Will Pass

Approximately one-fifth of patients undergoing hematopoietic stem cell transplantation (HSCT) develop posttraumatic stress disorder (PTSD), based on a retrospective analysis.

Patient factors at time of transplantation, such as low quality of life and high anxiety, predicted PTSD 6 months later, reported lead author Sarah Griffith, MD, of Massachusetts General Hospital, Boston, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

“We know that patients admitted for HSCT are often isolated in the hospital for a prolonged period of time, usually about 3-4 weeks, and that they endure substantial toxicities that impact both their physical and psychological well-being,” Dr. Griffith said. “We also know from the literature that HSCT can be considered a traumatic event and that it may lead to clinically significant PTSD symptoms.” But studies evaluating the prevalence and characteristics of PTSD in this patient population have been lacking, she noted.

Dr. Griffith and her colleagues therefore conducted a retrospective analysis involving 250 adults with hematologic malignancies who underwent autologous or allogeneic HSCT during clinical trials conducted from 2014 to 2016. Median patient age was 56 years.

The first objective of the study was to measure the prevalence of PTSD. The second was to characterize features of PTSD such as intrusion, which entails reliving experiences in the form of nightmares or flashbacks, and hypervigilance, which encompasses insomnia, irritability, and hyperarousal for threat. The third objective was to determine risk factors at baseline.

At time of admission for HSCT, after 2 weeks of hospitalization, and again 6 months after transplantation, patients were evaluated using the Functional Assessment of Cancer Therapy–Bone Marrow Transplant (FACT-BMT), and the Hospital Anxiety and Depression Scale (HADS), which measured of quality of life, anxiety, and depression. Six months after HSCT, patients also underwent screening for PTSD with the Post-Traumatic Stress Checklist (PTSD-CL). Multivariate regression models were used to determine predictive risk factors.

Six months after HSCT, 18.9% of patients had clinically significant PTSD symptoms; most common were symptoms of avoidance (92.3%), hypervigilance (92.3%), and intrusion (76.9%). Among those who did not have clinically significant PTSD, almost one-quarter (24.5%) demonstrated significant hypervigilance, while 13.7% showed symptoms of avoidance.

“Clinically significant PTSD symptoms are common in the transplant population,” Dr. Griffith said.

Baseline predictors of PTSD included single status and lower quality of life. More severe PTSD was predicted by single status, younger age, higher baseline scores for anxiety or depression, and increased anxiety during hospitalization.

Concluding her presentation, Dr. Griffith said that the findings, while correlative and not causative, should prompt concern and intervention.

“It is very important to be aware of and to manage PTSD symptoms in these patients,” she said. “There are several baseline factors that can be identified prior to HSCT that may illuminate patients at risk for developing worse PTSD symptoms down the road, and these patients may benefit from tailored supportive care interventions.”

Specifically, Dr. Griffith recommended integrating palliative care into hospitalization, as this has been shown to reduce anxiety.

In a virtual presentation, invited discussant Nirali N. Shah, MD, of the National Cancer Institute, Bethesda, Md., highlighted the importance of the findings, while also noting that the impact of palliative care on risk of PTSD has yet to be demonstrated.

Dr. Shah suggested that future research may be improved through use of a formal diagnosis for PTSD, instead of a PTSD checklist, as was used in the present study.

“And certainly long-term follow-up would be important to evaluate the utility of this tool looking at symptoms beyond 6 months,” she said.

Dr. Shah went on to discuss the relevance of the findings for pediatric populations, as children may face unique risk factors and consequences related to PTSD.

“[PTSD in children] may be impacted by family dynamics and structure,” Dr. Shah said. “Children may also have significant neurocognitive implications as a result of their underlying disease or prior therapy. They may experience chronic pain as they go out into adulthood and long-term survivorship, and may also struggle with symptoms of anxiety and depression.”

According to Dr. Shah, one previous study involving more than 6,000 adult survivors of childhood cancer found that PTSD was relatively common, with prevalence rate of 9%, suggesting that interventional work is necessary.

“Applying the data in the study from Griffith et al. suggests that evaluation in the more proximal posttransplant period for children is needed to specifically evaluate PTSD and symptoms thereof, and to try to use this to identify an opportunity for intervention,” Dr. Shah said.

“Pediatric-specific assessments are essential to optimally capture disease and/or age-specific considerations,” she added.

The study was funded by the Lymphoma and Leukemia Society. The investigators disclosed additional relationships with Vector Oncology, Pfizer, AstraZeneca, and Gaido Health/BCG Digital Ventures.

SOURCE: Griffith et al. ASCO 2020. Abstract # 7505.

Approximately one-fifth of patients undergoing hematopoietic stem cell transplantation (HSCT) develop posttraumatic stress disorder (PTSD), based on a retrospective analysis.

Patient factors at time of transplantation, such as low quality of life and high anxiety, predicted PTSD 6 months later, reported lead author Sarah Griffith, MD, of Massachusetts General Hospital, Boston, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

“We know that patients admitted for HSCT are often isolated in the hospital for a prolonged period of time, usually about 3-4 weeks, and that they endure substantial toxicities that impact both their physical and psychological well-being,” Dr. Griffith said. “We also know from the literature that HSCT can be considered a traumatic event and that it may lead to clinically significant PTSD symptoms.” But studies evaluating the prevalence and characteristics of PTSD in this patient population have been lacking, she noted.

Dr. Griffith and her colleagues therefore conducted a retrospective analysis involving 250 adults with hematologic malignancies who underwent autologous or allogeneic HSCT during clinical trials conducted from 2014 to 2016. Median patient age was 56 years.

The first objective of the study was to measure the prevalence of PTSD. The second was to characterize features of PTSD such as intrusion, which entails reliving experiences in the form of nightmares or flashbacks, and hypervigilance, which encompasses insomnia, irritability, and hyperarousal for threat. The third objective was to determine risk factors at baseline.

At time of admission for HSCT, after 2 weeks of hospitalization, and again 6 months after transplantation, patients were evaluated using the Functional Assessment of Cancer Therapy–Bone Marrow Transplant (FACT-BMT), and the Hospital Anxiety and Depression Scale (HADS), which measured of quality of life, anxiety, and depression. Six months after HSCT, patients also underwent screening for PTSD with the Post-Traumatic Stress Checklist (PTSD-CL). Multivariate regression models were used to determine predictive risk factors.

Six months after HSCT, 18.9% of patients had clinically significant PTSD symptoms; most common were symptoms of avoidance (92.3%), hypervigilance (92.3%), and intrusion (76.9%). Among those who did not have clinically significant PTSD, almost one-quarter (24.5%) demonstrated significant hypervigilance, while 13.7% showed symptoms of avoidance.

“Clinically significant PTSD symptoms are common in the transplant population,” Dr. Griffith said.

Baseline predictors of PTSD included single status and lower quality of life. More severe PTSD was predicted by single status, younger age, higher baseline scores for anxiety or depression, and increased anxiety during hospitalization.

Concluding her presentation, Dr. Griffith said that the findings, while correlative and not causative, should prompt concern and intervention.

“It is very important to be aware of and to manage PTSD symptoms in these patients,” she said. “There are several baseline factors that can be identified prior to HSCT that may illuminate patients at risk for developing worse PTSD symptoms down the road, and these patients may benefit from tailored supportive care interventions.”

Specifically, Dr. Griffith recommended integrating palliative care into hospitalization, as this has been shown to reduce anxiety.

In a virtual presentation, invited discussant Nirali N. Shah, MD, of the National Cancer Institute, Bethesda, Md., highlighted the importance of the findings, while also noting that the impact of palliative care on risk of PTSD has yet to be demonstrated.

Dr. Shah suggested that future research may be improved through use of a formal diagnosis for PTSD, instead of a PTSD checklist, as was used in the present study.

“And certainly long-term follow-up would be important to evaluate the utility of this tool looking at symptoms beyond 6 months,” she said.

Dr. Shah went on to discuss the relevance of the findings for pediatric populations, as children may face unique risk factors and consequences related to PTSD.

“[PTSD in children] may be impacted by family dynamics and structure,” Dr. Shah said. “Children may also have significant neurocognitive implications as a result of their underlying disease or prior therapy. They may experience chronic pain as they go out into adulthood and long-term survivorship, and may also struggle with symptoms of anxiety and depression.”

According to Dr. Shah, one previous study involving more than 6,000 adult survivors of childhood cancer found that PTSD was relatively common, with prevalence rate of 9%, suggesting that interventional work is necessary.

“Applying the data in the study from Griffith et al. suggests that evaluation in the more proximal posttransplant period for children is needed to specifically evaluate PTSD and symptoms thereof, and to try to use this to identify an opportunity for intervention,” Dr. Shah said.

“Pediatric-specific assessments are essential to optimally capture disease and/or age-specific considerations,” she added.

The study was funded by the Lymphoma and Leukemia Society. The investigators disclosed additional relationships with Vector Oncology, Pfizer, AstraZeneca, and Gaido Health/BCG Digital Ventures.

SOURCE: Griffith et al. ASCO 2020. Abstract # 7505.

Approximately one-fifth of patients undergoing hematopoietic stem cell transplantation (HSCT) develop posttraumatic stress disorder (PTSD), based on a retrospective analysis.

Patient factors at time of transplantation, such as low quality of life and high anxiety, predicted PTSD 6 months later, reported lead author Sarah Griffith, MD, of Massachusetts General Hospital, Boston, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

“We know that patients admitted for HSCT are often isolated in the hospital for a prolonged period of time, usually about 3-4 weeks, and that they endure substantial toxicities that impact both their physical and psychological well-being,” Dr. Griffith said. “We also know from the literature that HSCT can be considered a traumatic event and that it may lead to clinically significant PTSD symptoms.” But studies evaluating the prevalence and characteristics of PTSD in this patient population have been lacking, she noted.

Dr. Griffith and her colleagues therefore conducted a retrospective analysis involving 250 adults with hematologic malignancies who underwent autologous or allogeneic HSCT during clinical trials conducted from 2014 to 2016. Median patient age was 56 years.

The first objective of the study was to measure the prevalence of PTSD. The second was to characterize features of PTSD such as intrusion, which entails reliving experiences in the form of nightmares or flashbacks, and hypervigilance, which encompasses insomnia, irritability, and hyperarousal for threat. The third objective was to determine risk factors at baseline.

At time of admission for HSCT, after 2 weeks of hospitalization, and again 6 months after transplantation, patients were evaluated using the Functional Assessment of Cancer Therapy–Bone Marrow Transplant (FACT-BMT), and the Hospital Anxiety and Depression Scale (HADS), which measured of quality of life, anxiety, and depression. Six months after HSCT, patients also underwent screening for PTSD with the Post-Traumatic Stress Checklist (PTSD-CL). Multivariate regression models were used to determine predictive risk factors.

Six months after HSCT, 18.9% of patients had clinically significant PTSD symptoms; most common were symptoms of avoidance (92.3%), hypervigilance (92.3%), and intrusion (76.9%). Among those who did not have clinically significant PTSD, almost one-quarter (24.5%) demonstrated significant hypervigilance, while 13.7% showed symptoms of avoidance.

“Clinically significant PTSD symptoms are common in the transplant population,” Dr. Griffith said.

Baseline predictors of PTSD included single status and lower quality of life. More severe PTSD was predicted by single status, younger age, higher baseline scores for anxiety or depression, and increased anxiety during hospitalization.

Concluding her presentation, Dr. Griffith said that the findings, while correlative and not causative, should prompt concern and intervention.

“It is very important to be aware of and to manage PTSD symptoms in these patients,” she said. “There are several baseline factors that can be identified prior to HSCT that may illuminate patients at risk for developing worse PTSD symptoms down the road, and these patients may benefit from tailored supportive care interventions.”

Specifically, Dr. Griffith recommended integrating palliative care into hospitalization, as this has been shown to reduce anxiety.

In a virtual presentation, invited discussant Nirali N. Shah, MD, of the National Cancer Institute, Bethesda, Md., highlighted the importance of the findings, while also noting that the impact of palliative care on risk of PTSD has yet to be demonstrated.

Dr. Shah suggested that future research may be improved through use of a formal diagnosis for PTSD, instead of a PTSD checklist, as was used in the present study.

“And certainly long-term follow-up would be important to evaluate the utility of this tool looking at symptoms beyond 6 months,” she said.

Dr. Shah went on to discuss the relevance of the findings for pediatric populations, as children may face unique risk factors and consequences related to PTSD.

“[PTSD in children] may be impacted by family dynamics and structure,” Dr. Shah said. “Children may also have significant neurocognitive implications as a result of their underlying disease or prior therapy. They may experience chronic pain as they go out into adulthood and long-term survivorship, and may also struggle with symptoms of anxiety and depression.”

According to Dr. Shah, one previous study involving more than 6,000 adult survivors of childhood cancer found that PTSD was relatively common, with prevalence rate of 9%, suggesting that interventional work is necessary.

“Applying the data in the study from Griffith et al. suggests that evaluation in the more proximal posttransplant period for children is needed to specifically evaluate PTSD and symptoms thereof, and to try to use this to identify an opportunity for intervention,” Dr. Shah said.

“Pediatric-specific assessments are essential to optimally capture disease and/or age-specific considerations,” she added.

The study was funded by the Lymphoma and Leukemia Society. The investigators disclosed additional relationships with Vector Oncology, Pfizer, AstraZeneca, and Gaido Health/BCG Digital Ventures.

SOURCE: Griffith et al. ASCO 2020. Abstract # 7505.

A disease risk index is now available for pediatric patients with acute myeloid leukemia or acute lymphoblastic leukemia who undergo allogeneic hematopoietic stem cell transplantation.

The model, which was developed and validated using data from more than 2,000 patients, stratifies probabilities of leukemia-free survival (LFS) into four risk groups for acute myeloid leukemia (AML) and three risk groups for acute lymphoblastic leukemia (ALL), reported lead author Muna Qayed, MD, of Emory University, Atlanta, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

“The outcome of stem cell transplantation for hematologic malignancy is influenced by disease type, cytogenetics, and disease status at transplantation,” Dr. Qayed said. “In adults, these attributes were used to develop the disease risk index, or DRI, that can stratify patients for overall survival for purposes such as prognostication or clinical trial entry.”

But no such model exists for pediatric patients, Dr. Qayed said, noting that the adult DRI was found to be inaccurate when applied to children.

“[T]he [adult] DRI did not differentiate [pediatric] patients by overall survival,” Dr. Qayed said. “Therefore, knowing that pediatric AML and ALL differ biologically from adult leukemia, and further, treatment strategies differ between adults and children, we aimed to develop a pediatric-specific DRI.”

This involved analysis of data from 1,135 children with AML and 1,228 children with ALL who underwent transplantation between 2008 and 2017. All patients had myeloablative conditioning, and 75% received an unrelated donor graft. Haploidentical transplants were excluded because of small sample size.

Analyses were conducted in AML and ALL cohorts, with patients in each population randomized to training and validation subgroups in a 1:1 ratio. The primary outcome was LFS. Cox regression models were used to identify significant characteristics, which were then integrated into a prognostic scoring system for the training groups. These scoring systems were then tested in the validation subgroups. Maximum likelihood was used to identify age cutoffs, which were 3 years for AML and 2 years for ALL.

In both cohorts, disease status at transplantation was characterized by complete remission and minimal residual disease status.

In the AML cohort, approximately one-third of patients were in first complete remission with negative minimal residual disease. Risk was stratified into four groups, including good, intermediate, high, and very high risk, with respective 5-year LFS probabilities of 81%, 56%, 44%, and 21%. Independent predictors of poorer outcome included unfavorable cytogenetics, first or second complete remission with minimal residual disease positivity, relapse at transplantation, and age less than 3 years.

In the ALL cohort, risk was stratified into three risk tiers: good, intermediate, and high, with 5-year LFS probabilities of 68%, 50%, and 15%, respectively. Independent predictors of poorer outcome included age less than 2 years, relapse at transplantation, and second complete remission regardless of minimal residual disease status.

The models for each disease also predicted overall survival.

