Andrew D. Bowser

Duvelisib is demonstrating encouraging activity and manageable toxicities among patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) in a phase 2 trial, an investigator said.

The overall response rate in the dose-optimization phase of the PRIMO trial was more than 60% among patients receiving 75 mg of duvelisib twice daily, with a median duration of response exceeding 12 months, said investigator Barbara Pro, MD, of Northwestern University, Chicago.

In the ongoing dose-expansion phase, in which patients start on 75 mg twice daily and then transition to a lower dose, the ORR is over 50%, including complete responses (CRs) in about one-third of patients, Dr. Pro reported at the annual meeting of the American Society of Hematology.

Most previously approved treatments for relapsed/refractory PTCL are associated with ORRs of less than 30%, low rates of CR, and median progression-free survival of less than 4 months, Dr. Pro said in her presentation.

There have been no unexpected toxicities in the dose-expansion phase, and the adverse event profile is consistent with what has been observed previously for this oral phosphatidylinositol 3-kinase (PI3K) inhibitor, according to Dr. Pro.

Based on results to date, Dr. Pro said she and coinvestigators are hopeful that duvelisib will have a place in the treatment armamentarium for relapsed/refractory PTCL in the future.

“This is one of the most effective agents in T-cell lymphoma, and hopefully will be approved and available for treatment soon,” she said in remarks following her presentation of PRIMO study data.

“The next question would be how to try to move this agent up front,” she added. “We’ll have to try to see what could be the possible combinations and evaluate the possible overlapping toxicity with alternative treatments.”

The PRIMO trial provides “very exciting numbers” that include roughly half of relapsed/refractory PTCL patients are responding to the oral therapy, said Andrei R. Shustov, MD, professor of medicine in the division of hematology at the University of Washington, Seattle.

Perhaps more importantly, at least half of those responses have been CRs, Dr. Shustov noted in an interview: “We haven’t seen this yet in T-cell lymphomas, short of brentuximab vedotin targeting CD30,” he said, referring to the 2018 Food and Drug Administration approval of brentuximab vedotin for previously untreated CD30-expressing PTCL.

If duvelisib is approved, it would be the first oral agent with an indication for relapsed/refractory PTCL, which could have important implications for patient quality of life, Dr. Shustov added.

“The fact that you can take a pill at home, and don’t have to be in clinic once a week, or have the port device, or be infused every week would be an incredible change in quality of life,” he said, “and this is really amplified in the older population where quality of life is so important.”

Duvelisib was FDA approved in 2018, at a dose of 25 mg orally twice daily, for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma, and follicular lymphoma, following at least two previous treatments.

In relapsed/refractory PTCL, results of a phase 1 study previously published in Blood showed that duvelisib demonstrated an ORR of 50%, or 8 out of 16 patients treated with 25 or 75 mg twice daily continuously.

The phase 2 study described by Dr. Pro at this year’s ASH meeting included 33 patients with relapsed/refractory PTCL treated with duvelisib 25 mg or 75 mg twice daily as part of a dose-optimization phase, and 25 patients treated in an expansion phase at 75 mg twice daily for two 28-day cycles, followed by treatment at 25 mg twice daily.

Starting at the higher dose of 75 mg twice daily is intended to achieve rapid tumor control, while switching to the lower 25-mg twice-daily dose is to maintain long-term control of the disease while mitigating potential for later toxicities, according to the published abstract for the PRIMO trial.

Results of the dose-optimization phase included an ORR by independent review committee of 62% for patients treated at the 75-mg twice-daily dose, and 40% for those treated at 25 mg twice daily. The median duration of response in the 75-mg twice-daily group was 12.2 months, which Dr. Pro said was significantly higher than what was observed for the lower dose.

In the ongoing dose-expansion phase, the ORR by investigator was 52% (13 of 25 patients), with a CR rate of 36% (9 of 25 patients). The reported data show that with a median duration of follow-up of 3.78 months, the median duration of response thus far is 4.1 months.

The most common grade 3 or higher adverse events were increases in ALT and AST, seen in 24% and 20% of patients, respectively. The most common grade 3 or greater hematologic toxicity was decreased lymphocyte count, seen in 16%.

Three serious treatment-emergent adverse events thought to be related to duvelisib occurred in two patients, including grade 5 pneumonitis in one patient, and skin lesion plus posttransplant lymphoproliferative disorder in the other patient, according to Dr. Pro. Serious treatment-emergent adverse events leading to duvelisib discontinuation included increased ALT/AST in 2 patients and pneumonitis in one patient.

Grade 1-2 adverse events reported at ASH included hypertension, nausea, anemia, fatigue, diarrhea, constipation and pyrexia, among others.

Enrollment in the dose-expansion phase of PRIMO is ongoing and should be complete in February, according to Dr. Pro.

Support for the study came from Verastem Oncology and Secura Bio. Dr. Pro reported research funding from Verastem Oncology, Takeda, and other pharmaceutical companies and honoraria from Takeda and Seattle Genetics.

SOURCE: Pro B et al. ASH 2020, Abstract 44.

Duvelisib is demonstrating encouraging activity and manageable toxicities among patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) in a phase 2 trial, an investigator said.

The overall response rate in the dose-optimization phase of the PRIMO trial was more than 60% among patients receiving 75 mg of duvelisib twice daily, with a median duration of response exceeding 12 months, said investigator Barbara Pro, MD, of Northwestern University, Chicago.

In the ongoing dose-expansion phase, in which patients start on 75 mg twice daily and then transition to a lower dose, the ORR is over 50%, including complete responses (CRs) in about one-third of patients, Dr. Pro reported at the annual meeting of the American Society of Hematology.

Most previously approved treatments for relapsed/refractory PTCL are associated with ORRs of less than 30%, low rates of CR, and median progression-free survival of less than 4 months, Dr. Pro said in her presentation.

There have been no unexpected toxicities in the dose-expansion phase, and the adverse event profile is consistent with what has been observed previously for this oral phosphatidylinositol 3-kinase (PI3K) inhibitor, according to Dr. Pro.

Based on results to date, Dr. Pro said she and coinvestigators are hopeful that duvelisib will have a place in the treatment armamentarium for relapsed/refractory PTCL in the future.

“This is one of the most effective agents in T-cell lymphoma, and hopefully will be approved and available for treatment soon,” she said in remarks following her presentation of PRIMO study data.

