1001/jamaoncol.2019.1029. Konstantinopoulos PA et al. JAMA Oncol. 2019 Jun 13. doi: 10.1001/jamaoncol.2019.1048.

The strategy of simultaneously exploiting deficient DNA damage repair and unleashing the immune response could expand treatment options for hard-to-treat breast and ovarian cancers, findings of the TOPACIO/KEYNOTE-162 trial suggest.

Triple-negative breast cancer (TNBC) and high-grade serous ovarian carcinoma share a number of genomic features, including a high frequency of BRCA1 and BRCA2 inactivation (Nature. 2012;490:61-70), as well as potential immunoreactivity (Lancet Oncol. 2018;19:40-50).

The open-label, single-arm phase 1/2 trial therefore tested the combination of niraparib (Zejula), an oral poly (ADP-ribose) polymerase (PARP) inhibitor, and pembrolizumab (Keytruda), an antibody to programmed death 1 (PD-1), among more than 100 patients with advanced or metastatic TNBC or recurrent platinum-resistant ovarian carcinoma. Patients were enrolled irrespective of BRCA mutation status or programmed death-ligand 1 (PD-L1) expression.

Main results, reported in JAMA Oncology, showed that the combination was safe, and about a fifth of patients with each type of cancer had an objective response. Median progression-free survival (PFS) was about 2 months in those with TNBC overall (although it exceeded 8 months in the subset with a tumor BRCA mutation) and about 3 months in those with ovarian cancer.

TNBC cohort

Investigators led by Shaveta Vinayak, MD, of the division of oncology at Fred Hutchinson Cancer Research Center, and University of Washington School of Medicine, Seattle Cancer Care Alliance, Seattle, studied 55 patients with TNBC treated with niraparib-pembrolizumab in the trial.

In the efficacy-evaluable population of 47 patients, the objective response rate (ORR) was 21%, and the disease control rate (DCR) was 49%. With a median duration of follow-up of 14.8 months, the median duration of response was not reached.

Activity of the combination varied by tumor BRCA mutation status. Compared with counterparts having BRCA wild-type tumors, patients having tumors with BRCA mutations had a numerically higher ORR (47% vs. 11%), DCR (80% vs. 33%), and PFS (8.3 vs. 2.1 months).

Some 18% of patients had treatment-related anemia, 15% thrombocytopenia, and 7% fatigue. In addition, 15% of patients had immune-related adverse events, with 4% having grade 3 immune-related adverse events.

“Combination niraparib plus pembrolizumab provides promising antitumor activity in patients with advanced or metastatic TNBC, with numerically higher response rates in those with tumor BRCA mutations,” Dr. Vinayak and colleagues conclude. “The combination therapy was safe with a tolerable safety profile, warranting further investigation.”

Ovarian cancer cohort

Investigators led by Panagiotis A. Konstantinopoulos, MD, PhD, of the division of gynecologic oncology, department of medical oncology at Dana-Farber Cancer Institute, Harvard Medical School, Boston, studied 62 patients with ovarian carcinoma treated with niraparib-pembrolizumab in the trial.

In the efficacy-evaluable population of 60 patients, the ORR was 18% and the DCR was 65%. The ORRs were similar regardless of patients’ platinum-based chemotherapy sensitivity, previous bevacizumab treatment, or tumor BRCA or homologous recombination deficiency (HRD) biomarker status.

With a median duration of follow-up of 12.4 months, the median duration of response was not reached, ranging from 4.2 to roughly 14.5 months. Median progression-free survival was 3.4 months.

The leading treatment-related adverse events of grade 3 or higher in this cohort were anemia (21%) and thrombocytopenia (9%). In addition, 19% of patients had immune-related adverse events, with 9% having grade 3 or higher immune-related adverse events.

“Niraparib in combination with pembrolizumab is tolerable, with promising antitumor activity for patients with ovarian carcinoma who have limited treatment options regardless of platinum status, biomarker status, or prior treatment with bevacizumab,” Dr. Konstantinopoulos and colleagues conclude. “Responses in patients without tumor BRCA mutations or non-HRD cancers were higher than expected with either agent as monotherapy.”

Dr. Vinayak disclosed receiving clinical trial funding from TESARO; serving on an advisory board for TESARO; and serving on an advisory board for OncoSec Medical (uncompensated). Dr. Konstantinopoulos disclosed serving on advisory boards for AstraZeneca, Pfizer, and Merck. The trial was supported by TESARO: a GSK company and Merck, and in part by Stand Up to Cancer (a program of the Entertainment Industry Foundation); the Ovarian Cancer Research Fund Alliance; and National Ovarian Cancer Coalition Dream Team Translational Research.

SOURCE: Vinayak A et al. JAMA Oncol. 2019 Jun 13. doi: 10.1001/jamaoncol.2019.1029. Konstantinopoulos PA et al. JAMA Oncol. 2019 Jun 13. doi: 10.1001/jamaoncol.2019.1048.