For AML, hazard ratios, ascending from good to very-high-risk tiers, were 1.00, 3.52, 4.67, and 8.62. For ALL risk tiers, ascending hazard ratios were 1.00, 2.16, and 3.86.

“In summary, the pediatric disease risk index validated for leukemia-free survival and overall survival successfully stratifies children with acute leukemia at the time of transplantation,” Dr. Qayed said.

She concluded her presentation by highlighting the practicality and relevance of the new scoring system.

“The components included in the scoring system used information that is readily available pretransplantation, lending support to the deliverability of the prognostic scoring system,” Dr. Qayed said. “It can further be used for improved interpretation of multicenter data and in clinical trials for risk stratification.”

In a virtual presentation, invited discussant Nirali N. Shah, MD, of the National Cancer Institute, Bethesda, Md., first emphasized the clinical importance of an accurate disease risk index for pediatric patients.

“When going into transplant, the No. 1 question that all parents will ask is: ‘Will my child be cured?’ ” she said.

According to Dr. Shah, the risk model developed by Dr. Qayed and colleagues is built on a strong foundation, including adequate sample size, comprehensive disease characterization, exclusion of patients that did not undergo myeloablative conditioning, and use of minimal residual disease status.

Still, more work is needed, Dr. Shah said.

“This DRI will need to be prospectively tested and compared to other established risk factors. For instance, minimal residual disease alone can be further stratified and has a significant role in establishing risk for posttransplant relapse. And the development of acute graft-versus-host disease also plays an important role in posttransplant relapse.”

Dr. Shah went on to outline potential areas of improvement.

“[F]uture directions for this study could include incorporation of early posttransplant events like graft-versus-host disease, potential stratification of the minimal residual disease results among those patients in complete remission, and potential application of this DRI to the adolescent and young adult population, which may have slight variation even from the adult DRI.”The study was funded by the National Institutes of Health. The investigators disclosed no conflicts of interest

SOURCE: Qayed M et al. ASCO 2020, Abstract 7503.

A disease risk index is now available for pediatric patients with acute myeloid leukemia or acute lymphoblastic leukemia who undergo allogeneic hematopoietic stem cell transplantation.

The model, which was developed and validated using data from more than 2,000 patients, stratifies probabilities of leukemia-free survival (LFS) into four risk groups for acute myeloid leukemia (AML) and three risk groups for acute lymphoblastic leukemia (ALL), reported lead author Muna Qayed, MD, of Emory University, Atlanta, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

“The outcome of stem cell transplantation for hematologic malignancy is influenced by disease type, cytogenetics, and disease status at transplantation,” Dr. Qayed said. “In adults, these attributes were used to develop the disease risk index, or DRI, that can stratify patients for overall survival for purposes such as prognostication or clinical trial entry.”

But no such model exists for pediatric patients, Dr. Qayed said, noting that the adult DRI was found to be inaccurate when applied to children.

“[T]he [adult] DRI did not differentiate [pediatric] patients by overall survival,” Dr. Qayed said. “Therefore, knowing that pediatric AML and ALL differ biologically from adult leukemia, and further, treatment strategies differ between adults and children, we aimed to develop a pediatric-specific DRI.”

This involved analysis of data from 1,135 children with AML and 1,228 children with ALL who underwent transplantation between 2008 and 2017. All patients had myeloablative conditioning, and 75% received an unrelated donor graft. Haploidentical transplants were excluded because of small sample size.

Analyses were conducted in AML and ALL cohorts, with patients in each population randomized to training and validation subgroups in a 1:1 ratio. The primary outcome was LFS. Cox regression models were used to identify significant characteristics, which were then integrated into a prognostic scoring system for the training groups. These scoring systems were then tested in the validation subgroups. Maximum likelihood was used to identify age cutoffs, which were 3 years for AML and 2 years for ALL.

In both cohorts, disease status at transplantation was characterized by complete remission and minimal residual disease status.

In the AML cohort, approximately one-third of patients were in first complete remission with negative minimal residual disease. Risk was stratified into four groups, including good, intermediate, high, and very high risk, with respective 5-year LFS probabilities of 81%, 56%, 44%, and 21%. Independent predictors of poorer outcome included unfavorable cytogenetics, first or second complete remission with minimal residual disease positivity, relapse at transplantation, and age less than 3 years.

In the ALL cohort, risk was stratified into three risk tiers: good, intermediate, and high, with 5-year LFS probabilities of 68%, 50%, and 15%, respectively. Independent predictors of poorer outcome included age less than 2 years, relapse at transplantation, and second complete remission regardless of minimal residual disease status.

The models for each disease also predicted overall survival.

For AML, hazard ratios, ascending from good to very-high-risk tiers, were 1.00, 3.52, 4.67, and 8.62. For ALL risk tiers, ascending hazard ratios were 1.00, 2.16, and 3.86.

“In summary, the pediatric disease risk index validated for leukemia-free survival and overall survival successfully stratifies children with acute leukemia at the time of transplantation,” Dr. Qayed said.

She concluded her presentation by highlighting the practicality and relevance of the new scoring system.

“The components included in the scoring system used information that is readily available pretransplantation, lending support to the deliverability of the prognostic scoring system,” Dr. Qayed said. “It can further be used for improved interpretation of multicenter data and in clinical trials for risk stratification.”

In a virtual presentation, invited discussant Nirali N. Shah, MD, of the National Cancer Institute, Bethesda, Md., first emphasized the clinical importance of an accurate disease risk index for pediatric patients.

“When going into transplant, the No. 1 question that all parents will ask is: ‘Will my child be cured?’ ” she said.

According to Dr. Shah, the risk model developed by Dr. Qayed and colleagues is built on a strong foundation, including adequate sample size, comprehensive disease characterization, exclusion of patients that did not undergo myeloablative conditioning, and use of minimal residual disease status.

Still, more work is needed, Dr. Shah said.

“This DRI will need to be prospectively tested and compared to other established risk factors. For instance, minimal residual disease alone can be further stratified and has a significant role in establishing risk for posttransplant relapse. And the development of acute graft-versus-host disease also plays an important role in posttransplant relapse.”

Dr. Shah went on to outline potential areas of improvement.

“[F]uture directions for this study could include incorporation of early posttransplant events like graft-versus-host disease, potential stratification of the minimal residual disease results among those patients in complete remission, and potential application of this DRI to the adolescent and young adult population, which may have slight variation even from the adult DRI.”The study was funded by the National Institutes of Health. The investigators disclosed no conflicts of interest

SOURCE: Qayed M et al. ASCO 2020, Abstract 7503.

A disease risk index is now available for pediatric patients with acute myeloid leukemia or acute lymphoblastic leukemia who undergo allogeneic hematopoietic stem cell transplantation.

The model, which was developed and validated using data from more than 2,000 patients, stratifies probabilities of leukemia-free survival (LFS) into four risk groups for acute myeloid leukemia (AML) and three risk groups for acute lymphoblastic leukemia (ALL), reported lead author Muna Qayed, MD, of Emory University, Atlanta, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

“The outcome of stem cell transplantation for hematologic malignancy is influenced by disease type, cytogenetics, and disease status at transplantation,” Dr. Qayed said. “In adults, these attributes were used to develop the disease risk index, or DRI, that can stratify patients for overall survival for purposes such as prognostication or clinical trial entry.”

But no such model exists for pediatric patients, Dr. Qayed said, noting that the adult DRI was found to be inaccurate when applied to children.

“[T]he [adult] DRI did not differentiate [pediatric] patients by overall survival,” Dr. Qayed said. “Therefore, knowing that pediatric AML and ALL differ biologically from adult leukemia, and further, treatment strategies differ between adults and children, we aimed to develop a pediatric-specific DRI.”

This involved analysis of data from 1,135 children with AML and 1,228 children with ALL who underwent transplantation between 2008 and 2017. All patients had myeloablative conditioning, and 75% received an unrelated donor graft. Haploidentical transplants were excluded because of small sample size.

Analyses were conducted in AML and ALL cohorts, with patients in each population randomized to training and validation subgroups in a 1:1 ratio. The primary outcome was LFS. Cox regression models were used to identify significant characteristics, which were then integrated into a prognostic scoring system for the training groups. These scoring systems were then tested in the validation subgroups. Maximum likelihood was used to identify age cutoffs, which were 3 years for AML and 2 years for ALL.

In both cohorts, disease status at transplantation was characterized by complete remission and minimal residual disease status.

In the AML cohort, approximately one-third of patients were in first complete remission with negative minimal residual disease. Risk was stratified into four groups, including good, intermediate, high, and very high risk, with respective 5-year LFS probabilities of 81%, 56%, 44%, and 21%. Independent predictors of poorer outcome included unfavorable cytogenetics, first or second complete remission with minimal residual disease positivity, relapse at transplantation, and age less than 3 years.

In the ALL cohort, risk was stratified into three risk tiers: good, intermediate, and high, with 5-year LFS probabilities of 68%, 50%, and 15%, respectively. Independent predictors of poorer outcome included age less than 2 years, relapse at transplantation, and second complete remission regardless of minimal residual disease status.

The models for each disease also predicted overall survival.

For AML, hazard ratios, ascending from good to very-high-risk tiers, were 1.00, 3.52, 4.67, and 8.62. For ALL risk tiers, ascending hazard ratios were 1.00, 2.16, and 3.86.

“In summary, the pediatric disease risk index validated for leukemia-free survival and overall survival successfully stratifies children with acute leukemia at the time of transplantation,” Dr. Qayed said.

She concluded her presentation by highlighting the practicality and relevance of the new scoring system.

“The components included in the scoring system used information that is readily available pretransplantation, lending support to the deliverability of the prognostic scoring system,” Dr. Qayed said. “It can further be used for improved interpretation of multicenter data and in clinical trials for risk stratification.”

In a virtual presentation, invited discussant Nirali N. Shah, MD, of the National Cancer Institute, Bethesda, Md., first emphasized the clinical importance of an accurate disease risk index for pediatric patients.

“When going into transplant, the No. 1 question that all parents will ask is: ‘Will my child be cured?’ ” she said.

According to Dr. Shah, the risk model developed by Dr. Qayed and colleagues is built on a strong foundation, including adequate sample size, comprehensive disease characterization, exclusion of patients that did not undergo myeloablative conditioning, and use of minimal residual disease status.

Still, more work is needed, Dr. Shah said.

“This DRI will need to be prospectively tested and compared to other established risk factors. For instance, minimal residual disease alone can be further stratified and has a significant role in establishing risk for posttransplant relapse. And the development of acute graft-versus-host disease also plays an important role in posttransplant relapse.”

Dr. Shah went on to outline potential areas of improvement.

“[F]uture directions for this study could include incorporation of early posttransplant events like graft-versus-host disease, potential stratification of the minimal residual disease results among those patients in complete remission, and potential application of this DRI to the adolescent and young adult population, which may have slight variation even from the adult DRI.”The study was funded by the National Institutes of Health. The investigators disclosed no conflicts of interest

SOURCE: Qayed M et al. ASCO 2020, Abstract 7503.

For patients with newly diagnosed, high-risk diffuse large B-cell lymphoma (DLBCL), adding avadomide to standard therapy may reduce the likelihood of treatment failure, based on phase 1 results.

The regimen was well tolerated and had a complete response rate of 79%, reported lead author Neha Mehta-Shah, MD, of Washington University, St. Louis, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

Newly diagnosed DLBCL “remains a clinical challenge,” Dr. Mehta-Shah said, noting a treatment failure rate of 30%-50% for standard rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days (R-CHOP-21), and worse outcomes among patients with high-risk disease.

In an effort to boost efficacy, the investigators turned to avadomide, a cereblon E3 ligase modulator, which previously demonstrated a complete response rate of 11% when used as monotherapy for patients with relapsed or refractory DLBCL.

The present phase 1 data included 35 adults with newly diagnosed DLBCL who had measurable lesions of at least 2.0 cm and International Prognostic Indices (IPI) between 3-5. Specifically, 51% of patients had an IPI of 3, while 49% had an IPI of 4-5.

All patients received standard R-CHOP with pegfilgrastim (to stimulate white blood cell growth), plus escalating doses of oral avadomide from 1-3 mg. Treatment was delivered, when tolerated, for up to six 21-day cycles. Depending on dose level, avadomide was given during either 2 or 3 out of 3 weeks. During treatment weeks, avadomide was given on 5 of 7 days.

The primary objectives were safety, tolerability, and complete response rate. Secondary objectives included biomarkers and additional efficacy measures, while exploratory analyses were also conducted to assess pharmacokinetics and pharmacodynamics.

Out of 34 patients evaluable for efficacy, the complete response rate was 79% and the objective response rate was 88%. After a median follow-up of 10 months, the 1-year progression-free survival rate was 80%.

“The combination showed promising efficacy,” Dr. Mehta-Shah said.

The regimen was also well tolerated and demonstrated an “acceptable safety profile consistent with either therapy alone,” Dr. Mehta-Shah added.

Most patients (91%) completed all six cycles of therapy. Median relative total dose intensities were 99% and 95% for avadomide and R-CHOP-21, respectively. Approximately two out of three patients (66%) required dose interruptions of avadomide, and 9% required dose reductions because of adverse events.

Dose-limiting toxicities occurred in six patients, including sepsis, febrile neutropenia caused by skin infections, febrile neutropenia with hypotension, febrile neutropenia, pneumonia, and neutropenia with bacterial hepatic infection. Based on these findings, the recommended phase 2 dose of avadomide was determined to be 3 mg given during 2 out of 3 weeks.

About 74% of patients had grade 3-4 treatment-emergent adverse events, the most common of which were neutropenia (54%), anemia (20%), leukopenia (20%), lymphopenia (14%), hypophosphatemia (14%), and febrile neutropenia (11%).

During the second cycle of therapy, one patient died because of concurrent pneumonia. After completion of therapy, two patients developed cardiac failure, and data gathered after each cycle showed that five patients had developed elevated levels of troponin or brain natriuretic peptide.

Flow cytometry showed that avadomide had proimmunomodulatory effects, including expansion of memory T-cell populations and enhanced proliferation of T cells and NK cells. The magnitude of this latter increase was greater than that observed in previous studies involving R-CHOP and durvalumab, Dr. Mehta-Shah noted.

“We look forward to following up on this data regarding the progression-free survival over a longer period of time,” Dr. Mehta-Shah said. “The results of this trial indicate that further evaluation of cereblon-modulating compounds combined with immunochemotherapy for patients with previously untreated diffuse large B-cell lymphoma is worthy of further exploration.”

Invited discussant Edward Yeh, MD, of the University of Missouri–Columbia, called cereblon modulators such as avadomide and thalidomide a “very exciting class of anticancer therapy.”

In a virtual presentation, Dr. Yeh noted that cereblon modulators have several advantages, including “good absorption, distribution, metabolism, [and] elimination,” plus relatively low susceptibility to mutation-directed drug resistance.

Despite some drawbacks, including difficulty to design and synthesize, Dr. Yeh suggested that this drug class may play a bigger role over time.

“We’re expecting more cancer therapy to come to fruition through the utilization of this posttranslational, protein-modification pathway,” he concluded.

The study was funded by Celgene. The investigators disclosed additional relationships with Kyowa Hakko Kirin, AstraZeneca, Roche, and others.

SOURCE: Mehta-Shah N et al. ASCO 2020, Abstract 3501.

For patients with newly diagnosed, high-risk diffuse large B-cell lymphoma (DLBCL), adding avadomide to standard therapy may reduce the likelihood of treatment failure, based on phase 1 results.

The regimen was well tolerated and had a complete response rate of 79%, reported lead author Neha Mehta-Shah, MD, of Washington University, St. Louis, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

Newly diagnosed DLBCL “remains a clinical challenge,” Dr. Mehta-Shah said, noting a treatment failure rate of 30%-50% for standard rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days (R-CHOP-21), and worse outcomes among patients with high-risk disease.

In an effort to boost efficacy, the investigators turned to avadomide, a cereblon E3 ligase modulator, which previously demonstrated a complete response rate of 11% when used as monotherapy for patients with relapsed or refractory DLBCL.