“The next question would be how to try to move this agent up front,” she added. “We’ll have to try to see what could be the possible combinations and evaluate the possible overlapping toxicity with alternative treatments.”

The PRIMO trial provides “very exciting numbers” that include roughly half of relapsed/refractory PTCL patients are responding to the oral therapy, said Andrei R. Shustov, MD, professor of medicine in the division of hematology at the University of Washington, Seattle.

Perhaps more importantly, at least half of those responses have been CRs, Dr. Shustov noted in an interview: “We haven’t seen this yet in T-cell lymphomas, short of brentuximab vedotin targeting CD30,” he said, referring to the 2018 Food and Drug Administration approval of brentuximab vedotin for previously untreated CD30-expressing PTCL.

If duvelisib is approved, it would be the first oral agent with an indication for relapsed/refractory PTCL, which could have important implications for patient quality of life, Dr. Shustov added.

“The fact that you can take a pill at home, and don’t have to be in clinic once a week, or have the port device, or be infused every week would be an incredible change in quality of life,” he said, “and this is really amplified in the older population where quality of life is so important.”

Duvelisib was FDA approved in 2018, at a dose of 25 mg orally twice daily, for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma, and follicular lymphoma, following at least two previous treatments.

In relapsed/refractory PTCL, results of a phase 1 study previously published in Blood showed that duvelisib demonstrated an ORR of 50%, or 8 out of 16 patients treated with 25 or 75 mg twice daily continuously.

The phase 2 study described by Dr. Pro at this year’s ASH meeting included 33 patients with relapsed/refractory PTCL treated with duvelisib 25 mg or 75 mg twice daily as part of a dose-optimization phase, and 25 patients treated in an expansion phase at 75 mg twice daily for two 28-day cycles, followed by treatment at 25 mg twice daily.

Starting at the higher dose of 75 mg twice daily is intended to achieve rapid tumor control, while switching to the lower 25-mg twice-daily dose is to maintain long-term control of the disease while mitigating potential for later toxicities, according to the published abstract for the PRIMO trial.

Results of the dose-optimization phase included an ORR by independent review committee of 62% for patients treated at the 75-mg twice-daily dose, and 40% for those treated at 25 mg twice daily. The median duration of response in the 75-mg twice-daily group was 12.2 months, which Dr. Pro said was significantly higher than what was observed for the lower dose.

In the ongoing dose-expansion phase, the ORR by investigator was 52% (13 of 25 patients), with a CR rate of 36% (9 of 25 patients). The reported data show that with a median duration of follow-up of 3.78 months, the median duration of response thus far is 4.1 months.

The most common grade 3 or higher adverse events were increases in ALT and AST, seen in 24% and 20% of patients, respectively. The most common grade 3 or greater hematologic toxicity was decreased lymphocyte count, seen in 16%.

Three serious treatment-emergent adverse events thought to be related to duvelisib occurred in two patients, including grade 5 pneumonitis in one patient, and skin lesion plus posttransplant lymphoproliferative disorder in the other patient, according to Dr. Pro. Serious treatment-emergent adverse events leading to duvelisib discontinuation included increased ALT/AST in 2 patients and pneumonitis in one patient.

Grade 1-2 adverse events reported at ASH included hypertension, nausea, anemia, fatigue, diarrhea, constipation and pyrexia, among others.

Enrollment in the dose-expansion phase of PRIMO is ongoing and should be complete in February, according to Dr. Pro.

Support for the study came from Verastem Oncology and Secura Bio. Dr. Pro reported research funding from Verastem Oncology, Takeda, and other pharmaceutical companies and honoraria from Takeda and Seattle Genetics.

SOURCE: Pro B et al. ASH 2020, Abstract 44.

Duvelisib is demonstrating encouraging activity and manageable toxicities among patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) in a phase 2 trial, an investigator said.

The overall response rate in the dose-optimization phase of the PRIMO trial was more than 60% among patients receiving 75 mg of duvelisib twice daily, with a median duration of response exceeding 12 months, said investigator Barbara Pro, MD, of Northwestern University, Chicago.

In the ongoing dose-expansion phase, in which patients start on 75 mg twice daily and then transition to a lower dose, the ORR is over 50%, including complete responses (CRs) in about one-third of patients, Dr. Pro reported at the annual meeting of the American Society of Hematology.

Most previously approved treatments for relapsed/refractory PTCL are associated with ORRs of less than 30%, low rates of CR, and median progression-free survival of less than 4 months, Dr. Pro said in her presentation.

There have been no unexpected toxicities in the dose-expansion phase, and the adverse event profile is consistent with what has been observed previously for this oral phosphatidylinositol 3-kinase (PI3K) inhibitor, according to Dr. Pro.

Based on results to date, Dr. Pro said she and coinvestigators are hopeful that duvelisib will have a place in the treatment armamentarium for relapsed/refractory PTCL in the future.

“This is one of the most effective agents in T-cell lymphoma, and hopefully will be approved and available for treatment soon,” she said in remarks following her presentation of PRIMO study data.

“The next question would be how to try to move this agent up front,” she added. “We’ll have to try to see what could be the possible combinations and evaluate the possible overlapping toxicity with alternative treatments.”

The PRIMO trial provides “very exciting numbers” that include roughly half of relapsed/refractory PTCL patients are responding to the oral therapy, said Andrei R. Shustov, MD, professor of medicine in the division of hematology at the University of Washington, Seattle.

Perhaps more importantly, at least half of those responses have been CRs, Dr. Shustov noted in an interview: “We haven’t seen this yet in T-cell lymphomas, short of brentuximab vedotin targeting CD30,” he said, referring to the 2018 Food and Drug Administration approval of brentuximab vedotin for previously untreated CD30-expressing PTCL.

If duvelisib is approved, it would be the first oral agent with an indication for relapsed/refractory PTCL, which could have important implications for patient quality of life, Dr. Shustov added.

“The fact that you can take a pill at home, and don’t have to be in clinic once a week, or have the port device, or be infused every week would be an incredible change in quality of life,” he said, “and this is really amplified in the older population where quality of life is so important.”

Duvelisib was FDA approved in 2018, at a dose of 25 mg orally twice daily, for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma, and follicular lymphoma, following at least two previous treatments.