The present phase 1 data included 35 adults with newly diagnosed DLBCL who had measurable lesions of at least 2.0 cm and International Prognostic Indices (IPI) between 3-5. Specifically, 51% of patients had an IPI of 3, while 49% had an IPI of 4-5.

All patients received standard R-CHOP with pegfilgrastim (to stimulate white blood cell growth), plus escalating doses of oral avadomide from 1-3 mg. Treatment was delivered, when tolerated, for up to six 21-day cycles. Depending on dose level, avadomide was given during either 2 or 3 out of 3 weeks. During treatment weeks, avadomide was given on 5 of 7 days.

The primary objectives were safety, tolerability, and complete response rate. Secondary objectives included biomarkers and additional efficacy measures, while exploratory analyses were also conducted to assess pharmacokinetics and pharmacodynamics.

Out of 34 patients evaluable for efficacy, the complete response rate was 79% and the objective response rate was 88%. After a median follow-up of 10 months, the 1-year progression-free survival rate was 80%.

“The combination showed promising efficacy,” Dr. Mehta-Shah said.

The regimen was also well tolerated and demonstrated an “acceptable safety profile consistent with either therapy alone,” Dr. Mehta-Shah added.

Most patients (91%) completed all six cycles of therapy. Median relative total dose intensities were 99% and 95% for avadomide and R-CHOP-21, respectively. Approximately two out of three patients (66%) required dose interruptions of avadomide, and 9% required dose reductions because of adverse events.

Dose-limiting toxicities occurred in six patients, including sepsis, febrile neutropenia caused by skin infections, febrile neutropenia with hypotension, febrile neutropenia, pneumonia, and neutropenia with bacterial hepatic infection. Based on these findings, the recommended phase 2 dose of avadomide was determined to be 3 mg given during 2 out of 3 weeks.

About 74% of patients had grade 3-4 treatment-emergent adverse events, the most common of which were neutropenia (54%), anemia (20%), leukopenia (20%), lymphopenia (14%), hypophosphatemia (14%), and febrile neutropenia (11%).

During the second cycle of therapy, one patient died because of concurrent pneumonia. After completion of therapy, two patients developed cardiac failure, and data gathered after each cycle showed that five patients had developed elevated levels of troponin or brain natriuretic peptide.

Flow cytometry showed that avadomide had proimmunomodulatory effects, including expansion of memory T-cell populations and enhanced proliferation of T cells and NK cells. The magnitude of this latter increase was greater than that observed in previous studies involving R-CHOP and durvalumab, Dr. Mehta-Shah noted.

“We look forward to following up on this data regarding the progression-free survival over a longer period of time,” Dr. Mehta-Shah said. “The results of this trial indicate that further evaluation of cereblon-modulating compounds combined with immunochemotherapy for patients with previously untreated diffuse large B-cell lymphoma is worthy of further exploration.”

Invited discussant Edward Yeh, MD, of the University of Missouri–Columbia, called cereblon modulators such as avadomide and thalidomide a “very exciting class of anticancer therapy.”

In a virtual presentation, Dr. Yeh noted that cereblon modulators have several advantages, including “good absorption, distribution, metabolism, [and] elimination,” plus relatively low susceptibility to mutation-directed drug resistance.

Despite some drawbacks, including difficulty to design and synthesize, Dr. Yeh suggested that this drug class may play a bigger role over time.

“We’re expecting more cancer therapy to come to fruition through the utilization of this posttranslational, protein-modification pathway,” he concluded.

The study was funded by Celgene. The investigators disclosed additional relationships with Kyowa Hakko Kirin, AstraZeneca, Roche, and others.

SOURCE: Mehta-Shah N et al. ASCO 2020, Abstract 3501.

For patients with newly diagnosed, high-risk diffuse large B-cell lymphoma (DLBCL), adding avadomide to standard therapy may reduce the likelihood of treatment failure, based on phase 1 results.

The regimen was well tolerated and had a complete response rate of 79%, reported lead author Neha Mehta-Shah, MD, of Washington University, St. Louis, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

Newly diagnosed DLBCL “remains a clinical challenge,” Dr. Mehta-Shah said, noting a treatment failure rate of 30%-50% for standard rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days (R-CHOP-21), and worse outcomes among patients with high-risk disease.

In an effort to boost efficacy, the investigators turned to avadomide, a cereblon E3 ligase modulator, which previously demonstrated a complete response rate of 11% when used as monotherapy for patients with relapsed or refractory DLBCL.

The present phase 1 data included 35 adults with newly diagnosed DLBCL who had measurable lesions of at least 2.0 cm and International Prognostic Indices (IPI) between 3-5. Specifically, 51% of patients had an IPI of 3, while 49% had an IPI of 4-5.

All patients received standard R-CHOP with pegfilgrastim (to stimulate white blood cell growth), plus escalating doses of oral avadomide from 1-3 mg. Treatment was delivered, when tolerated, for up to six 21-day cycles. Depending on dose level, avadomide was given during either 2 or 3 out of 3 weeks. During treatment weeks, avadomide was given on 5 of 7 days.

The primary objectives were safety, tolerability, and complete response rate. Secondary objectives included biomarkers and additional efficacy measures, while exploratory analyses were also conducted to assess pharmacokinetics and pharmacodynamics.

Out of 34 patients evaluable for efficacy, the complete response rate was 79% and the objective response rate was 88%. After a median follow-up of 10 months, the 1-year progression-free survival rate was 80%.

“The combination showed promising efficacy,” Dr. Mehta-Shah said.

The regimen was also well tolerated and demonstrated an “acceptable safety profile consistent with either therapy alone,” Dr. Mehta-Shah added.

Most patients (91%) completed all six cycles of therapy. Median relative total dose intensities were 99% and 95% for avadomide and R-CHOP-21, respectively. Approximately two out of three patients (66%) required dose interruptions of avadomide, and 9% required dose reductions because of adverse events.

Dose-limiting toxicities occurred in six patients, including sepsis, febrile neutropenia caused by skin infections, febrile neutropenia with hypotension, febrile neutropenia, pneumonia, and neutropenia with bacterial hepatic infection. Based on these findings, the recommended phase 2 dose of avadomide was determined to be 3 mg given during 2 out of 3 weeks.

About 74% of patients had grade 3-4 treatment-emergent adverse events, the most common of which were neutropenia (54%), anemia (20%), leukopenia (20%), lymphopenia (14%), hypophosphatemia (14%), and febrile neutropenia (11%).

During the second cycle of therapy, one patient died because of concurrent pneumonia. After completion of therapy, two patients developed cardiac failure, and data gathered after each cycle showed that five patients had developed elevated levels of troponin or brain natriuretic peptide.

Flow cytometry showed that avadomide had proimmunomodulatory effects, including expansion of memory T-cell populations and enhanced proliferation of T cells and NK cells. The magnitude of this latter increase was greater than that observed in previous studies involving R-CHOP and durvalumab, Dr. Mehta-Shah noted.

“We look forward to following up on this data regarding the progression-free survival over a longer period of time,” Dr. Mehta-Shah said. “The results of this trial indicate that further evaluation of cereblon-modulating compounds combined with immunochemotherapy for patients with previously untreated diffuse large B-cell lymphoma is worthy of further exploration.”

Invited discussant Edward Yeh, MD, of the University of Missouri–Columbia, called cereblon modulators such as avadomide and thalidomide a “very exciting class of anticancer therapy.”

In a virtual presentation, Dr. Yeh noted that cereblon modulators have several advantages, including “good absorption, distribution, metabolism, [and] elimination,” plus relatively low susceptibility to mutation-directed drug resistance.

Despite some drawbacks, including difficulty to design and synthesize, Dr. Yeh suggested that this drug class may play a bigger role over time.

“We’re expecting more cancer therapy to come to fruition through the utilization of this posttranslational, protein-modification pathway,” he concluded.

The study was funded by Celgene. The investigators disclosed additional relationships with Kyowa Hakko Kirin, AstraZeneca, Roche, and others.

SOURCE: Mehta-Shah N et al. ASCO 2020, Abstract 3501.

Addressing local supply constraints may be insufficient to improve poorer outcomes among women who need a liver transplant, based on a large retrospective analysis.

Sex-based disparities in liver allocation were more strongly associated with liver size mismatch and MELD (Model for End-stage Liver Disease) score than geographic factors, reported lead author Jayme E. Locke, MD, of the University of Alabama at Birmingham, and colleagues.

“Currently, the transplant community is considering geographic redistribution ... to redefine local organ supply by replacing donor service areas with fixed concentric circles around donor hospitals,” the investigators wrote in JAMA Surgery. “However, newly proposed geographic models rely on the same metric for medical urgency, the MELD score, and offer no solution for candidates with small body stature who may appear at the top of the match run yet are routinely skipped secondary to discrepancies in donor-recipient size.”

To further investigate the driving forces behind sex-based disparities, the investigators conducted the first national study of its kind, involving 81,357 adults who were wait-listed for liver transplant. Primary outcomes included deceased donor liver transplant and wait list mortality. Using multivariate regression models and inverse odds ratio weighting, the investigators determined proportions of disparity shared across MELD score, candidate anthropometric and liver measurements, and geographic location.

Compared with men, women were 14.4% less likely to receive a transplant, and 8.6% more likely to die on the wait list.

The only geographic factor significantly associated with the increased disparity between female sex and wait list mortality was organ procurement organization, which was associated with a 22% increase. The disparity between rates of transplant receipt was not linked with any geographic factors.

In contrast, MELD score accounted for increases in disparity of 10.3% and 50.1% for organ receipt and wait list mortality, respectively. Candidate anthropometric and liver measurements played an even greater role, raising disparity by 49.0% for organ receipt and 125.8% for wait list mortality.

“Size mismatch between the donor and intended recipient and incorrect assessments of liver disease severity were more strongly associated with the observed sex disparity in wait list mortality than local supply of organs,” the investigators wrote.

Dr. Locke and colleagues noted that ongoing debates about geographic disparity hinge upon the assumption that the MELD score accurately measures disease severity, despite known shortcomings, including reliance upon serum creatinine level, which is influenced by muscle mass and therefore overestimates kidney function in women, and sex-based differences in size, which the MELD score does not incorporate whatsoever.

As such, the investigators suggested that addressing issues with the MELD score and organ size mismatch should be part of a more comprehensive approach to fixing sex-based disparities among candidates for liver transplant.

“Although geographic factors matter, examining geographic access alone may be insufficient,” they concluded.

James F. Markmann, MD, PhD, chief of the division of transplantation at Massachusetts General Hospital, Boston, who has previously published research in support of geographic redistribution, said in an interview that the study by Dr. Locke and colleagues “highlights a well-known problem in the liver transplant field.”

“The cause of this disparity is nicely illustrated by Dr. Locke’s work, which shows multiple contributing factors,” Dr. Markmann said.

While Dr. Markmann agreed with Dr. Locke and colleagues’ proposal that estimated glomerular filtration rate, instead of creatinine, could be used to more accurately measure renal function across sexes, he suggested that the disparities uncovered by their analysis are more likely driven by body size than sex.

“A more impactful factor and one obvious to those performing transplants is that on average the smaller body habitus of females makes more organs unsuitable due to size mismatch,” Dr. Markmann said. “In general, it is technically much less of a barrier to put a small liver into a large patient, than a large liver in a small patient. But, the same disparity in access almost certainly applies to small males; unfortunately, the authors did not examine this point. If allocation changes are envisioned to gain greater fairness in organ access, at least for the recipient size issue, it should be a size issue and not a sex issue.”

Dr. Markmann went on to explain that steps are currently being taken to make liver access more equitable.

“As of February 4th of this year, a broader sharing program for deceased donor livers was implemented,” he said. “This will make more organs available to those in greatest need. It will also potentially increase the number of liver offers to sick patients with a small body habitus and will hopefully reduce the excess morbidity and mortality they suffer.”

According to Willscott E. Naugler, MD and Susan L. Orloff, MD, of Oregon Health & Science University, Portland, novel clinical strategies need to be reinforced with a broader mindset in order to close the gap between men and women.

“A change in the MELD score is unlikely to fix this problem,” they wrote in an accompanying JAMA Surgery editorial, “but it is not hard to think of solutions; one could imagine, for example, allowing women of small stature to access pediatric livers while ramping up liver splits to increase contributions to the pediatric pool.”

Dr. Naugler and Dr. Orloff went on to suggest that barriers to equity may be culturally insidious.

“It is likely that the same unconscious biases that lead us to pay women surgeons less account for the lack of will to make these simple changes,” they wrote. “Not mentioned are multiple sociocultural elements that favor men over women in organ transplant. ... These realities cannot be fixed with changes to the MELD score, and we must be mindful not to let such notions distract from the essential hard work of creating long-lasting cultural changes that underpin a true path forward.”

The investigators disclosed relationships with Sanofi, Hansa Medical, Natera, and others.

SOURCE: Locke JE et al. JAMA Surg. 2020 May 20. doi: 10.1001/jamasurg.2020.1129.

Addressing local supply constraints may be insufficient to improve poorer outcomes among women who need a liver transplant, based on a large retrospective analysis.

Sex-based disparities in liver allocation were more strongly associated with liver size mismatch and MELD (Model for End-stage Liver Disease) score than geographic factors, reported lead author Jayme E. Locke, MD, of the University of Alabama at Birmingham, and colleagues.

“Currently, the transplant community is considering geographic redistribution ... to redefine local organ supply by replacing donor service areas with fixed concentric circles around donor hospitals,” the investigators wrote in JAMA Surgery. “However, newly proposed geographic models rely on the same metric for medical urgency, the MELD score, and offer no solution for candidates with small body stature who may appear at the top of the match run yet are routinely skipped secondary to discrepancies in donor-recipient size.”

To further investigate the driving forces behind sex-based disparities, the investigators conducted the first national study of its kind, involving 81,357 adults who were wait-listed for liver transplant. Primary outcomes included deceased donor liver transplant and wait list mortality. Using multivariate regression models and inverse odds ratio weighting, the investigators determined proportions of disparity shared across MELD score, candidate anthropometric and liver measurements, and geographic location.

Compared with men, women were 14.4% less likely to receive a transplant, and 8.6% more likely to die on the wait list.

The only geographic factor significantly associated with the increased disparity between female sex and wait list mortality was organ procurement organization, which was associated with a 22% increase. The disparity between rates of transplant receipt was not linked with any geographic factors.

In contrast, MELD score accounted for increases in disparity of 10.3% and 50.1% for organ receipt and wait list mortality, respectively. Candidate anthropometric and liver measurements played an even greater role, raising disparity by 49.0% for organ receipt and 125.8% for wait list mortality.

“Size mismatch between the donor and intended recipient and incorrect assessments of liver disease severity were more strongly associated with the observed sex disparity in wait list mortality than local supply of organs,” the investigators wrote.

Dr. Locke and colleagues noted that ongoing debates about geographic disparity hinge upon the assumption that the MELD score accurately measures disease severity, despite known shortcomings, including reliance upon serum creatinine level, which is influenced by muscle mass and therefore overestimates kidney function in women, and sex-based differences in size, which the MELD score does not incorporate whatsoever.

As such, the investigators suggested that addressing issues with the MELD score and organ size mismatch should be part of a more comprehensive approach to fixing sex-based disparities among candidates for liver transplant.

“Although geographic factors matter, examining geographic access alone may be insufficient,” they concluded.

James F. Markmann, MD, PhD, chief of the division of transplantation at Massachusetts General Hospital, Boston, who has previously published research in support of geographic redistribution, said in an interview that the study by Dr. Locke and colleagues “highlights a well-known problem in the liver transplant field.”

“The cause of this disparity is nicely illustrated by Dr. Locke’s work, which shows multiple contributing factors,” Dr. Markmann said.

While Dr. Markmann agreed with Dr. Locke and colleagues’ proposal that estimated glomerular filtration rate, instead of creatinine, could be used to more accurately measure renal function across sexes, he suggested that the disparities uncovered by their analysis are more likely driven by body size than sex.

“A more impactful factor and one obvious to those performing transplants is that on average the smaller body habitus of females makes more organs unsuitable due to size mismatch,” Dr. Markmann said. “In general, it is technically much less of a barrier to put a small liver into a large patient, than a large liver in a small patient. But, the same disparity in access almost certainly applies to small males; unfortunately, the authors did not examine this point. If allocation changes are envisioned to gain greater fairness in organ access, at least for the recipient size issue, it should be a size issue and not a sex issue.”

Dr. Markmann went on to explain that steps are currently being taken to make liver access more equitable.

“As of February 4th of this year, a broader sharing program for deceased donor livers was implemented,” he said. “This will make more organs available to those in greatest need. It will also potentially increase the number of liver offers to sick patients with a small body habitus and will hopefully reduce the excess morbidity and mortality they suffer.”

According to Willscott E. Naugler, MD and Susan L. Orloff, MD, of Oregon Health & Science University, Portland, novel clinical strategies need to be reinforced with a broader mindset in order to close the gap between men and women.

“A change in the MELD score is unlikely to fix this problem,” they wrote in an accompanying JAMA Surgery editorial, “but it is not hard to think of solutions; one could imagine, for example, allowing women of small stature to access pediatric livers while ramping up liver splits to increase contributions to the pediatric pool.”

Dr. Naugler and Dr. Orloff went on to suggest that barriers to equity may be culturally insidious.

“It is likely that the same unconscious biases that lead us to pay women surgeons less account for the lack of will to make these simple changes,” they wrote. “Not mentioned are multiple sociocultural elements that favor men over women in organ transplant. ... These realities cannot be fixed with changes to the MELD score, and we must be mindful not to let such notions distract from the essential hard work of creating long-lasting cultural changes that underpin a true path forward.”

The investigators disclosed relationships with Sanofi, Hansa Medical, Natera, and others.

SOURCE: Locke JE et al. JAMA Surg. 2020 May 20. doi: 10.1001/jamasurg.2020.1129.

Addressing local supply constraints may be insufficient to improve poorer outcomes among women who need a liver transplant, based on a large retrospective analysis.

Sex-based disparities in liver allocation were more strongly associated with liver size mismatch and MELD (Model for End-stage Liver Disease) score than geographic factors, reported lead author Jayme E. Locke, MD, of the University of Alabama at Birmingham, and colleagues.

“Currently, the transplant community is considering geographic redistribution ... to redefine local organ supply by replacing donor service areas with fixed concentric circles around donor hospitals,” the investigators wrote in JAMA Surgery. “However, newly proposed geographic models rely on the same metric for medical urgency, the MELD score, and offer no solution for candidates with small body stature who may appear at the top of the match run yet are routinely skipped secondary to discrepancies in donor-recipient size.”

To further investigate the driving forces behind sex-based disparities, the investigators conducted the first national study of its kind, involving 81,357 adults who were wait-listed for liver transplant. Primary outcomes included deceased donor liver transplant and wait list mortality. Using multivariate regression models and inverse odds ratio weighting, the investigators determined proportions of disparity shared across MELD score, candidate anthropometric and liver measurements, and geographic location.

Compared with men, women were 14.4% less likely to receive a transplant, and 8.6% more likely to die on the wait list.

The only geographic factor significantly associated with the increased disparity between female sex and wait list mortality was organ procurement organization, which was associated with a 22% increase. The disparity between rates of transplant receipt was not linked with any geographic factors.

In contrast, MELD score accounted for increases in disparity of 10.3% and 50.1% for organ receipt and wait list mortality, respectively. Candidate anthropometric and liver measurements played an even greater role, raising disparity by 49.0% for organ receipt and 125.8% for wait list mortality.

“Size mismatch between the donor and intended recipient and incorrect assessments of liver disease severity were more strongly associated with the observed sex disparity in wait list mortality than local supply of organs,” the investigators wrote.

Dr. Locke and colleagues noted that ongoing debates about geographic disparity hinge upon the assumption that the MELD score accurately measures disease severity, despite known shortcomings, including reliance upon serum creatinine level, which is influenced by muscle mass and therefore overestimates kidney function in women, and sex-based differences in size, which the MELD score does not incorporate whatsoever.

As such, the investigators suggested that addressing issues with the MELD score and organ size mismatch should be part of a more comprehensive approach to fixing sex-based disparities among candidates for liver transplant.

“Although geographic factors matter, examining geographic access alone may be insufficient,” they concluded.

James F. Markmann, MD, PhD, chief of the division of transplantation at Massachusetts General Hospital, Boston, who has previously published research in support of geographic redistribution, said in an interview that the study by Dr. Locke and colleagues “highlights a well-known problem in the liver transplant field.”

“The cause of this disparity is nicely illustrated by Dr. Locke’s work, which shows multiple contributing factors,” Dr. Markmann said.

While Dr. Markmann agreed with Dr. Locke and colleagues’ proposal that estimated glomerular filtration rate, instead of creatinine, could be used to more accurately measure renal function across sexes, he suggested that the disparities uncovered by their analysis are more likely driven by body size than sex.

“A more impactful factor and one obvious to those performing transplants is that on average the smaller body habitus of females makes more organs unsuitable due to size mismatch,” Dr. Markmann said. “In general, it is technically much less of a barrier to put a small liver into a large patient, than a large liver in a small patient. But, the same disparity in access almost certainly applies to small males; unfortunately, the authors did not examine this point. If allocation changes are envisioned to gain greater fairness in organ access, at least for the recipient size issue, it should be a size issue and not a sex issue.”

Dr. Markmann went on to explain that steps are currently being taken to make liver access more equitable.

“As of February 4th of this year, a broader sharing program for deceased donor livers was implemented,” he said. “This will make more organs available to those in greatest need. It will also potentially increase the number of liver offers to sick patients with a small body habitus and will hopefully reduce the excess morbidity and mortality they suffer.”

According to Willscott E. Naugler, MD and Susan L. Orloff, MD, of Oregon Health & Science University, Portland, novel clinical strategies need to be reinforced with a broader mindset in order to close the gap between men and women.

“A change in the MELD score is unlikely to fix this problem,” they wrote in an accompanying JAMA Surgery editorial, “but it is not hard to think of solutions; one could imagine, for example, allowing women of small stature to access pediatric livers while ramping up liver splits to increase contributions to the pediatric pool.”

Dr. Naugler and Dr. Orloff went on to suggest that barriers to equity may be culturally insidious.

“It is likely that the same unconscious biases that lead us to pay women surgeons less account for the lack of will to make these simple changes,” they wrote. “Not mentioned are multiple sociocultural elements that favor men over women in organ transplant. ... These realities cannot be fixed with changes to the MELD score, and we must be mindful not to let such notions distract from the essential hard work of creating long-lasting cultural changes that underpin a true path forward.”

The investigators disclosed relationships with Sanofi, Hansa Medical, Natera, and others.

SOURCE: Locke JE et al. JAMA Surg. 2020 May 20. doi: 10.1001/jamasurg.2020.1129.

For patients with BRCA-like triple-negative breast cancer (TNBC), adding veliparib to cisplatin chemotherapy may extend survival, based on results from the phase 3 SWOG S1416 trial.

All patients with BRCA-like TNBC had a significant improvement in progression-free survival (PFS) when they received veliparib plus cisplatin. Previously untreated patients with BRCA-like TNBC had a significant improvement in overall survival (OS) as well.

The results are a “very positive step towards expanding the role of PARP inhibitors beyond germline BRCA in breast cancer,” reported lead author Priyanka Sharma, MD, of the University of Kansas Medical Center in Kansas City, who presented the findings as part of the American Society of Clinical Oncology virtual scientific program.

According to Dr. Sharma, PARP inhibitors have demonstrated efficacy for certain patients with BRCA wild-type ovarian cancer, such as those with homologous recombination deficiency, which also occurs in approximately half of patients with BRCA wild-type TNBC. In TNBC, homologous recombination deficiency and other aberrations lead to a BRCA-like disease phenotype, which may respond to PARP inhibitors.

Dr. Sharma noted that previous attempts to use PARP inhibitors for BRCA wild-type TNBC have revealed obstacles, such as the inefficacy of PARP inhibitor monotherapy and dose-limiting myelosuppression when PARP inhibitors were added to chemotherapy. The issue of bone marrow toxicity may be mitigated by veliparib, which has minimal PARP-trapping activity, she explained.

“A phase 1 trial has demonstrated that adequate doses of cisplatin can be delivered safely in combination with the near-maximal single-agent dose of veliparib in patients with metastatic TNBC,” Dr. Sharma said.

She and her colleagues put this finding to the test in a phase 3 trial that enrolled 335 patients with metastatic and/or loco-regionally recurrent TNBC or BRCA-associated HER2-negative breast cancer. Patients could be previously untreated or have received one prior cytotoxic chemotherapy for metastatic disease.

Of the patients enrolled, 321 met eligibility criteria, 294 had germline BRCA testing, and 209 had BRCA-like assessment.

Patients were divided into the following groups: germline BRCA-associated disease (n = 37), BRCA-like disease (n = 99), non-BRCA-like disease (n = 110), and unclassified (n = 75).

In each group, patients were randomized in a 1:1 ratio to receive cisplatin (75 mg/m²on day 1) plus veliparib (300 mg twice daily on days 1-14) every 3 weeks, or cisplatin with placebo. The primary endpoint was PFS.

Results

Among patients with BRCA-like disease, there was a significant improvement in PFS and a trend toward improved OS when veliparib was added to cisplatin. The median PFS was 5.9 months with veliparib and 4.2 months with placebo (P = .006). The median OS was 14.0 months and 12.1 months, respectively (P = .067).

Among patients with previously untreated BRCA-like disease, there were significant improvements in both PFS and OS.

The median PFS in this group was 6.1 months with veliparib and 4.2 months with placebo (P = .008). The 12-month PFS rates were 23% and 3%, respectively.

The median OS in this group was 17.8 months with veliparib and 10.3 months with placebo (P = .048). The 24-month OS rates were 43% and 20%, respectively.

There were no survival benefits with veliparib among patients with unclassified disease, non-BRCA-like disease, or BRCA-associated disease.

Dr. Sharma noted that the lack of significant improvement in the BRCA-associated group was likely due to the small sample size. “FDA approval of PARP inhibitors for treatment of germline BRCA-associated metastatic breast cancer during the course of this trial impacted accrual to this group,” she said.

Veliparib was associated with a higher rate of grade 3-4 hematologic toxicities, including neutropenia (46% vs. 19%), leukopenia (27% vs. 7%), anemia (23% vs. 7%), and thrombocytopenia (19% vs. 3%).

Dr. Sharma said results from this trial should prompt further research. “The combination of veliparib plus cisplatin warrants further evaluation in larger randomized trials for patients with BRCA-like phenotype TNBC,” she said.

Invited discussant Catherine M. Kelly, MB BCh, of Mater Misericordiae University Hospital in Dublin, called the trial “an ambitious study” that has created a “valuable tissue bank” for future translational research. She agreed that more work is necessary.

“Further research is needed to identify the optimal homologous recombination deficiency biomarkers critical in the early treatment-naive and in the advanced treatment-exposed disease settings,” Dr. Kelly said.

SWOG S1416 was funded by the National Institutes of Health and AbbVie. Dr. Sharma disclosed relationships with AstraZeneca, Merck, Novartis, and other companies. Dr. Kelly reported affiliations with Pfizer, Novartis, Roche, and MSD Oncology.

SOURCE: Sharma et al. ASCO 2020, Abstract 1001.

For patients with BRCA-like triple-negative breast cancer (TNBC), adding veliparib to cisplatin chemotherapy may extend survival, based on results from the phase 3 SWOG S1416 trial.

All patients with BRCA-like TNBC had a significant improvement in progression-free survival (PFS) when they received veliparib plus cisplatin. Previously untreated patients with BRCA-like TNBC had a significant improvement in overall survival (OS) as well.

The results are a “very positive step towards expanding the role of PARP inhibitors beyond germline BRCA in breast cancer,” reported lead author Priyanka Sharma, MD, of the University of Kansas Medical Center in Kansas City, who presented the findings as part of the American Society of Clinical Oncology virtual scientific program.

According to Dr. Sharma, PARP inhibitors have demonstrated efficacy for certain patients with BRCA wild-type ovarian cancer, such as those with homologous recombination deficiency, which also occurs in approximately half of patients with BRCA wild-type TNBC. In TNBC, homologous recombination deficiency and other aberrations lead to a BRCA-like disease phenotype, which may respond to PARP inhibitors.

Dr. Sharma noted that previous attempts to use PARP inhibitors for BRCA wild-type TNBC have revealed obstacles, such as the inefficacy of PARP inhibitor monotherapy and dose-limiting myelosuppression when PARP inhibitors were added to chemotherapy. The issue of bone marrow toxicity may be mitigated by veliparib, which has minimal PARP-trapping activity, she explained.

“A phase 1 trial has demonstrated that adequate doses of cisplatin can be delivered safely in combination with the near-maximal single-agent dose of veliparib in patients with metastatic TNBC,” Dr. Sharma said.

She and her colleagues put this finding to the test in a phase 3 trial that enrolled 335 patients with metastatic and/or loco-regionally recurrent TNBC or BRCA-associated HER2-negative breast cancer. Patients could be previously untreated or have received one prior cytotoxic chemotherapy for metastatic disease.

Of the patients enrolled, 321 met eligibility criteria, 294 had germline BRCA testing, and 209 had BRCA-like assessment.

Patients were divided into the following groups: germline BRCA-associated disease (n = 37), BRCA-like disease (n = 99), non-BRCA-like disease (n = 110), and unclassified (n = 75).

In each group, patients were randomized in a 1:1 ratio to receive cisplatin (75 mg/m²on day 1) plus veliparib (300 mg twice daily on days 1-14) every 3 weeks, or cisplatin with placebo. The primary endpoint was PFS.

Results

Among patients with BRCA-like disease, there was a significant improvement in PFS and a trend toward improved OS when veliparib was added to cisplatin. The median PFS was 5.9 months with veliparib and 4.2 months with placebo (P = .006). The median OS was 14.0 months and 12.1 months, respectively (P = .067).

Among patients with previously untreated BRCA-like disease, there were significant improvements in both PFS and OS.

The median PFS in this group was 6.1 months with veliparib and 4.2 months with placebo (P = .008). The 12-month PFS rates were 23% and 3%, respectively.

The median OS in this group was 17.8 months with veliparib and 10.3 months with placebo (P = .048). The 24-month OS rates were 43% and 20%, respectively.

There were no survival benefits with veliparib among patients with unclassified disease, non-BRCA-like disease, or BRCA-associated disease.

Dr. Sharma noted that the lack of significant improvement in the BRCA-associated group was likely due to the small sample size. “FDA approval of PARP inhibitors for treatment of germline BRCA-associated metastatic breast cancer during the course of this trial impacted accrual to this group,” she said.

Veliparib was associated with a higher rate of grade 3-4 hematologic toxicities, including neutropenia (46% vs. 19%), leukopenia (27% vs. 7%), anemia (23% vs. 7%), and thrombocytopenia (19% vs. 3%).

Dr. Sharma said results from this trial should prompt further research. “The combination of veliparib plus cisplatin warrants further evaluation in larger randomized trials for patients with BRCA-like phenotype TNBC,” she said.

Invited discussant Catherine M. Kelly, MB BCh, of Mater Misericordiae University Hospital in Dublin, called the trial “an ambitious study” that has created a “valuable tissue bank” for future translational research. She agreed that more work is necessary.

“Further research is needed to identify the optimal homologous recombination deficiency biomarkers critical in the early treatment-naive and in the advanced treatment-exposed disease settings,” Dr. Kelly said.

SWOG S1416 was funded by the National Institutes of Health and AbbVie. Dr. Sharma disclosed relationships with AstraZeneca, Merck, Novartis, and other companies. Dr. Kelly reported affiliations with Pfizer, Novartis, Roche, and MSD Oncology.

SOURCE: Sharma et al. ASCO 2020, Abstract 1001.

For patients with BRCA-like triple-negative breast cancer (TNBC), adding veliparib to cisplatin chemotherapy may extend survival, based on results from the phase 3 SWOG S1416 trial.