In relapsed/refractory PTCL, results of a phase 1 study previously published in Blood showed that duvelisib demonstrated an ORR of 50%, or 8 out of 16 patients treated with 25 or 75 mg twice daily continuously.

The phase 2 study described by Dr. Pro at this year’s ASH meeting included 33 patients with relapsed/refractory PTCL treated with duvelisib 25 mg or 75 mg twice daily as part of a dose-optimization phase, and 25 patients treated in an expansion phase at 75 mg twice daily for two 28-day cycles, followed by treatment at 25 mg twice daily.

Starting at the higher dose of 75 mg twice daily is intended to achieve rapid tumor control, while switching to the lower 25-mg twice-daily dose is to maintain long-term control of the disease while mitigating potential for later toxicities, according to the published abstract for the PRIMO trial.

Results of the dose-optimization phase included an ORR by independent review committee of 62% for patients treated at the 75-mg twice-daily dose, and 40% for those treated at 25 mg twice daily. The median duration of response in the 75-mg twice-daily group was 12.2 months, which Dr. Pro said was significantly higher than what was observed for the lower dose.

In the ongoing dose-expansion phase, the ORR by investigator was 52% (13 of 25 patients), with a CR rate of 36% (9 of 25 patients). The reported data show that with a median duration of follow-up of 3.78 months, the median duration of response thus far is 4.1 months.

The most common grade 3 or higher adverse events were increases in ALT and AST, seen in 24% and 20% of patients, respectively. The most common grade 3 or greater hematologic toxicity was decreased lymphocyte count, seen in 16%.

Three serious treatment-emergent adverse events thought to be related to duvelisib occurred in two patients, including grade 5 pneumonitis in one patient, and skin lesion plus posttransplant lymphoproliferative disorder in the other patient, according to Dr. Pro. Serious treatment-emergent adverse events leading to duvelisib discontinuation included increased ALT/AST in 2 patients and pneumonitis in one patient.

Grade 1-2 adverse events reported at ASH included hypertension, nausea, anemia, fatigue, diarrhea, constipation and pyrexia, among others.

Enrollment in the dose-expansion phase of PRIMO is ongoing and should be complete in February, according to Dr. Pro.

Support for the study came from Verastem Oncology and Secura Bio. Dr. Pro reported research funding from Verastem Oncology, Takeda, and other pharmaceutical companies and honoraria from Takeda and Seattle Genetics.

SOURCE: Pro B et al. ASH 2020, Abstract 44.

In patients with T-cell lymphoma, allogeneic transplant can lead to durable remissions among patients who might otherwise have poor outcomes, results of a large retrospective observational study suggest.

Five-year progression-free survival (PFS) approached 40% and 5-year overall survival (OS) was over 50% in the study, which according to an investigator is the largest-ever reported patient series of allogeneic stem cell transplantation in T-cell lymphomas.

“We believe that eligible patients with relapsed/refractory T-cell lymphomas should be considered for consultation for allogeneic transplant by an expert clinician,” said investigator Neha Mehta-Shah, MD, of Washington University in St. Louis.

“These decisions should occur on a patient by patient level – but it’s important to consider this,” Dr. Mehta-Shah said at the annual meeting of the American Society of Hematology, held virtually this year.

Notably, patients with cutaneous T-cell lymphoma (CTCL) had a higher rate of relapse yet similar overall survival (OS) compared to patients with common peripheral T-cell lymphoma (PTCL) subtypes, according to Dr. Mehta-Shah.

Among PTCL subtypes, there was a trend toward improved PFS and OS for angioimmunoblastic T-cell lymphoma (AITL), compared with PTCL not otherwise specified (PTCL-NOS) and anaplastic large-cell lymphoma (ALCL), she added.

Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone’s Perlmutter Cancer Center, said the results of this retrospective study need to considered in light of the treatment-related risks associated with allogeneic transplantation.

Treatment-related mortality in the study ranged from about 8% to 24%, depending on the donor type, while acute and chronic graft-versus-host-disease (GvHD) was seen in more than 40% of patients, the reported data show.

“If I have a relapsed patient with AITL, I would look to this data and say that patients with AITL appear in a retrospective study to have a strong benefit,” Dr. Diefenbach said in an interview.

“For the other patients, you would describe both potential benefits and also discuss the treatment-associated risks – both the chronic GvHD and transplant-related mortality – and you’d have to balance the risk with the benefits for each individual case,” Dr. Diefenbach added.

The retrospective analysis by Dr. Mehta-Shah and colleagues included 508 consecutive T-cell lymphoma patients receiving allogeneic transplants at 12 academic centers between 2000 and 2019. The most common subtypes were PTCL-NOS in 26%, AITL in 16%, CTCL in 13%, and hepatosplenic T-cell lymphoma (HSTCL) in 7%. About 40% had a matched related donor (MRD) and 39% had a matched unrelated donor (MUD). The conditioning regimen was myeloablative in about a third of patients and nonmyeloablative in two-thirds.

At 5 years, PFS was 39.4% and OS was 50.8% for the overall study cohort, Dr. Mehta-Shah reported, noting that the median time from relapse to death post allogeneic transplant was 10.2 months.

Patients in complete remission at the time of transplant fared better than others, with a median PFS of 44.6 months vs. 8.5 months for those in partial remission, 21.0 months in those with stable disease, and 3.5 months for those with progressive disease at time of transplant, data show.

Patients with common PTCL subtypes had better PFS compared to patients with CTCL, yet OS was similar, according to the investigator. At 5 years, PFS was 43.7% and 18.6%, respectively, for PTCL and CTCL, while OS was 53.1% and 44.0%, respectively.

There was a trend toward improved outcomes for AITL relative to PTCL-NOS and ALCL, with a median PFS of 51.4 months for AITL versus 18.3 months those other subtypes. Similarly, median OS was not reached for AITL versus 73.1 months in the other subtypes.

Treatment-related mortality was lowest for patients with MRDs, or 8.2% at 12 months, Dr. Mehta-Shah reported, while patients with MUDs, mismatched donors, or haploidentical donors had treatment-related mortality of 13% to 16% at 12 months, and those with cord blood donors had treatment-related mortality of nearly 24% at 12 months.

Acute GvHD was observed in 46% of patients and chronic GvHD was seen in nearly 41%, the investigator added.

While these findings are important to consider in individual patient consultations, the study is nevertheless subject to limitations including patient selection and referral bias, according to Dr. Mehta-Shah.

“This was a retrospective analysis of patients who underwent transplant,” she said in a question-and-answer period. “Of course, that is heavily biased by who got to a transplant center, who was well enough to achieve transplant, and who had a donor or donor options, as well as their overall health and depth of remission,” the researcher said.

“I think this just represents what we could tell patients about what may happen to them once they embark on a transplant,” she added, “but really, there would be more prospective work needed to be done for what happens to patients overarching, and how many of them even get to a transplant consultation.”

Further studies should be done to develop predictive tools or biomarkers to determine who benefits from an allogeneic transplant, if there are predictors of relapse following allogeneic transplant, and what are the mechanisms of relapse following allogeneic transplant, according to Dr. Mehta-Shah.

Dr. Mehta-Shah reported research funding from Bristol Myers-Squibb, Celgene, Verastem, Corvus, Innate Pharmaceuticals, and Genentech/Roche. She reported consultancy with Kyowa Hakko Kirin, C4 Therapeutics, and Karyopharm Therapeutics.
 

SOURCE: Mehta-Shah N et al. ASH 2020, Abstract 41.

In patients with T-cell lymphoma, allogeneic transplant can lead to durable remissions among patients who might otherwise have poor outcomes, results of a large retrospective observational study suggest.

Five-year progression-free survival (PFS) approached 40% and 5-year overall survival (OS) was over 50% in the study, which according to an investigator is the largest-ever reported patient series of allogeneic stem cell transplantation in T-cell lymphomas.

“We believe that eligible patients with relapsed/refractory T-cell lymphomas should be considered for consultation for allogeneic transplant by an expert clinician,” said investigator Neha Mehta-Shah, MD, of Washington University in St. Louis.

“These decisions should occur on a patient by patient level – but it’s important to consider this,” Dr. Mehta-Shah said at the annual meeting of the American Society of Hematology, held virtually this year.

Notably, patients with cutaneous T-cell lymphoma (CTCL) had a higher rate of relapse yet similar overall survival (OS) compared to patients with common peripheral T-cell lymphoma (PTCL) subtypes, according to Dr. Mehta-Shah.

Among PTCL subtypes, there was a trend toward improved PFS and OS for angioimmunoblastic T-cell lymphoma (AITL), compared with PTCL not otherwise specified (PTCL-NOS) and anaplastic large-cell lymphoma (ALCL), she added.

Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone’s Perlmutter Cancer Center, said the results of this retrospective study need to considered in light of the treatment-related risks associated with allogeneic transplantation.

Treatment-related mortality in the study ranged from about 8% to 24%, depending on the donor type, while acute and chronic graft-versus-host-disease (GvHD) was seen in more than 40% of patients, the reported data show.

“If I have a relapsed patient with AITL, I would look to this data and say that patients with AITL appear in a retrospective study to have a strong benefit,” Dr. Diefenbach said in an interview.

“For the other patients, you would describe both potential benefits and also discuss the treatment-associated risks – both the chronic GvHD and transplant-related mortality – and you’d have to balance the risk with the benefits for each individual case,” Dr. Diefenbach added.

The retrospective analysis by Dr. Mehta-Shah and colleagues included 508 consecutive T-cell lymphoma patients receiving allogeneic transplants at 12 academic centers between 2000 and 2019. The most common subtypes were PTCL-NOS in 26%, AITL in 16%, CTCL in 13%, and hepatosplenic T-cell lymphoma (HSTCL) in 7%. About 40% had a matched related donor (MRD) and 39% had a matched unrelated donor (MUD). The conditioning regimen was myeloablative in about a third of patients and nonmyeloablative in two-thirds.

At 5 years, PFS was 39.4% and OS was 50.8% for the overall study cohort, Dr. Mehta-Shah reported, noting that the median time from relapse to death post allogeneic transplant was 10.2 months.

Patients in complete remission at the time of transplant fared better than others, with a median PFS of 44.6 months vs. 8.5 months for those in partial remission, 21.0 months in those with stable disease, and 3.5 months for those with progressive disease at time of transplant, data show.

Patients with common PTCL subtypes had better PFS compared to patients with CTCL, yet OS was similar, according to the investigator. At 5 years, PFS was 43.7% and 18.6%, respectively, for PTCL and CTCL, while OS was 53.1% and 44.0%, respectively.

There was a trend toward improved outcomes for AITL relative to PTCL-NOS and ALCL, with a median PFS of 51.4 months for AITL versus 18.3 months those other subtypes. Similarly, median OS was not reached for AITL versus 73.1 months in the other subtypes.

Treatment-related mortality was lowest for patients with MRDs, or 8.2% at 12 months, Dr. Mehta-Shah reported, while patients with MUDs, mismatched donors, or haploidentical donors had treatment-related mortality of 13% to 16% at 12 months, and those with cord blood donors had treatment-related mortality of nearly 24% at 12 months.

Acute GvHD was observed in 46% of patients and chronic GvHD was seen in nearly 41%, the investigator added.

While these findings are important to consider in individual patient consultations, the study is nevertheless subject to limitations including patient selection and referral bias, according to Dr. Mehta-Shah.

“This was a retrospective analysis of patients who underwent transplant,” she said in a question-and-answer period. “Of course, that is heavily biased by who got to a transplant center, who was well enough to achieve transplant, and who had a donor or donor options, as well as their overall health and depth of remission,” the researcher said.

“I think this just represents what we could tell patients about what may happen to them once they embark on a transplant,” she added, “but really, there would be more prospective work needed to be done for what happens to patients overarching, and how many of them even get to a transplant consultation.”

Further studies should be done to develop predictive tools or biomarkers to determine who benefits from an allogeneic transplant, if there are predictors of relapse following allogeneic transplant, and what are the mechanisms of relapse following allogeneic transplant, according to Dr. Mehta-Shah.

Dr. Mehta-Shah reported research funding from Bristol Myers-Squibb, Celgene, Verastem, Corvus, Innate Pharmaceuticals, and Genentech/Roche. She reported consultancy with Kyowa Hakko Kirin, C4 Therapeutics, and Karyopharm Therapeutics.
 

SOURCE: Mehta-Shah N et al. ASH 2020, Abstract 41.

In patients with T-cell lymphoma, allogeneic transplant can lead to durable remissions among patients who might otherwise have poor outcomes, results of a large retrospective observational study suggest.