All patients with BRCA-like TNBC had a significant improvement in progression-free survival (PFS) when they received veliparib plus cisplatin. Previously untreated patients with BRCA-like TNBC had a significant improvement in overall survival (OS) as well.

The results are a “very positive step towards expanding the role of PARP inhibitors beyond germline BRCA in breast cancer,” reported lead author Priyanka Sharma, MD, of the University of Kansas Medical Center in Kansas City, who presented the findings as part of the American Society of Clinical Oncology virtual scientific program.

According to Dr. Sharma, PARP inhibitors have demonstrated efficacy for certain patients with BRCA wild-type ovarian cancer, such as those with homologous recombination deficiency, which also occurs in approximately half of patients with BRCA wild-type TNBC. In TNBC, homologous recombination deficiency and other aberrations lead to a BRCA-like disease phenotype, which may respond to PARP inhibitors.

Dr. Sharma noted that previous attempts to use PARP inhibitors for BRCA wild-type TNBC have revealed obstacles, such as the inefficacy of PARP inhibitor monotherapy and dose-limiting myelosuppression when PARP inhibitors were added to chemotherapy. The issue of bone marrow toxicity may be mitigated by veliparib, which has minimal PARP-trapping activity, she explained.

“A phase 1 trial has demonstrated that adequate doses of cisplatin can be delivered safely in combination with the near-maximal single-agent dose of veliparib in patients with metastatic TNBC,” Dr. Sharma said.

She and her colleagues put this finding to the test in a phase 3 trial that enrolled 335 patients with metastatic and/or loco-regionally recurrent TNBC or BRCA-associated HER2-negative breast cancer. Patients could be previously untreated or have received one prior cytotoxic chemotherapy for metastatic disease.

Of the patients enrolled, 321 met eligibility criteria, 294 had germline BRCA testing, and 209 had BRCA-like assessment.

Patients were divided into the following groups: germline BRCA-associated disease (n = 37), BRCA-like disease (n = 99), non-BRCA-like disease (n = 110), and unclassified (n = 75).

In each group, patients were randomized in a 1:1 ratio to receive cisplatin (75 mg/m²on day 1) plus veliparib (300 mg twice daily on days 1-14) every 3 weeks, or cisplatin with placebo. The primary endpoint was PFS.

Results

Among patients with BRCA-like disease, there was a significant improvement in PFS and a trend toward improved OS when veliparib was added to cisplatin. The median PFS was 5.9 months with veliparib and 4.2 months with placebo (P = .006). The median OS was 14.0 months and 12.1 months, respectively (P = .067).

Among patients with previously untreated BRCA-like disease, there were significant improvements in both PFS and OS.

The median PFS in this group was 6.1 months with veliparib and 4.2 months with placebo (P = .008). The 12-month PFS rates were 23% and 3%, respectively.

The median OS in this group was 17.8 months with veliparib and 10.3 months with placebo (P = .048). The 24-month OS rates were 43% and 20%, respectively.

There were no survival benefits with veliparib among patients with unclassified disease, non-BRCA-like disease, or BRCA-associated disease.

Dr. Sharma noted that the lack of significant improvement in the BRCA-associated group was likely due to the small sample size. “FDA approval of PARP inhibitors for treatment of germline BRCA-associated metastatic breast cancer during the course of this trial impacted accrual to this group,” she said.

Veliparib was associated with a higher rate of grade 3-4 hematologic toxicities, including neutropenia (46% vs. 19%), leukopenia (27% vs. 7%), anemia (23% vs. 7%), and thrombocytopenia (19% vs. 3%).

Dr. Sharma said results from this trial should prompt further research. “The combination of veliparib plus cisplatin warrants further evaluation in larger randomized trials for patients with BRCA-like phenotype TNBC,” she said.

Invited discussant Catherine M. Kelly, MB BCh, of Mater Misericordiae University Hospital in Dublin, called the trial “an ambitious study” that has created a “valuable tissue bank” for future translational research. She agreed that more work is necessary.

“Further research is needed to identify the optimal homologous recombination deficiency biomarkers critical in the early treatment-naive and in the advanced treatment-exposed disease settings,” Dr. Kelly said.

SWOG S1416 was funded by the National Institutes of Health and AbbVie. Dr. Sharma disclosed relationships with AstraZeneca, Merck, Novartis, and other companies. Dr. Kelly reported affiliations with Pfizer, Novartis, Roche, and MSD Oncology.

SOURCE: Sharma et al. ASCO 2020, Abstract 1001.

For patients with triple-negative breast cancer (TNBC), 1 year of capecitabine treatment after standard therapy may lead to significantly better disease-free survival (DFS), but not overall survival (OS), according to results of a phase 3 trial.

Patients who received metronomic capecitabine maintenance had significantly higher rates of 5-year DFS and distant DFS, but not OS, when compared with patients who did not receive capecitabine, reported Xi Wang, PhD, of Sun Yat-sen University Cancer Center in Guangzhou, China, who presented the findings as part of the American Society of Clinical Oncology virtual scientific program.

“TNBC has the worst outcomes among all subtypes of breast cancer,” Dr. Wang said. “Effective strategies to reduce risk of relapse are a critical clinical need.”

He went on to describe capecitabine as a “potential ideal drug for metronomic administration,” particularly among patients with high risk of distant metastasis.

With that in mind, Dr. Wang and colleagues tested metronomic capecitabine maintenance in the phase 3 SYSUCC-001 trial. The trial included 434 patients with invasive ductal carcinoma. They had undergone standard therapy, which included surgery, neoadjuvant/adjuvant chemotherapy, and radiation therapy.

Patients were randomized to receive capecitabine at 650 mg/m² twice daily for 1 year (n = 221) or undergo observation (n = 213). The primary endpoint was DFS, while secondary endpoints included safety, distant DFS, and OS.

According to Dr. Wang, the two patient groups were “well balanced,” with similar baseline characteristics. Most patients underwent adjuvant chemotherapy (93%), had histological grade 3 tumors (71%-74%), had a Ki-67 index of at least 30% (73%-80%), had negative lymph node status (61%-62%), had a tumor size of 2.1-5 cm (55%-58%), and/or pathologic stage II disease (54%-55%).
 

Survival and safety

At a median follow-up of 56.5 months, the median 5-year DFS rate was 83% in the capecitabine group, compared with 73% in the observation group (P = .027). Similarly, capecitabine use correlated with a significantly better rate of distant DFS (85% vs. 76%; P = .016).

Although the capecitabine group demonstrated a slight trend toward improved OS at 5 years, this finding was not statistically significant (86% vs. 81%; P = .203).

Capecitabine was generally well tolerated, with 91% of patients completing 1 year of therapy, and 75% completing therapy at the full dose.

Almost half of patients in the capecitabine group experienced hand-foot syndrome (45%), and one in four developed leukopenia (24%). Less common adverse events included hyperbilirubinemia (13%), gastrointestinal pain (7%), and elevated serum transaminases (5%). No unexpected serious adverse events occurred.
 

Effects on practice

Amy Tiersten, MD, of the Icahn School of Medicine at Mount Sinai in New York, suggested these findings may lead to broader use of capecitabine among patients with TNBC.

“[This is a] very exciting study showing an impressive disease-free survival benefit in the adjuvant setting for capecitabine in patients with early stage TNBC,” Dr. Tiersten said. “Presently, we only have positive data for capecitabine in patients with residual disease after neoadjuvant therapy, but this current study now suggests that this benefit could extend to all comers.”

Dr. Tiersten advised that the medical community stay tuned, since longer-term data may provide a clearer picture of survival benefit.

“It will be interesting to see if there is an impact on overall survival with further follow-up,” she said.

According to invited discussant Naamit Kurshan Gerber, MD, of New York University, the results support previous findings from the CREATE-X trial, along with meta-analyses that have shown a “preferential benefit” of capecitabine when used to treat TNBC, compared with estrogen receptor–positive disease.

Still, Dr. Gerber noted that, for most patients, the findings from the SYSUCC-001 trial are unlikely to influence clinical decision-making since most patients with TNBC receive neoadjuvant chemotherapy followed by treatment based on pathologic response. However, she also suggested that, after peer review, the findings could influence treatment for a select few.

“For the small population of patients who receive adjuvant chemotherapy for higher-stage TNBC and who would have met eligibility criteria, this approach may be considered,” Dr. Gerber said.

The study was funded by the Sun Yat-sen University Clinical Research 5010 Program. The investigators disclosed no conflicts of interest. Dr. Gerber reported a relationship with OncLive. Dr. Tiersten reported no relevant disclosures.

SOURCE: Wang X et al. ASCO 2020, Abstract 507.

For patients with triple-negative breast cancer (TNBC), 1 year of capecitabine treatment after standard therapy may lead to significantly better disease-free survival (DFS), but not overall survival (OS), according to results of a phase 3 trial.

Patients who received metronomic capecitabine maintenance had significantly higher rates of 5-year DFS and distant DFS, but not OS, when compared with patients who did not receive capecitabine, reported Xi Wang, PhD, of Sun Yat-sen University Cancer Center in Guangzhou, China, who presented the findings as part of the American Society of Clinical Oncology virtual scientific program.

“TNBC has the worst outcomes among all subtypes of breast cancer,” Dr. Wang said. “Effective strategies to reduce risk of relapse are a critical clinical need.”

He went on to describe capecitabine as a “potential ideal drug for metronomic administration,” particularly among patients with high risk of distant metastasis.

With that in mind, Dr. Wang and colleagues tested metronomic capecitabine maintenance in the phase 3 SYSUCC-001 trial. The trial included 434 patients with invasive ductal carcinoma. They had undergone standard therapy, which included surgery, neoadjuvant/adjuvant chemotherapy, and radiation therapy.

Patients were randomized to receive capecitabine at 650 mg/m² twice daily for 1 year (n = 221) or undergo observation (n = 213). The primary endpoint was DFS, while secondary endpoints included safety, distant DFS, and OS.

According to Dr. Wang, the two patient groups were “well balanced,” with similar baseline characteristics. Most patients underwent adjuvant chemotherapy (93%), had histological grade 3 tumors (71%-74%), had a Ki-67 index of at least 30% (73%-80%), had negative lymph node status (61%-62%), had a tumor size of 2.1-5 cm (55%-58%), and/or pathologic stage II disease (54%-55%).
 

Survival and safety

At a median follow-up of 56.5 months, the median 5-year DFS rate was 83% in the capecitabine group, compared with 73% in the observation group (P = .027). Similarly, capecitabine use correlated with a significantly better rate of distant DFS (85% vs. 76%; P = .016).

Although the capecitabine group demonstrated a slight trend toward improved OS at 5 years, this finding was not statistically significant (86% vs. 81%; P = .203).

Capecitabine was generally well tolerated, with 91% of patients completing 1 year of therapy, and 75% completing therapy at the full dose.

Almost half of patients in the capecitabine group experienced hand-foot syndrome (45%), and one in four developed leukopenia (24%). Less common adverse events included hyperbilirubinemia (13%), gastrointestinal pain (7%), and elevated serum transaminases (5%). No unexpected serious adverse events occurred.
 

Effects on practice

Amy Tiersten, MD, of the Icahn School of Medicine at Mount Sinai in New York, suggested these findings may lead to broader use of capecitabine among patients with TNBC.

“[This is a] very exciting study showing an impressive disease-free survival benefit in the adjuvant setting for capecitabine in patients with early stage TNBC,” Dr. Tiersten said. “Presently, we only have positive data for capecitabine in patients with residual disease after neoadjuvant therapy, but this current study now suggests that this benefit could extend to all comers.”

Dr. Tiersten advised that the medical community stay tuned, since longer-term data may provide a clearer picture of survival benefit.

“It will be interesting to see if there is an impact on overall survival with further follow-up,” she said.

According to invited discussant Naamit Kurshan Gerber, MD, of New York University, the results support previous findings from the CREATE-X trial, along with meta-analyses that have shown a “preferential benefit” of capecitabine when used to treat TNBC, compared with estrogen receptor–positive disease.

Still, Dr. Gerber noted that, for most patients, the findings from the SYSUCC-001 trial are unlikely to influence clinical decision-making since most patients with TNBC receive neoadjuvant chemotherapy followed by treatment based on pathologic response. However, she also suggested that, after peer review, the findings could influence treatment for a select few.

“For the small population of patients who receive adjuvant chemotherapy for higher-stage TNBC and who would have met eligibility criteria, this approach may be considered,” Dr. Gerber said.

The study was funded by the Sun Yat-sen University Clinical Research 5010 Program. The investigators disclosed no conflicts of interest. Dr. Gerber reported a relationship with OncLive. Dr. Tiersten reported no relevant disclosures.

SOURCE: Wang X et al. ASCO 2020, Abstract 507.

For patients with triple-negative breast cancer (TNBC), 1 year of capecitabine treatment after standard therapy may lead to significantly better disease-free survival (DFS), but not overall survival (OS), according to results of a phase 3 trial.

Patients who received metronomic capecitabine maintenance had significantly higher rates of 5-year DFS and distant DFS, but not OS, when compared with patients who did not receive capecitabine, reported Xi Wang, PhD, of Sun Yat-sen University Cancer Center in Guangzhou, China, who presented the findings as part of the American Society of Clinical Oncology virtual scientific program.

“TNBC has the worst outcomes among all subtypes of breast cancer,” Dr. Wang said. “Effective strategies to reduce risk of relapse are a critical clinical need.”

He went on to describe capecitabine as a “potential ideal drug for metronomic administration,” particularly among patients with high risk of distant metastasis.

With that in mind, Dr. Wang and colleagues tested metronomic capecitabine maintenance in the phase 3 SYSUCC-001 trial. The trial included 434 patients with invasive ductal carcinoma. They had undergone standard therapy, which included surgery, neoadjuvant/adjuvant chemotherapy, and radiation therapy.

Patients were randomized to receive capecitabine at 650 mg/m² twice daily for 1 year (n = 221) or undergo observation (n = 213). The primary endpoint was DFS, while secondary endpoints included safety, distant DFS, and OS.

According to Dr. Wang, the two patient groups were “well balanced,” with similar baseline characteristics. Most patients underwent adjuvant chemotherapy (93%), had histological grade 3 tumors (71%-74%), had a Ki-67 index of at least 30% (73%-80%), had negative lymph node status (61%-62%), had a tumor size of 2.1-5 cm (55%-58%), and/or pathologic stage II disease (54%-55%).
 

Survival and safety

At a median follow-up of 56.5 months, the median 5-year DFS rate was 83% in the capecitabine group, compared with 73% in the observation group (P = .027). Similarly, capecitabine use correlated with a significantly better rate of distant DFS (85% vs. 76%; P = .016).

Although the capecitabine group demonstrated a slight trend toward improved OS at 5 years, this finding was not statistically significant (86% vs. 81%; P = .203).

Capecitabine was generally well tolerated, with 91% of patients completing 1 year of therapy, and 75% completing therapy at the full dose.

Almost half of patients in the capecitabine group experienced hand-foot syndrome (45%), and one in four developed leukopenia (24%). Less common adverse events included hyperbilirubinemia (13%), gastrointestinal pain (7%), and elevated serum transaminases (5%). No unexpected serious adverse events occurred.
 

Effects on practice

Amy Tiersten, MD, of the Icahn School of Medicine at Mount Sinai in New York, suggested these findings may lead to broader use of capecitabine among patients with TNBC.

“[This is a] very exciting study showing an impressive disease-free survival benefit in the adjuvant setting for capecitabine in patients with early stage TNBC,” Dr. Tiersten said. “Presently, we only have positive data for capecitabine in patients with residual disease after neoadjuvant therapy, but this current study now suggests that this benefit could extend to all comers.”

Dr. Tiersten advised that the medical community stay tuned, since longer-term data may provide a clearer picture of survival benefit.

“It will be interesting to see if there is an impact on overall survival with further follow-up,” she said.

According to invited discussant Naamit Kurshan Gerber, MD, of New York University, the results support previous findings from the CREATE-X trial, along with meta-analyses that have shown a “preferential benefit” of capecitabine when used to treat TNBC, compared with estrogen receptor–positive disease.