Five-year progression-free survival (PFS) approached 40% and 5-year overall survival (OS) was over 50% in the study, which according to an investigator is the largest-ever reported patient series of allogeneic stem cell transplantation in T-cell lymphomas.

“We believe that eligible patients with relapsed/refractory T-cell lymphomas should be considered for consultation for allogeneic transplant by an expert clinician,” said investigator Neha Mehta-Shah, MD, of Washington University in St. Louis.

“These decisions should occur on a patient by patient level – but it’s important to consider this,” Dr. Mehta-Shah said at the annual meeting of the American Society of Hematology, held virtually this year.

Notably, patients with cutaneous T-cell lymphoma (CTCL) had a higher rate of relapse yet similar overall survival (OS) compared to patients with common peripheral T-cell lymphoma (PTCL) subtypes, according to Dr. Mehta-Shah.

Among PTCL subtypes, there was a trend toward improved PFS and OS for angioimmunoblastic T-cell lymphoma (AITL), compared with PTCL not otherwise specified (PTCL-NOS) and anaplastic large-cell lymphoma (ALCL), she added.

Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone’s Perlmutter Cancer Center, said the results of this retrospective study need to considered in light of the treatment-related risks associated with allogeneic transplantation.

Treatment-related mortality in the study ranged from about 8% to 24%, depending on the donor type, while acute and chronic graft-versus-host-disease (GvHD) was seen in more than 40% of patients, the reported data show.

“If I have a relapsed patient with AITL, I would look to this data and say that patients with AITL appear in a retrospective study to have a strong benefit,” Dr. Diefenbach said in an interview.

“For the other patients, you would describe both potential benefits and also discuss the treatment-associated risks – both the chronic GvHD and transplant-related mortality – and you’d have to balance the risk with the benefits for each individual case,” Dr. Diefenbach added.

The retrospective analysis by Dr. Mehta-Shah and colleagues included 508 consecutive T-cell lymphoma patients receiving allogeneic transplants at 12 academic centers between 2000 and 2019. The most common subtypes were PTCL-NOS in 26%, AITL in 16%, CTCL in 13%, and hepatosplenic T-cell lymphoma (HSTCL) in 7%. About 40% had a matched related donor (MRD) and 39% had a matched unrelated donor (MUD). The conditioning regimen was myeloablative in about a third of patients and nonmyeloablative in two-thirds.

At 5 years, PFS was 39.4% and OS was 50.8% for the overall study cohort, Dr. Mehta-Shah reported, noting that the median time from relapse to death post allogeneic transplant was 10.2 months.

Patients in complete remission at the time of transplant fared better than others, with a median PFS of 44.6 months vs. 8.5 months for those in partial remission, 21.0 months in those with stable disease, and 3.5 months for those with progressive disease at time of transplant, data show.

Patients with common PTCL subtypes had better PFS compared to patients with CTCL, yet OS was similar, according to the investigator. At 5 years, PFS was 43.7% and 18.6%, respectively, for PTCL and CTCL, while OS was 53.1% and 44.0%, respectively.

There was a trend toward improved outcomes for AITL relative to PTCL-NOS and ALCL, with a median PFS of 51.4 months for AITL versus 18.3 months those other subtypes. Similarly, median OS was not reached for AITL versus 73.1 months in the other subtypes.

Treatment-related mortality was lowest for patients with MRDs, or 8.2% at 12 months, Dr. Mehta-Shah reported, while patients with MUDs, mismatched donors, or haploidentical donors had treatment-related mortality of 13% to 16% at 12 months, and those with cord blood donors had treatment-related mortality of nearly 24% at 12 months.

Acute GvHD was observed in 46% of patients and chronic GvHD was seen in nearly 41%, the investigator added.

While these findings are important to consider in individual patient consultations, the study is nevertheless subject to limitations including patient selection and referral bias, according to Dr. Mehta-Shah.

“This was a retrospective analysis of patients who underwent transplant,” she said in a question-and-answer period. “Of course, that is heavily biased by who got to a transplant center, who was well enough to achieve transplant, and who had a donor or donor options, as well as their overall health and depth of remission,” the researcher said.

“I think this just represents what we could tell patients about what may happen to them once they embark on a transplant,” she added, “but really, there would be more prospective work needed to be done for what happens to patients overarching, and how many of them even get to a transplant consultation.”

Further studies should be done to develop predictive tools or biomarkers to determine who benefits from an allogeneic transplant, if there are predictors of relapse following allogeneic transplant, and what are the mechanisms of relapse following allogeneic transplant, according to Dr. Mehta-Shah.

Dr. Mehta-Shah reported research funding from Bristol Myers-Squibb, Celgene, Verastem, Corvus, Innate Pharmaceuticals, and Genentech/Roche. She reported consultancy with Kyowa Hakko Kirin, C4 Therapeutics, and Karyopharm Therapeutics.
 

SOURCE: Mehta-Shah N et al. ASH 2020, Abstract 41.

Patients with hematologic disease who develop COVID-19 may experience substantial morbidity and mortality related to SARS-CoV-2 infection, according to recent registry data reported at the all-virtual annual meeting of the American Society of Hematology.

Overall mortality was 28% for the first 250 patients entered into the ASH Research Collaborative COVID-19 Registry for Hematology, researchers reported in an abstract of their study findings.

However, the burden of death and moderate-to-severe COVID-19 outcomes was highest in patients with poorer prognosis and those with relapsed/refractory hematological disease, they added.

The most commonly represented malignancies were acute leukemia, non-Hodgkin lymphoma, and myeloma or amyloidosis, according to the report.

Taken together, the findings do support an “emerging consensus” that COVID-19 related morbidity and mortality is significant in these patients, authors said – however, the current findings may not be reason enough to support a change in treatment course for the underlying disease.

“We see no reason, based on our data, to withhold intensive therapies from patients with underlying hematologic malignancies and favorable prognoses, if aggressive supportive care is consistent with patient preferences,” wrote the researchers.

ASH President Stephanie Lee, MD, MPH, said these registry findings are important to better understand how SARS-CoV-2 is affecting not only patients with hematologic diseases, but also individuals who experience COVID-19-related hematologic complications.

However, the findings are limited due to the heterogeneity of diseases, symptoms, and treatments represented in the registry, said Dr. Lee, associate director of the clinical research division at Fred Hutchinson Cancer Center in Seattle.