Still, Dr. Gerber noted that, for most patients, the findings from the SYSUCC-001 trial are unlikely to influence clinical decision-making since most patients with TNBC receive neoadjuvant chemotherapy followed by treatment based on pathologic response. However, she also suggested that, after peer review, the findings could influence treatment for a select few.

“For the small population of patients who receive adjuvant chemotherapy for higher-stage TNBC and who would have met eligibility criteria, this approach may be considered,” Dr. Gerber said.

The study was funded by the Sun Yat-sen University Clinical Research 5010 Program. The investigators disclosed no conflicts of interest. Dr. Gerber reported a relationship with OncLive. Dr. Tiersten reported no relevant disclosures.

SOURCE: Wang X et al. ASCO 2020, Abstract 507.

For patients with inflammatory bowel disease (IBD) who develop coronavirus disease of 2019 (COVID-19), corticosteroid use may significantly increase risk of severe disease, according to data from more than 500 patients.

Use of sulfasalazine or 5-aminosalicylates (5-ASAs) also increased risk of severe COVID-19, albeit to a lesser degree, reported co-lead authors Erica J. Brenner, MD, of University of North Carolina Children’s Hospital, Chapel Hill, and Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues.

In contrast, tumor necrosis factor (TNF) blockers were not an independent risk factor for severe COVID-19.

“As TNF antagonists are the most commonly prescribed biologic therapy for patients with IBD, these initial findings should be reassuring to the large number of patients receiving TNF antagonist therapy and support their continued use during this current pandemic,” the investigators wrote in Gastroenterology.

These conclusions were drawn from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) database, a large registry actively collecting data from clinicians around the world.

In the present analysis, which involved 525 patients from 33 countries, the investigators searched for independent risk factors for severe COVID-19. Various factors were tested through multivariable regression, including age, comorbidities, usage of specific medications, and more.

The primary outcome was defined by a composite of hospitalization, ventilator use, or death, while secondary outcomes included a composite of hospitalization or death, as well as death alone.

The analysis revealed that patients receiving corticosteroids had an adjusted odds ratio of 6.87 (95% confidence interval, 2.30-20.51) for severe COVID-19, with increased risks also detected for both secondary outcomes. In contrast, TNF antagonist use was not significantly associated with the primary outcome; in fact, a possible protective effect was detected for hospitalization or death (aOR, 0.60; 95% CI, 0.38-0.96).

The investigators noted that the above findings aligned with extensive literature concerning infectious complications with corticosteroid use and “more recent commentary” surrounding TNF antagonists. Similarly, increased age and the presence of at least two comorbidities were each independently associated with increased risk of severe COVID-19, both of which are correlations that have been previously described.

But the threefold increased risk of severe COVID-19 associated with use of sulfasalazine or 5-ASAs (aOR, 3.14; 95% CI, 1.28-7.71) was a “surprising” finding, the investigators noted.

“In a direct comparison, we observed that 5-ASA/sulfasalazine–treated patients fared worse than those treated with TNF inhibitors,” the investigators wrote. “Although we cannot exclude unmeasured confounding, further exploration of biological mechanisms is warranted.”

David T. Rubin, MD, AGAF, of the University of Chicago agreed that the finding deserves further investigation, particularly since sulfasalazine and 5-ASAs represent the second most commonly prescribed medication class for IBD.

“The risk with 5-ASAs is of interest but not well explained by what we know about the safety or the mechanism of these therapies,” Dr. Rubin said. “Clearly, more work is needed.”

The risks associated with corticosteroids were particularly concerning, Dr. Rubin said, because 10%-20% of patients with IBD may be taking corticosteroids at any given time.

“Steroids are still the number one prescribed therapy for Crohn’s and colitis,” he said.

Still, Dr. Rubin advised against abrupt changes to drug regimens, especially if they are effectively controlling IBD.

“Patients should stay on their existing therapies and stay in remission,” Dr. Rubin said. “If you stop your therapies … you are more likely to relapse. When you relapse, you’re more likely to need steroids as a rescue therapy … or end up in the hospital, and those are not places we want you to be.”

Despite the risks associated with steroids and sulfasalazine/5-ASAs, Dr. Rubin had an optimistic take on the study, calling the findings “very reassuring” because they support continued usage of TNF inhibitors and other biologic agents during the pandemic. He also noted that the SECURE-IBD registry, which he has contributed to, represents “an extraordinary effort” from around the world.

“[This is] an unprecedented collaboration across a scale and timeframe that has really never been seen before in our field, and I would hazard a guess that it’s probably never been seen in most other fields right now,” he said.

Clinicians seeking more information about managing patients with IBD during the COVID-19 pandemic can find guidance in the recent AGA practice update, of which Dr. Rubin was the lead author. Clinicians who would like to contribute to the SECURE-IBD registry may do so at covidibd.org. The registry now includes more than 1,000 patients.

The study was funded by Clinical and Translational Science Award grants through Dr. Ungaro. The investigators disclosed relationships with Takeda, Janssen, Pfizer, and others. Dr. Rubin disclosed relationships with Gilead, Eli Lilly, Shire, and others.

Check out the AGA COVID-19 Resource Library for new clinical guidance, education, research and physician resources, including recent guidance on how to treat patients with IBD during the pandemic, at www.gastro.org/covid.

SOURCE: Brenner EJ et al. Gastroenterology. 2020 May 18. doi: 10.1053/j.gastro.2020.05.032.

For patients with inflammatory bowel disease (IBD) who develop coronavirus disease of 2019 (COVID-19), corticosteroid use may significantly increase risk of severe disease, according to data from more than 500 patients.

Use of sulfasalazine or 5-aminosalicylates (5-ASAs) also increased risk of severe COVID-19, albeit to a lesser degree, reported co-lead authors Erica J. Brenner, MD, of University of North Carolina Children’s Hospital, Chapel Hill, and Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues.

In contrast, tumor necrosis factor (TNF) blockers were not an independent risk factor for severe COVID-19.

“As TNF antagonists are the most commonly prescribed biologic therapy for patients with IBD, these initial findings should be reassuring to the large number of patients receiving TNF antagonist therapy and support their continued use during this current pandemic,” the investigators wrote in Gastroenterology.

These conclusions were drawn from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) database, a large registry actively collecting data from clinicians around the world.

In the present analysis, which involved 525 patients from 33 countries, the investigators searched for independent risk factors for severe COVID-19. Various factors were tested through multivariable regression, including age, comorbidities, usage of specific medications, and more.

The primary outcome was defined by a composite of hospitalization, ventilator use, or death, while secondary outcomes included a composite of hospitalization or death, as well as death alone.

The analysis revealed that patients receiving corticosteroids had an adjusted odds ratio of 6.87 (95% confidence interval, 2.30-20.51) for severe COVID-19, with increased risks also detected for both secondary outcomes. In contrast, TNF antagonist use was not significantly associated with the primary outcome; in fact, a possible protective effect was detected for hospitalization or death (aOR, 0.60; 95% CI, 0.38-0.96).

The investigators noted that the above findings aligned with extensive literature concerning infectious complications with corticosteroid use and “more recent commentary” surrounding TNF antagonists. Similarly, increased age and the presence of at least two comorbidities were each independently associated with increased risk of severe COVID-19, both of which are correlations that have been previously described.

But the threefold increased risk of severe COVID-19 associated with use of sulfasalazine or 5-ASAs (aOR, 3.14; 95% CI, 1.28-7.71) was a “surprising” finding, the investigators noted.

“In a direct comparison, we observed that 5-ASA/sulfasalazine–treated patients fared worse than those treated with TNF inhibitors,” the investigators wrote. “Although we cannot exclude unmeasured confounding, further exploration of biological mechanisms is warranted.”

David T. Rubin, MD, AGAF, of the University of Chicago agreed that the finding deserves further investigation, particularly since sulfasalazine and 5-ASAs represent the second most commonly prescribed medication class for IBD.

“The risk with 5-ASAs is of interest but not well explained by what we know about the safety or the mechanism of these therapies,” Dr. Rubin said. “Clearly, more work is needed.”

The risks associated with corticosteroids were particularly concerning, Dr. Rubin said, because 10%-20% of patients with IBD may be taking corticosteroids at any given time.

“Steroids are still the number one prescribed therapy for Crohn’s and colitis,” he said.

Still, Dr. Rubin advised against abrupt changes to drug regimens, especially if they are effectively controlling IBD.

“Patients should stay on their existing therapies and stay in remission,” Dr. Rubin said. “If you stop your therapies … you are more likely to relapse. When you relapse, you’re more likely to need steroids as a rescue therapy … or end up in the hospital, and those are not places we want you to be.”

Despite the risks associated with steroids and sulfasalazine/5-ASAs, Dr. Rubin had an optimistic take on the study, calling the findings “very reassuring” because they support continued usage of TNF inhibitors and other biologic agents during the pandemic. He also noted that the SECURE-IBD registry, which he has contributed to, represents “an extraordinary effort” from around the world.

“[This is] an unprecedented collaboration across a scale and timeframe that has really never been seen before in our field, and I would hazard a guess that it’s probably never been seen in most other fields right now,” he said.

Clinicians seeking more information about managing patients with IBD during the COVID-19 pandemic can find guidance in the recent AGA practice update, of which Dr. Rubin was the lead author. Clinicians who would like to contribute to the SECURE-IBD registry may do so at covidibd.org. The registry now includes more than 1,000 patients.

The study was funded by Clinical and Translational Science Award grants through Dr. Ungaro. The investigators disclosed relationships with Takeda, Janssen, Pfizer, and others. Dr. Rubin disclosed relationships with Gilead, Eli Lilly, Shire, and others.

Check out the AGA COVID-19 Resource Library for new clinical guidance, education, research and physician resources, including recent guidance on how to treat patients with IBD during the pandemic, at www.gastro.org/covid.

SOURCE: Brenner EJ et al. Gastroenterology. 2020 May 18. doi: 10.1053/j.gastro.2020.05.032.

For patients with inflammatory bowel disease (IBD) who develop coronavirus disease of 2019 (COVID-19), corticosteroid use may significantly increase risk of severe disease, according to data from more than 500 patients.

Use of sulfasalazine or 5-aminosalicylates (5-ASAs) also increased risk of severe COVID-19, albeit to a lesser degree, reported co-lead authors Erica J. Brenner, MD, of University of North Carolina Children’s Hospital, Chapel Hill, and Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues.

In contrast, tumor necrosis factor (TNF) blockers were not an independent risk factor for severe COVID-19.

“As TNF antagonists are the most commonly prescribed biologic therapy for patients with IBD, these initial findings should be reassuring to the large number of patients receiving TNF antagonist therapy and support their continued use during this current pandemic,” the investigators wrote in Gastroenterology.

These conclusions were drawn from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) database, a large registry actively collecting data from clinicians around the world.

In the present analysis, which involved 525 patients from 33 countries, the investigators searched for independent risk factors for severe COVID-19. Various factors were tested through multivariable regression, including age, comorbidities, usage of specific medications, and more.

The primary outcome was defined by a composite of hospitalization, ventilator use, or death, while secondary outcomes included a composite of hospitalization or death, as well as death alone.

The analysis revealed that patients receiving corticosteroids had an adjusted odds ratio of 6.87 (95% confidence interval, 2.30-20.51) for severe COVID-19, with increased risks also detected for both secondary outcomes. In contrast, TNF antagonist use was not significantly associated with the primary outcome; in fact, a possible protective effect was detected for hospitalization or death (aOR, 0.60; 95% CI, 0.38-0.96).

The investigators noted that the above findings aligned with extensive literature concerning infectious complications with corticosteroid use and “more recent commentary” surrounding TNF antagonists. Similarly, increased age and the presence of at least two comorbidities were each independently associated with increased risk of severe COVID-19, both of which are correlations that have been previously described.

But the threefold increased risk of severe COVID-19 associated with use of sulfasalazine or 5-ASAs (aOR, 3.14; 95% CI, 1.28-7.71) was a “surprising” finding, the investigators noted.

“In a direct comparison, we observed that 5-ASA/sulfasalazine–treated patients fared worse than those treated with TNF inhibitors,” the investigators wrote. “Although we cannot exclude unmeasured confounding, further exploration of biological mechanisms is warranted.”

David T. Rubin, MD, AGAF, of the University of Chicago agreed that the finding deserves further investigation, particularly since sulfasalazine and 5-ASAs represent the second most commonly prescribed medication class for IBD.

“The risk with 5-ASAs is of interest but not well explained by what we know about the safety or the mechanism of these therapies,” Dr. Rubin said. “Clearly, more work is needed.”

The risks associated with corticosteroids were particularly concerning, Dr. Rubin said, because 10%-20% of patients with IBD may be taking corticosteroids at any given time.

“Steroids are still the number one prescribed therapy for Crohn’s and colitis,” he said.

Still, Dr. Rubin advised against abrupt changes to drug regimens, especially if they are effectively controlling IBD.

“Patients should stay on their existing therapies and stay in remission,” Dr. Rubin said. “If you stop your therapies … you are more likely to relapse. When you relapse, you’re more likely to need steroids as a rescue therapy … or end up in the hospital, and those are not places we want you to be.”

Despite the risks associated with steroids and sulfasalazine/5-ASAs, Dr. Rubin had an optimistic take on the study, calling the findings “very reassuring” because they support continued usage of TNF inhibitors and other biologic agents during the pandemic. He also noted that the SECURE-IBD registry, which he has contributed to, represents “an extraordinary effort” from around the world.

“[This is] an unprecedented collaboration across a scale and timeframe that has really never been seen before in our field, and I would hazard a guess that it’s probably never been seen in most other fields right now,” he said.

Clinicians seeking more information about managing patients with IBD during the COVID-19 pandemic can find guidance in the recent AGA practice update, of which Dr. Rubin was the lead author. Clinicians who would like to contribute to the SECURE-IBD registry may do so at covidibd.org. The registry now includes more than 1,000 patients.

The study was funded by Clinical and Translational Science Award grants through Dr. Ungaro. The investigators disclosed relationships with Takeda, Janssen, Pfizer, and others. Dr. Rubin disclosed relationships with Gilead, Eli Lilly, Shire, and others.

Check out the AGA COVID-19 Resource Library for new clinical guidance, education, research and physician resources, including recent guidance on how to treat patients with IBD during the pandemic, at www.gastro.org/covid.

SOURCE: Brenner EJ et al. Gastroenterology. 2020 May 18. doi: 10.1053/j.gastro.2020.05.032.

For patients with inflammatory bowel disease (IBD) who develop coronavirus disease of 2019 (COVID-19), corticosteroid use may significantly increase risk of severe disease, according to data from more than 500 patients.

Use of sulfasalazine or 5-aminosalicylates (5-ASAs) also increased risk of severe COVID-19, albeit to a lesser degree, reported co-lead authors Erica J. Brenner, MD, of University of North Carolina Children’s Hospital, Chapel Hill, and Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues.

In contrast, tumor necrosis factor (TNF) blockers were not an independent risk factor for severe COVID-19.

“As TNF antagonists are the most commonly prescribed biologic therapy for patients with IBD, these initial findings should be reassuring to the large number of patients receiving TNF antagonist therapy and support their continued use during this current pandemic,” the investigators wrote in Gastroenterology.

These conclusions were drawn from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) database, a large registry actively collecting data from clinicians around the world.

In the present analysis, which involved 525 patients from 33 countries, the investigators searched for independent risk factors for severe COVID-19. Various factors were tested through multivariable regression, including age, comorbidities, usage of specific medications, and more.

The primary outcome was defined by a composite of hospitalization, ventilator use, or death, while secondary outcomes included a composite of hospitalization or death, as well as death alone.

The analysis revealed that patients receiving corticosteroids had an adjusted odds ratio of 6.87 (95% confidence interval, 2.30-20.51) for severe COVID-19, with increased risks also detected for both secondary outcomes. In contrast, TNF antagonist use was not significantly associated with the primary outcome; in fact, a possible protective effect was detected for hospitalization or death (aOR, 0.60; 95% CI, 0.38-0.96).

The investigators noted that the above findings aligned with extensive literature concerning infectious complications with corticosteroid use and “more recent commentary” surrounding TNF antagonists. Similarly, increased age and the presence of at least two comorbidities were each independently associated with increased risk of severe COVID-19, both of which are correlations that have been previously described.

But the threefold increased risk of severe COVID-19 associated with use of sulfasalazine or 5-ASAs (aOR, 3.14; 95% CI, 1.28-7.71) was a “surprising” finding, the investigators noted.

“In a direct comparison, we observed that 5-ASA/sulfasalazine–treated patients fared worse than those treated with TNF inhibitors,” the investigators wrote. “Although we cannot exclude unmeasured confounding, further exploration of biological mechanisms is warranted.”

David T. Rubin, MD, of the University of Chicago agreed that the finding deserves further investigation, particularly since sulfasalazine and 5-ASAs represent the second most commonly prescribed medication class for IBD.

“The risk with 5-ASAs is of interest but not well explained by what we know about the safety or the mechanism of these therapies,” Dr. Rubin said. “Clearly, more work is needed.”

The risks associated with corticosteroids were particularly concerning, Dr. Rubin said, because 10%-20% of patients with IBD may be taking corticosteroids at any given time.

“Steroids are still the number one prescribed therapy for Crohn’s and colitis,” he said.

Still, Dr. Rubin advised against abrupt changes to drug regimens, especially if they are effectively controlling IBD.

“Patients should stay on their existing therapies and stay in remission,” Dr. Rubin said. “If you stop your therapies … you are more likely to relapse. When you relapse, you’re more likely to need steroids as a rescue therapy … or end up in the hospital, and those are not places we want you to be.”

Despite the risks associated with steroids and sulfasalazine/5-ASAs, Dr. Rubin had an optimistic take on the study, calling the findings “very reassuring” because they support continued usage of TNF inhibitors and other biologic agents during the pandemic. He also noted that the SECURE-IBD registry, which he has contributed to, represents “an extraordinary effort” from around the world.

“[This is] an unprecedented collaboration across a scale and timeframe that has really never been seen before in our field, and I would hazard a guess that it’s probably never been seen in most other fields right now,” he said.

Clinicians seeking more information about managing patients with IBD during the COVID-19 pandemic can find guidance in the recent AGA practice update, of which Dr. Rubin was the lead author. Clinicians who would like to contribute to the SECURE-IBD registry may do so at covidibd.org. The registry now includes more than 1,000 patients.

The study was funded by Clinical and Translational Science Award grants through Dr. Ungaro. The investigators disclosed relationships with Takeda, Janssen, Pfizer, and others. Dr. Rubin disclosed relationships with Gilead, Eli Lilly, Shire, and others.

SOURCE: Brenner EJ et al. Gastroenterology. 2020 May 18. doi: 10.1053/j.gastro.2020.05.032.

For patients with inflammatory bowel disease (IBD) who develop coronavirus disease of 2019 (COVID-19), corticosteroid use may significantly increase risk of severe disease, according to data from more than 500 patients.

Use of sulfasalazine or 5-aminosalicylates (5-ASAs) also increased risk of severe COVID-19, albeit to a lesser degree, reported co-lead authors Erica J. Brenner, MD, of University of North Carolina Children’s Hospital, Chapel Hill, and Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues.

In contrast, tumor necrosis factor (TNF) blockers were not an independent risk factor for severe COVID-19.

“As TNF antagonists are the most commonly prescribed biologic therapy for patients with IBD, these initial findings should be reassuring to the large number of patients receiving TNF antagonist therapy and support their continued use during this current pandemic,” the investigators wrote in Gastroenterology.

These conclusions were drawn from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) database, a large registry actively collecting data from clinicians around the world.

In the present analysis, which involved 525 patients from 33 countries, the investigators searched for independent risk factors for severe COVID-19. Various factors were tested through multivariable regression, including age, comorbidities, usage of specific medications, and more.

The primary outcome was defined by a composite of hospitalization, ventilator use, or death, while secondary outcomes included a composite of hospitalization or death, as well as death alone.

The analysis revealed that patients receiving corticosteroids had an adjusted odds ratio of 6.87 (95% confidence interval, 2.30-20.51) for severe COVID-19, with increased risks also detected for both secondary outcomes. In contrast, TNF antagonist use was not significantly associated with the primary outcome; in fact, a possible protective effect was detected for hospitalization or death (aOR, 0.60; 95% CI, 0.38-0.96).

The investigators noted that the above findings aligned with extensive literature concerning infectious complications with corticosteroid use and “more recent commentary” surrounding TNF antagonists. Similarly, increased age and the presence of at least two comorbidities were each independently associated with increased risk of severe COVID-19, both of which are correlations that have been previously described.

But the threefold increased risk of severe COVID-19 associated with use of sulfasalazine or 5-ASAs (aOR, 3.14; 95% CI, 1.28-7.71) was a “surprising” finding, the investigators noted.

“In a direct comparison, we observed that 5-ASA/sulfasalazine–treated patients fared worse than those treated with TNF inhibitors,” the investigators wrote. “Although we cannot exclude unmeasured confounding, further exploration of biological mechanisms is warranted.”

David T. Rubin, MD, of the University of Chicago agreed that the finding deserves further investigation, particularly since sulfasalazine and 5-ASAs represent the second most commonly prescribed medication class for IBD.

“The risk with 5-ASAs is of interest but not well explained by what we know about the safety or the mechanism of these therapies,” Dr. Rubin said. “Clearly, more work is needed.”

The risks associated with corticosteroids were particularly concerning, Dr. Rubin said, because 10%-20% of patients with IBD may be taking corticosteroids at any given time.

“Steroids are still the number one prescribed therapy for Crohn’s and colitis,” he said.

Still, Dr. Rubin advised against abrupt changes to drug regimens, especially if they are effectively controlling IBD.

“Patients should stay on their existing therapies and stay in remission,” Dr. Rubin said. “If you stop your therapies … you are more likely to relapse. When you relapse, you’re more likely to need steroids as a rescue therapy … or end up in the hospital, and those are not places we want you to be.”

Despite the risks associated with steroids and sulfasalazine/5-ASAs, Dr. Rubin had an optimistic take on the study, calling the findings “very reassuring” because they support continued usage of TNF inhibitors and other biologic agents during the pandemic. He also noted that the SECURE-IBD registry, which he has contributed to, represents “an extraordinary effort” from around the world.

“[This is] an unprecedented collaboration across a scale and timeframe that has really never been seen before in our field, and I would hazard a guess that it’s probably never been seen in most other fields right now,” he said.

Clinicians seeking more information about managing patients with IBD during the COVID-19 pandemic can find guidance in the recent AGA practice update, of which Dr. Rubin was the lead author. Clinicians who would like to contribute to the SECURE-IBD registry may do so at covidibd.org. The registry now includes more than 1,000 patients.

The study was funded by Clinical and Translational Science Award grants through Dr. Ungaro. The investigators disclosed relationships with Takeda, Janssen, Pfizer, and others. Dr. Rubin disclosed relationships with Gilead, Eli Lilly, Shire, and others.

SOURCE: Brenner EJ et al. Gastroenterology. 2020 May 18. doi: 10.1053/j.gastro.2020.05.032.

For patients with inflammatory bowel disease (IBD) who develop coronavirus disease of 2019 (COVID-19), corticosteroid use may significantly increase risk of severe disease, according to data from more than 500 patients.

Use of sulfasalazine or 5-aminosalicylates (5-ASAs) also increased risk of severe COVID-19, albeit to a lesser degree, reported co-lead authors Erica J. Brenner, MD, of University of North Carolina Children’s Hospital, Chapel Hill, and Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues.

In contrast, tumor necrosis factor (TNF) blockers were not an independent risk factor for severe COVID-19.

“As TNF antagonists are the most commonly prescribed biologic therapy for patients with IBD, these initial findings should be reassuring to the large number of patients receiving TNF antagonist therapy and support their continued use during this current pandemic,” the investigators wrote in Gastroenterology.

These conclusions were drawn from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) database, a large registry actively collecting data from clinicians around the world.

In the present analysis, which involved 525 patients from 33 countries, the investigators searched for independent risk factors for severe COVID-19. Various factors were tested through multivariable regression, including age, comorbidities, usage of specific medications, and more.

The primary outcome was defined by a composite of hospitalization, ventilator use, or death, while secondary outcomes included a composite of hospitalization or death, as well as death alone.

The analysis revealed that patients receiving corticosteroids had an adjusted odds ratio of 6.87 (95% confidence interval, 2.30-20.51) for severe COVID-19, with increased risks also detected for both secondary outcomes. In contrast, TNF antagonist use was not significantly associated with the primary outcome; in fact, a possible protective effect was detected for hospitalization or death (aOR, 0.60; 95% CI, 0.38-0.96).

The investigators noted that the above findings aligned with extensive literature concerning infectious complications with corticosteroid use and “more recent commentary” surrounding TNF antagonists. Similarly, increased age and the presence of at least two comorbidities were each independently associated with increased risk of severe COVID-19, both of which are correlations that have been previously described.

But the threefold increased risk of severe COVID-19 associated with use of sulfasalazine or 5-ASAs (aOR, 3.14; 95% CI, 1.28-7.71) was a “surprising” finding, the investigators noted.

“In a direct comparison, we observed that 5-ASA/sulfasalazine–treated patients fared worse than those treated with TNF inhibitors,” the investigators wrote. “Although we cannot exclude unmeasured confounding, further exploration of biological mechanisms is warranted.”

David T. Rubin, MD, of the University of Chicago agreed that the finding deserves further investigation, particularly since sulfasalazine and 5-ASAs represent the second most commonly prescribed medication class for IBD.

“The risk with 5-ASAs is of interest but not well explained by what we know about the safety or the mechanism of these therapies,” Dr. Rubin said. “Clearly, more work is needed.”

The risks associated with corticosteroids were particularly concerning, Dr. Rubin said, because 10%-20% of patients with IBD may be taking corticosteroids at any given time.

“Steroids are still the number one prescribed therapy for Crohn’s and colitis,” he said.

Still, Dr. Rubin advised against abrupt changes to drug regimens, especially if they are effectively controlling IBD.

“Patients should stay on their existing therapies and stay in remission,” Dr. Rubin said. “If you stop your therapies … you are more likely to relapse. When you relapse, you’re more likely to need steroids as a rescue therapy … or end up in the hospital, and those are not places we want you to be.”

Despite the risks associated with steroids and sulfasalazine/5-ASAs, Dr. Rubin had an optimistic take on the study, calling the findings “very reassuring” because they support continued usage of TNF inhibitors and other biologic agents during the pandemic. He also noted that the SECURE-IBD registry, which he has contributed to, represents “an extraordinary effort” from around the world.

“[This is] an unprecedented collaboration across a scale and timeframe that has really never been seen before in our field, and I would hazard a guess that it’s probably never been seen in most other fields right now,” he said.

Clinicians seeking more information about managing patients with IBD during the COVID-19 pandemic can find guidance in the recent AGA practice update, of which Dr. Rubin was the lead author. Clinicians who would like to contribute to the SECURE-IBD registry may do so at covidibd.org. The registry now includes more than 1,000 patients.

The study was funded by Clinical and Translational Science Award grants through Dr. Ungaro. The investigators disclosed relationships with Takeda, Janssen, Pfizer, and others. Dr. Rubin disclosed relationships with Gilead, Eli Lilly, Shire, and others.

SOURCE: Brenner EJ et al. Gastroenterology. 2020 May 18. doi: 10.1053/j.gastro.2020.05.032.

Potential risks of cardiac injury posed by coronavirus disease 2019 (COVID-19) infection warrant a cautious return-to-play for highly active people and competitive athletes who test positive, according to leading sports cardiologists.

To prevent cardiac injury, athletes should rest for at least 2 weeks after symptoms resolve, then undergo cardiac testing before returning high-level competitive sports, reported lead author Dermot Phelan, MD, PhD, of Atrium Health in Charlotte, N.C., and colleagues.

These recommendations, which were published in JAMA Cardiology, are part of a clinical algorithm that sorts athletes based on coronavirus test status and symptom severity. The algorithm offers a clear timeline for resumption of activity, with management decisions for symptomatic individuals based on additional diagnostics, such as high-sensitivity troponin testing and electrocardiogram.

Despite a scarcity of relevant clinical data, Dr. Phelan said that he and his colleagues wanted to offer their best recommendations to the athletic community, who had been reaching out for help.

“We were getting calls and messages from amateur and professional sporting organizations from around the country asking for guidance about what to do,” Dr. Phelan said. “So a number of us from the American College of Cardiology Sports and Exercise Council decided that we really should provide some guidance even in the absence of good, strong data, for what we feel is a reasonable approach.”

The recommendations were based on what is known of other viral infections, as well as risks posed by COVID-19 that may be worsened by athletic activity.

“We know that, when people have an active infection, vigorous exercise can lower immunity, and that can make the infection worse,” Dr. Phelan said. “That really applies very strongly in people who have had myocarditis. If you exercise when you have myocarditis, it actually increases viral replication and results in increased necrosis of the heart muscle. We really want to avoid exercising during that active infection phase.”

Myocarditis is one of the top causes of sudden cardiac death among young athletes, Dr. Phelan said, “so that’s a major concern for us.”

According to Dr. Phelan, existing data suggest a wide range of incidence of 7%-33% for cardiac injury among patients hospitalized for COVID-19. Even the low end of this range, at 7%, is significantly higher than the incidence rate of 1% found in patients with non–COVID-19 acute viral infections.

“This particular virus appears to cause more cardiac insults than other viruses,” Dr. Phelan said.

The incidence of cardiac injury among nonhospitalized patients remains unknown, leaving a wide knowledge gap that shaped the conservative nature of the present recommendations.

With more information, however, the guidance may “change dramatically,” Dr. Phelan said.

“If the data come back and show that no nonhospitalized patients got cardiac injury, then we would be much more comfortable allowing return to play without the need for cardiac testing,” he said.

Conversely, if cardiac injury is more common than anticipated, then more extensive testing may be needed, he added.

As the algorithm stands, high-sensitivity troponin testing and/or cardiac studies are recommended for all symptomatic athletes; if troponin levels are greater than the 99th percentile or a cardiac study is abnormal, then clinicians should follow return-to-play guidelines for myocarditis. For athletes with normal tests, slow resumption of activity is recommended, including close monitoring for clinical deterioration.

As Dr. Phelan discussed these recommendations in a broader context, he emphasized the need for caution, both preventively, and for cardiologists working with recovering athletes.

“For the early stage of this reentry into normal life while this is still an active pandemic, we need to be cautious,” Dr. Phelan said. “We need to follow the regular CDC guidelines, in terms of social distancing and handwashing, but we also need to consider that those people who have suffered from COVID-19 may have had cardiac injury. We don’t know that yet. But we need to be cautious with these individuals and test them before they return to high-level competitive sports.”

One author disclosed a relationship with the Atlanta Falcons.

SOURCE: Phelan D et al. JAMA Cardiology. 2020 Apr 13. doi: 10.1001/jamacardio.2020.2136.

Potential risks of cardiac injury posed by coronavirus disease 2019 (COVID-19) infection warrant a cautious return-to-play for highly active people and competitive athletes who test positive, according to leading sports cardiologists.

To prevent cardiac injury, athletes should rest for at least 2 weeks after symptoms resolve, then undergo cardiac testing before returning high-level competitive sports, reported lead author Dermot Phelan, MD, PhD, of Atrium Health in Charlotte, N.C., and colleagues.

These recommendations, which were published in JAMA Cardiology, are part of a clinical algorithm that sorts athletes based on coronavirus test status and symptom severity. The algorithm offers a clear timeline for resumption of activity, with management decisions for symptomatic individuals based on additional diagnostics, such as high-sensitivity troponin testing and electrocardiogram.

Despite a scarcity of relevant clinical data, Dr. Phelan said that he and his colleagues wanted to offer their best recommendations to the athletic community, who had been reaching out for help.