“More data will be coming in, but I think this is an example of trying to harness real-world information to try to learn things until we get more controlled studies,” Dr. Lee said in a media briefing held in advance of the ASH meeting.
 

Comorbidities and more

Patients with blood cancers are often older and may have comorbidities such as diabetes or hypertension that have been linked to poor COVID-19 outcomes, according to the authors of the report, led by William A. Wood, MD, MPH, associate professor of medicine with the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, N.C.

Moreover, these patients may have underlying immune dysfunction and may receive chemotherapy or immunotherapy that is “profoundly immunosuppressive,” Dr. Wood and coauthors said in their report.

To date, however, risks of morbidity and mortality related to SARS-CoV-2 infection have not been well defined in this patient population, authors said.

More data is emerging now from the ASH Research Collaborative COVID-19 Registry for Hematology, which includes data on patients positive for COVID-19 who have a past or present hematologic condition or have experienced a hematologic complication related to COVID-19.

All data from the registry is being made available through a dashboard on the ASH Research Collaborative website, which as of Dec. 1, 2020, included 693 complete cases.

The data cut in the ASH abstract includes the first 250 patients enrolled at 74 sites around the world, the authors said. The most common malignancies included acute leukemia in 33%, non-Hodgkin lymphoma in 27%, and myeloma or amyloidosis in 16%.

The most frequently reported symptoms included fever in 73%, cough in 67%, dyspnea in 50%, and fatigue in 40%, according to that report.

At the time of this data snapshot, treatment with COVID-19-directed therapies including hydroxychloroquine or azithromycin were common, reported in 76 and 59 patients, respectively, in the cohort.

Batch submissions from sites with high incidence of COVID-19 infection are ongoing. The registry has been expanded to include nonmalignant hematologic diseases, and the registry will continue to accumulate data as a resource for the hematology community.

Overall mortality was 28% at the time, according to the abstract, with nearly all of the deaths occurring in patients classified as having COVID-19 that was moderate (i.e., requiring hospitalization) or severe (i.e., requiring ICU admission).

“In some instances, death occurred after a decision was made to forgo ICU admission in favor of a palliative approach,” said Dr. Wood and coauthors in their report.

Dr. Wood reported research funding from Pfizer, consultancy with Teladoc/Best Doctors, and honoraria from the ASH Research Collaborative. Coauthors provided disclosures related to Celgene, Madrigal Pharmaceuticals, Pharmacyclics, and Amgen, among others.

SOURCE: Wood WA et al. ASH 2020, Abstract 215.

Patients with hematologic disease who develop COVID-19 may experience substantial morbidity and mortality related to SARS-CoV-2 infection, according to recent registry data reported at the all-virtual annual meeting of the American Society of Hematology.

Overall mortality was 28% for the first 250 patients entered into the ASH Research Collaborative COVID-19 Registry for Hematology, researchers reported in an abstract of their study findings.

However, the burden of death and moderate-to-severe COVID-19 outcomes was highest in patients with poorer prognosis and those with relapsed/refractory hematological disease, they added.

The most commonly represented malignancies were acute leukemia, non-Hodgkin lymphoma, and myeloma or amyloidosis, according to the report.

Taken together, the findings do support an “emerging consensus” that COVID-19 related morbidity and mortality is significant in these patients, authors said – however, the current findings may not be reason enough to support a change in treatment course for the underlying disease.

“We see no reason, based on our data, to withhold intensive therapies from patients with underlying hematologic malignancies and favorable prognoses, if aggressive supportive care is consistent with patient preferences,” wrote the researchers.

ASH President Stephanie Lee, MD, MPH, said these registry findings are important to better understand how SARS-CoV-2 is affecting not only patients with hematologic diseases, but also individuals who experience COVID-19-related hematologic complications.

However, the findings are limited due to the heterogeneity of diseases, symptoms, and treatments represented in the registry, said Dr. Lee, associate director of the clinical research division at Fred Hutchinson Cancer Center in Seattle.

“More data will be coming in, but I think this is an example of trying to harness real-world information to try to learn things until we get more controlled studies,” Dr. Lee said in a media briefing held in advance of the ASH meeting.
 

Comorbidities and more

Patients with blood cancers are often older and may have comorbidities such as diabetes or hypertension that have been linked to poor COVID-19 outcomes, according to the authors of the report, led by William A. Wood, MD, MPH, associate professor of medicine with the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, N.C.

Moreover, these patients may have underlying immune dysfunction and may receive chemotherapy or immunotherapy that is “profoundly immunosuppressive,” Dr. Wood and coauthors said in their report.

To date, however, risks of morbidity and mortality related to SARS-CoV-2 infection have not been well defined in this patient population, authors said.

More data is emerging now from the ASH Research Collaborative COVID-19 Registry for Hematology, which includes data on patients positive for COVID-19 who have a past or present hematologic condition or have experienced a hematologic complication related to COVID-19.

All data from the registry is being made available through a dashboard on the ASH Research Collaborative website, which as of Dec. 1, 2020, included 693 complete cases.

The data cut in the ASH abstract includes the first 250 patients enrolled at 74 sites around the world, the authors said. The most common malignancies included acute leukemia in 33%, non-Hodgkin lymphoma in 27%, and myeloma or amyloidosis in 16%.

The most frequently reported symptoms included fever in 73%, cough in 67%, dyspnea in 50%, and fatigue in 40%, according to that report.

At the time of this data snapshot, treatment with COVID-19-directed therapies including hydroxychloroquine or azithromycin were common, reported in 76 and 59 patients, respectively, in the cohort.

Batch submissions from sites with high incidence of COVID-19 infection are ongoing. The registry has been expanded to include nonmalignant hematologic diseases, and the registry will continue to accumulate data as a resource for the hematology community.

Overall mortality was 28% at the time, according to the abstract, with nearly all of the deaths occurring in patients classified as having COVID-19 that was moderate (i.e., requiring hospitalization) or severe (i.e., requiring ICU admission).

“In some instances, death occurred after a decision was made to forgo ICU admission in favor of a palliative approach,” said Dr. Wood and coauthors in their report.

Dr. Wood reported research funding from Pfizer, consultancy with Teladoc/Best Doctors, and honoraria from the ASH Research Collaborative. Coauthors provided disclosures related to Celgene, Madrigal Pharmaceuticals, Pharmacyclics, and Amgen, among others.