“We were getting calls and messages from amateur and professional sporting organizations from around the country asking for guidance about what to do,” Dr. Phelan said. “So a number of us from the American College of Cardiology Sports and Exercise Council decided that we really should provide some guidance even in the absence of good, strong data, for what we feel is a reasonable approach.”

The recommendations were based on what is known of other viral infections, as well as risks posed by COVID-19 that may be worsened by athletic activity.

“We know that, when people have an active infection, vigorous exercise can lower immunity, and that can make the infection worse,” Dr. Phelan said. “That really applies very strongly in people who have had myocarditis. If you exercise when you have myocarditis, it actually increases viral replication and results in increased necrosis of the heart muscle. We really want to avoid exercising during that active infection phase.”

Myocarditis is one of the top causes of sudden cardiac death among young athletes, Dr. Phelan said, “so that’s a major concern for us.”

According to Dr. Phelan, existing data suggest a wide range of incidence of 7%-33% for cardiac injury among patients hospitalized for COVID-19. Even the low end of this range, at 7%, is significantly higher than the incidence rate of 1% found in patients with non–COVID-19 acute viral infections.

“This particular virus appears to cause more cardiac insults than other viruses,” Dr. Phelan said.

The incidence of cardiac injury among nonhospitalized patients remains unknown, leaving a wide knowledge gap that shaped the conservative nature of the present recommendations.

With more information, however, the guidance may “change dramatically,” Dr. Phelan said.

“If the data come back and show that no nonhospitalized patients got cardiac injury, then we would be much more comfortable allowing return to play without the need for cardiac testing,” he said.

Conversely, if cardiac injury is more common than anticipated, then more extensive testing may be needed, he added.

As the algorithm stands, high-sensitivity troponin testing and/or cardiac studies are recommended for all symptomatic athletes; if troponin levels are greater than the 99th percentile or a cardiac study is abnormal, then clinicians should follow return-to-play guidelines for myocarditis. For athletes with normal tests, slow resumption of activity is recommended, including close monitoring for clinical deterioration.

As Dr. Phelan discussed these recommendations in a broader context, he emphasized the need for caution, both preventively, and for cardiologists working with recovering athletes.

“For the early stage of this reentry into normal life while this is still an active pandemic, we need to be cautious,” Dr. Phelan said. “We need to follow the regular CDC guidelines, in terms of social distancing and handwashing, but we also need to consider that those people who have suffered from COVID-19 may have had cardiac injury. We don’t know that yet. But we need to be cautious with these individuals and test them before they return to high-level competitive sports.”

One author disclosed a relationship with the Atlanta Falcons.

SOURCE: Phelan D et al. JAMA Cardiology. 2020 Apr 13. doi: 10.1001/jamacardio.2020.2136.

Potential risks of cardiac injury posed by coronavirus disease 2019 (COVID-19) infection warrant a cautious return-to-play for highly active people and competitive athletes who test positive, according to leading sports cardiologists.

To prevent cardiac injury, athletes should rest for at least 2 weeks after symptoms resolve, then undergo cardiac testing before returning high-level competitive sports, reported lead author Dermot Phelan, MD, PhD, of Atrium Health in Charlotte, N.C., and colleagues.

These recommendations, which were published in JAMA Cardiology, are part of a clinical algorithm that sorts athletes based on coronavirus test status and symptom severity. The algorithm offers a clear timeline for resumption of activity, with management decisions for symptomatic individuals based on additional diagnostics, such as high-sensitivity troponin testing and electrocardiogram.

Despite a scarcity of relevant clinical data, Dr. Phelan said that he and his colleagues wanted to offer their best recommendations to the athletic community, who had been reaching out for help.

“We were getting calls and messages from amateur and professional sporting organizations from around the country asking for guidance about what to do,” Dr. Phelan said. “So a number of us from the American College of Cardiology Sports and Exercise Council decided that we really should provide some guidance even in the absence of good, strong data, for what we feel is a reasonable approach.”

The recommendations were based on what is known of other viral infections, as well as risks posed by COVID-19 that may be worsened by athletic activity.

“We know that, when people have an active infection, vigorous exercise can lower immunity, and that can make the infection worse,” Dr. Phelan said. “That really applies very strongly in people who have had myocarditis. If you exercise when you have myocarditis, it actually increases viral replication and results in increased necrosis of the heart muscle. We really want to avoid exercising during that active infection phase.”

Myocarditis is one of the top causes of sudden cardiac death among young athletes, Dr. Phelan said, “so that’s a major concern for us.”

According to Dr. Phelan, existing data suggest a wide range of incidence of 7%-33% for cardiac injury among patients hospitalized for COVID-19. Even the low end of this range, at 7%, is significantly higher than the incidence rate of 1% found in patients with non–COVID-19 acute viral infections.

“This particular virus appears to cause more cardiac insults than other viruses,” Dr. Phelan said.

The incidence of cardiac injury among nonhospitalized patients remains unknown, leaving a wide knowledge gap that shaped the conservative nature of the present recommendations.

With more information, however, the guidance may “change dramatically,” Dr. Phelan said.

“If the data come back and show that no nonhospitalized patients got cardiac injury, then we would be much more comfortable allowing return to play without the need for cardiac testing,” he said.

Conversely, if cardiac injury is more common than anticipated, then more extensive testing may be needed, he added.

As the algorithm stands, high-sensitivity troponin testing and/or cardiac studies are recommended for all symptomatic athletes; if troponin levels are greater than the 99th percentile or a cardiac study is abnormal, then clinicians should follow return-to-play guidelines for myocarditis. For athletes with normal tests, slow resumption of activity is recommended, including close monitoring for clinical deterioration.

As Dr. Phelan discussed these recommendations in a broader context, he emphasized the need for caution, both preventively, and for cardiologists working with recovering athletes.

“For the early stage of this reentry into normal life while this is still an active pandemic, we need to be cautious,” Dr. Phelan said. “We need to follow the regular CDC guidelines, in terms of social distancing and handwashing, but we also need to consider that those people who have suffered from COVID-19 may have had cardiac injury. We don’t know that yet. But we need to be cautious with these individuals and test them before they return to high-level competitive sports.”

One author disclosed a relationship with the Atlanta Falcons.

SOURCE: Phelan D et al. JAMA Cardiology. 2020 Apr 13. doi: 10.1001/jamacardio.2020.2136.

Despite an increasing rate of obesity in the United States, sleeve gastrectomy and postoperative antiobesity pharmacotherapy remain significantly underutilized, according to investigators.

A retrospective study involving almost 3 million adults with obesity found that only 0.94% had undergone sleeve gastrectomy, with 5.6% of those receiving weight-loss drugs after discharge, reported lead author Raj Shah, MD, of University Hospitals Cleveland Medical Center, and colleagues.

“While obesity has increased exponentially in the past decade, the trends of bariatric procedures and postoperative pharmacotherapy in this timeline is not well established,” the investigators wrote in an abstract released as part of the annual Digestive Disease Week, which was canceled because of COVID-19.

According to coauthor Abbinaya Elangovan, MD, of MetroHealth Medical Center, Cleveland, existing data suggest a practice gap.

“We know from published studies that antiobesity measures – both surgical and pharmacotherapeutic – do not match the rates of obesity,” Dr. Elangovan said. “We wanted to see how many of the morbidly obese [patients] who get bariatric surgery get started on antiobesity pharmacotherapy. We selected sleeve gastrectomy, as that is the most common bariatric procedure performed in the United States in recent times.”

The investigators began by retrospectively screening 2,717,000 individuals with a body mass index (in kg/m₂) of at least 40 who entered the IBM Explorys database from 2010 to 2019. Out of this group, 25,540 individuals (0.94%) had undergone sleeve gastrectomy. Annual rates of the procedure increased from 0.06% in 2010 to 0.4% in 2019 (P < .0001).

Of the 25,540 patients who underwent sleeve gastrectomy, 1,440 (5.6%) were prescribed antiobesity medication after surgery, with about half (47%) of these prescriptions written within a year. The most common medication was phentermine (66%), followed by bupropion/naltrexone (16%) and phentermine/topiramate (14.4%).

Dr. Elangovan said that the rates of surgery and antiobesity pharmacotherapy found in the study were “sparse” compared with rates of obesity.

“[Future studies need] to find the barriers to antiobesity pharmacotherapy,” Dr. Elangovan said. “We know from some of the published studies that there are differences in provider perceptions, as well as patient populations who get the therapy.”

The present analysis showed that women, African Americans, and patients with commercial insurance were significantly more likely to receive postoperative weight-loss medications than other patient subgroups.

“I think insurance could be a potential concern,” Dr. Elangovan said. “This has been shown previously in the literature.” She also suggested that women may be accessing obesity-related health care more often than men.

Discussing steps to improve interventions for patients with obesity, Dr. Elangovan emphasized the amount of data supporting antiobesity pharmacotherapy.

“We know from studies published so far that combining pharmacotherapy with behavioral modifications has a greater percentage of success, compared to behavioral modifications by themselves,” Dr. Elangovan said.

According to Dr. Elangovan, primary care providers play a key role in connecting obese patients with the treatments they need, requiring familiarity with existing guidelines.

“It helps if practicing clinicians, especially primary care providers, are familiar with bariatric surgery criteria and institution policies,” Dr. Elangovan said. “It has been shown in some studies that limited experience in prescribing and concern for adverse reactions could affect the prescription of antiobesity pharmacotherapy. Targeted interventions such as educational programs may increase the appropriate usage of medications.”

Dr. Smith disclosed a relationship with US Endoscopy.

SOURCE: Shah R et al. DDW 2020, Abstract 791.

Despite an increasing rate of obesity in the United States, sleeve gastrectomy and postoperative antiobesity pharmacotherapy remain significantly underutilized, according to investigators.

A retrospective study involving almost 3 million adults with obesity found that only 0.94% had undergone sleeve gastrectomy, with 5.6% of those receiving weight-loss drugs after discharge, reported lead author Raj Shah, MD, of University Hospitals Cleveland Medical Center, and colleagues.

“While obesity has increased exponentially in the past decade, the trends of bariatric procedures and postoperative pharmacotherapy in this timeline is not well established,” the investigators wrote in an abstract released as part of the annual Digestive Disease Week, which was canceled because of COVID-19.

According to coauthor Abbinaya Elangovan, MD, of MetroHealth Medical Center, Cleveland, existing data suggest a practice gap.

“We know from published studies that antiobesity measures – both surgical and pharmacotherapeutic – do not match the rates of obesity,” Dr. Elangovan said. “We wanted to see how many of the morbidly obese [patients] who get bariatric surgery get started on antiobesity pharmacotherapy. We selected sleeve gastrectomy, as that is the most common bariatric procedure performed in the United States in recent times.”

The investigators began by retrospectively screening 2,717,000 individuals with a body mass index (in kg/m₂) of at least 40 who entered the IBM Explorys database from 2010 to 2019. Out of this group, 25,540 individuals (0.94%) had undergone sleeve gastrectomy. Annual rates of the procedure increased from 0.06% in 2010 to 0.4% in 2019 (P < .0001).

Of the 25,540 patients who underwent sleeve gastrectomy, 1,440 (5.6%) were prescribed antiobesity medication after surgery, with about half (47%) of these prescriptions written within a year. The most common medication was phentermine (66%), followed by bupropion/naltrexone (16%) and phentermine/topiramate (14.4%).

Dr. Elangovan said that the rates of surgery and antiobesity pharmacotherapy found in the study were “sparse” compared with rates of obesity.

“[Future studies need] to find the barriers to antiobesity pharmacotherapy,” Dr. Elangovan said. “We know from some of the published studies that there are differences in provider perceptions, as well as patient populations who get the therapy.”

The present analysis showed that women, African Americans, and patients with commercial insurance were significantly more likely to receive postoperative weight-loss medications than other patient subgroups.

“I think insurance could be a potential concern,” Dr. Elangovan said. “This has been shown previously in the literature.” She also suggested that women may be accessing obesity-related health care more often than men.

Discussing steps to improve interventions for patients with obesity, Dr. Elangovan emphasized the amount of data supporting antiobesity pharmacotherapy.

“We know from studies published so far that combining pharmacotherapy with behavioral modifications has a greater percentage of success, compared to behavioral modifications by themselves,” Dr. Elangovan said.

According to Dr. Elangovan, primary care providers play a key role in connecting obese patients with the treatments they need, requiring familiarity with existing guidelines.

“It helps if practicing clinicians, especially primary care providers, are familiar with bariatric surgery criteria and institution policies,” Dr. Elangovan said. “It has been shown in some studies that limited experience in prescribing and concern for adverse reactions could affect the prescription of antiobesity pharmacotherapy. Targeted interventions such as educational programs may increase the appropriate usage of medications.”

Dr. Smith disclosed a relationship with US Endoscopy.

SOURCE: Shah R et al. DDW 2020, Abstract 791.

Despite an increasing rate of obesity in the United States, sleeve gastrectomy and postoperative antiobesity pharmacotherapy remain significantly underutilized, according to investigators.

A retrospective study involving almost 3 million adults with obesity found that only 0.94% had undergone sleeve gastrectomy, with 5.6% of those receiving weight-loss drugs after discharge, reported lead author Raj Shah, MD, of University Hospitals Cleveland Medical Center, and colleagues.

“While obesity has increased exponentially in the past decade, the trends of bariatric procedures and postoperative pharmacotherapy in this timeline is not well established,” the investigators wrote in an abstract released as part of the annual Digestive Disease Week, which was canceled because of COVID-19.

According to coauthor Abbinaya Elangovan, MD, of MetroHealth Medical Center, Cleveland, existing data suggest a practice gap.

“We know from published studies that antiobesity measures – both surgical and pharmacotherapeutic – do not match the rates of obesity,” Dr. Elangovan said. “We wanted to see how many of the morbidly obese [patients] who get bariatric surgery get started on antiobesity pharmacotherapy. We selected sleeve gastrectomy, as that is the most common bariatric procedure performed in the United States in recent times.”

The investigators began by retrospectively screening 2,717,000 individuals with a body mass index (in kg/m₂) of at least 40 who entered the IBM Explorys database from 2010 to 2019. Out of this group, 25,540 individuals (0.94%) had undergone sleeve gastrectomy. Annual rates of the procedure increased from 0.06% in 2010 to 0.4% in 2019 (P < .0001).

Of the 25,540 patients who underwent sleeve gastrectomy, 1,440 (5.6%) were prescribed antiobesity medication after surgery, with about half (47%) of these prescriptions written within a year. The most common medication was phentermine (66%), followed by bupropion/naltrexone (16%) and phentermine/topiramate (14.4%).

Dr. Elangovan said that the rates of surgery and antiobesity pharmacotherapy found in the study were “sparse” compared with rates of obesity.

“[Future studies need] to find the barriers to antiobesity pharmacotherapy,” Dr. Elangovan said. “We know from some of the published studies that there are differences in provider perceptions, as well as patient populations who get the therapy.”

The present analysis showed that women, African Americans, and patients with commercial insurance were significantly more likely to receive postoperative weight-loss medications than other patient subgroups.

“I think insurance could be a potential concern,” Dr. Elangovan said. “This has been shown previously in the literature.” She also suggested that women may be accessing obesity-related health care more often than men.

Discussing steps to improve interventions for patients with obesity, Dr. Elangovan emphasized the amount of data supporting antiobesity pharmacotherapy.

“We know from studies published so far that combining pharmacotherapy with behavioral modifications has a greater percentage of success, compared to behavioral modifications by themselves,” Dr. Elangovan said.

According to Dr. Elangovan, primary care providers play a key role in connecting obese patients with the treatments they need, requiring familiarity with existing guidelines.

“It helps if practicing clinicians, especially primary care providers, are familiar with bariatric surgery criteria and institution policies,” Dr. Elangovan said. “It has been shown in some studies that limited experience in prescribing and concern for adverse reactions could affect the prescription of antiobesity pharmacotherapy. Targeted interventions such as educational programs may increase the appropriate usage of medications.”

Dr. Smith disclosed a relationship with US Endoscopy.

SOURCE: Shah R et al. DDW 2020, Abstract 791.