SOURCE: Wood WA et al. ASH 2020, Abstract 215.

Patients with hematologic disease who develop COVID-19 may experience substantial morbidity and mortality related to SARS-CoV-2 infection, according to recent registry data reported at the all-virtual annual meeting of the American Society of Hematology.

Overall mortality was 28% for the first 250 patients entered into the ASH Research Collaborative COVID-19 Registry for Hematology, researchers reported in an abstract of their study findings.

However, the burden of death and moderate-to-severe COVID-19 outcomes was highest in patients with poorer prognosis and those with relapsed/refractory hematological disease, they added.

The most commonly represented malignancies were acute leukemia, non-Hodgkin lymphoma, and myeloma or amyloidosis, according to the report.

Taken together, the findings do support an “emerging consensus” that COVID-19 related morbidity and mortality is significant in these patients, authors said – however, the current findings may not be reason enough to support a change in treatment course for the underlying disease.

“We see no reason, based on our data, to withhold intensive therapies from patients with underlying hematologic malignancies and favorable prognoses, if aggressive supportive care is consistent with patient preferences,” wrote the researchers.

ASH President Stephanie Lee, MD, MPH, said these registry findings are important to better understand how SARS-CoV-2 is affecting not only patients with hematologic diseases, but also individuals who experience COVID-19-related hematologic complications.

However, the findings are limited due to the heterogeneity of diseases, symptoms, and treatments represented in the registry, said Dr. Lee, associate director of the clinical research division at Fred Hutchinson Cancer Center in Seattle.

“More data will be coming in, but I think this is an example of trying to harness real-world information to try to learn things until we get more controlled studies,” Dr. Lee said in a media briefing held in advance of the ASH meeting.
 

Comorbidities and more

Patients with blood cancers are often older and may have comorbidities such as diabetes or hypertension that have been linked to poor COVID-19 outcomes, according to the authors of the report, led by William A. Wood, MD, MPH, associate professor of medicine with the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, N.C.

Moreover, these patients may have underlying immune dysfunction and may receive chemotherapy or immunotherapy that is “profoundly immunosuppressive,” Dr. Wood and coauthors said in their report.

To date, however, risks of morbidity and mortality related to SARS-CoV-2 infection have not been well defined in this patient population, authors said.

More data is emerging now from the ASH Research Collaborative COVID-19 Registry for Hematology, which includes data on patients positive for COVID-19 who have a past or present hematologic condition or have experienced a hematologic complication related to COVID-19.

All data from the registry is being made available through a dashboard on the ASH Research Collaborative website, which as of Dec. 1, 2020, included 693 complete cases.

The data cut in the ASH abstract includes the first 250 patients enrolled at 74 sites around the world, the authors said. The most common malignancies included acute leukemia in 33%, non-Hodgkin lymphoma in 27%, and myeloma or amyloidosis in 16%.

The most frequently reported symptoms included fever in 73%, cough in 67%, dyspnea in 50%, and fatigue in 40%, according to that report.

At the time of this data snapshot, treatment with COVID-19-directed therapies including hydroxychloroquine or azithromycin were common, reported in 76 and 59 patients, respectively, in the cohort.

Batch submissions from sites with high incidence of COVID-19 infection are ongoing. The registry has been expanded to include nonmalignant hematologic diseases, and the registry will continue to accumulate data as a resource for the hematology community.

Overall mortality was 28% at the time, according to the abstract, with nearly all of the deaths occurring in patients classified as having COVID-19 that was moderate (i.e., requiring hospitalization) or severe (i.e., requiring ICU admission).

“In some instances, death occurred after a decision was made to forgo ICU admission in favor of a palliative approach,” said Dr. Wood and coauthors in their report.

Dr. Wood reported research funding from Pfizer, consultancy with Teladoc/Best Doctors, and honoraria from the ASH Research Collaborative. Coauthors provided disclosures related to Celgene, Madrigal Pharmaceuticals, Pharmacyclics, and Amgen, among others.

SOURCE: Wood WA et al. ASH 2020, Abstract 215.

New guidelines recommend against retreatment with poly (ADP-ribose) polymerase (PARP) inhibitors in women with epithelial ovarian, tubal, or primary peritoneal cancer (EOC). However, trials investigating retreatment are underway, so this recommendation may change.

The guidelines, from the American Society of Clinical Oncology (ASCO), do not recommend PARP inhibitors for the initial treatment of stage I-II EOC.

However, PARP inhibitor maintenance should be offered to women with newly diagnosed stage III-IV EOC who achieved a complete or partial response with first-line platinum-based chemotherapy, according to the guidelines. Niraparib can be offered to all women meeting those criteria, while olaparib can be considered for patients with mutations in BRCA1/2.

The guidelines, published in the Journal of Clinical Oncology, are based on a systematic review of recent randomized PARP inhibitor trials, including PRIMA and SOLO1, among others.

What’s not available now is overall survival results from key clinical trials, the guideline authors noted. They added that further research is needed to address the issue of conserving platinum sensitivity in patients with disease progression on or after PARP inhibitor maintenance.

“Given the expectation that early treatment may confer the best outcome, maintenance therapy with PARP inhibitors should be offered, with these caveats,” the authors wrote.

Olaparib can also be added to bevacizumab maintenance therapy following response to first-line chemotherapy plus bevacizumab, according to the guidelines, which also address PARP inhibitor use for women with recurrent EOC, as well as management of adverse events.

The guidelines recommend against pairing PARP inhibitors with chemotherapy, targeted therapy, or immunotherapy outside a clinical trial.
 

Which drug, which setting, which dose?

This new ASCO guidelines may help cut through the complexity of treatment decision-making for women with EOC, according to Roisin E. O’Cearbhaill, MD, of Memorial Sloan Kettering Cancer Center in New York.

“Today as clinicians, we have a whole range of opportunities to give our patients PARP inhibitors in the upfront and recurrent setting,” Dr. O’Cearbhaill said in an interview. “It is quite complicated to know which PARP inhibitor should be used in which setting and which patients.”

“We want to make sure that patients who would derive the most benefit from PARP inhibitors are offered these agents but also that we’re careful not to use PARP inhibitors in settings where there is little or no data,” added Dr. O’Cearbhaill, who was not involved in the drafting of the guidelines.

The ASCO guidelines provide a detailed review of 17 clinical trials to address key issues, including the histologic types of EOC and biomarker subsets for which PARP inhibitors are recommended in the newly diagnosed setting, as well as the settings, dose, and duration of treatment that are recommended for patients with recurrent EOC who have not yet received a PARP inhibitor.

While PARP inhibitors are generally well tolerated, some characteristic toxicities – such as anemia, neutropenia, thrombocytopenia, persistent cytopenias, and nausea – may warrant dose reductions, the guidelines state.

Special attention must be paid to low-grade adverse events since PARP inhibitors are administered continuously on a daily basis, according to the guidelines. If a dose is held because of a grade 2 adverse event, the subsequent dose should be reduced to avoid a second dose hold.

“Reescalation or resumption of the initial dose is never recommended,” the guidelines state.
 

Retreatment

Dr. O’Cearbhaill said she is eager to see future guidelines addressing PARP inhibitor retreatment following disease progression, especially since more and more patients will receive these agents in the upfront setting.

Right now, there is little data available to address PARP inhibitor retreatment. However, the ASCO guidelines do mention the ongoing OReO/ENGOT OV-38 phase 3 trial of maintenance retreatment with olaparib in women with EOC.

This study, which includes patients who previously received a PARP inhibitor and who are responding to additional platinum-based chemotherapy, has an estimated completion date in May 2021, according to details on ClinicalTrials.gov.

That’s one of several trials designed to determine how best to incorporate PARP inhibitor retreatment into the treatment paradigm, according to Dr. O’Cearbhaill.

“Even if a high proportion of patients aren’t ultimately cured by this approach, if we can delay progression of disease by the order of months or even years, whilst proactively managing side effects, it would make such a big difference for patients,” she said. “It allows them to have a better quality of life and go about their daily activities without symptomatic ovarian cancer.”

Cochairs of the ASCO expert panel for the guidelines were William P. Tew, MD, of Memorial Sloan Kettering Cancer Center in New York, and Elise C. Kohn, MD, of the National Cancer Institute in Bethesda, Md. Dr. Tew and Dr. Kohn provided no disclosures, while their coauthors reported disclosures related to Roche, AstraZeneca, Tesaro, Clovis Oncology, Merck, Seattle Genetics, and other companies. Dr. O’Cearbhaill disclosed that she is a coauthor on the PRIMA/ENGOT-OV26/GOG-3012 phase 3 clinical trial (NCT02655016) and serves on the steering committee for DUO-O (NCT0373643). She reported personal fees from Clovis, Tesaro, Regeneron, and GlaxoSmithKline.

SOURCE: Tew WP et al. J Clin Oncol. 2020 Aug 13. doi: 10.1200/JCO.20.01924.

New guidelines recommend against retreatment with poly (ADP-ribose) polymerase (PARP) inhibitors in women with epithelial ovarian, tubal, or primary peritoneal cancer (EOC). However, trials investigating retreatment are underway, so this recommendation may change.

The guidelines, from the American Society of Clinical Oncology (ASCO), do not recommend PARP inhibitors for the initial treatment of stage I-II EOC.

However, PARP inhibitor maintenance should be offered to women with newly diagnosed stage III-IV EOC who achieved a complete or partial response with first-line platinum-based chemotherapy, according to the guidelines. Niraparib can be offered to all women meeting those criteria, while olaparib can be considered for patients with mutations in BRCA1/2.

The guidelines, published in the Journal of Clinical Oncology, are based on a systematic review of recent randomized PARP inhibitor trials, including PRIMA and SOLO1, among others.

What’s not available now is overall survival results from key clinical trials, the guideline authors noted. They added that further research is needed to address the issue of conserving platinum sensitivity in patients with disease progression on or after PARP inhibitor maintenance.

“Given the expectation that early treatment may confer the best outcome, maintenance therapy with PARP inhibitors should be offered, with these caveats,” the authors wrote.

Olaparib can also be added to bevacizumab maintenance therapy following response to first-line chemotherapy plus bevacizumab, according to the guidelines, which also address PARP inhibitor use for women with recurrent EOC, as well as management of adverse events.

The guidelines recommend against pairing PARP inhibitors with chemotherapy, targeted therapy, or immunotherapy outside a clinical trial.
 

Which drug, which setting, which dose?

This new ASCO guidelines may help cut through the complexity of treatment decision-making for women with EOC, according to Roisin E. O’Cearbhaill, MD, of Memorial Sloan Kettering Cancer Center in New York.

“Today as clinicians, we have a whole range of opportunities to give our patients PARP inhibitors in the upfront and recurrent setting,” Dr. O’Cearbhaill said in an interview. “It is quite complicated to know which PARP inhibitor should be used in which setting and which patients.”

“We want to make sure that patients who would derive the most benefit from PARP inhibitors are offered these agents but also that we’re careful not to use PARP inhibitors in settings where there is little or no data,” added Dr. O’Cearbhaill, who was not involved in the drafting of the guidelines.

The ASCO guidelines provide a detailed review of 17 clinical trials to address key issues, including the histologic types of EOC and biomarker subsets for which PARP inhibitors are recommended in the newly diagnosed setting, as well as the settings, dose, and duration of treatment that are recommended for patients with recurrent EOC who have not yet received a PARP inhibitor.

While PARP inhibitors are generally well tolerated, some characteristic toxicities – such as anemia, neutropenia, thrombocytopenia, persistent cytopenias, and nausea – may warrant dose reductions, the guidelines state.

Special attention must be paid to low-grade adverse events since PARP inhibitors are administered continuously on a daily basis, according to the guidelines. If a dose is held because of a grade 2 adverse event, the subsequent dose should be reduced to avoid a second dose hold.

“Reescalation or resumption of the initial dose is never recommended,” the guidelines state.
 

Retreatment

Dr. O’Cearbhaill said she is eager to see future guidelines addressing PARP inhibitor retreatment following disease progression, especially since more and more patients will receive these agents in the upfront setting.

Right now, there is little data available to address PARP inhibitor retreatment. However, the ASCO guidelines do mention the ongoing OReO/ENGOT OV-38 phase 3 trial of maintenance retreatment with olaparib in women with EOC.

This study, which includes patients who previously received a PARP inhibitor and who are responding to additional platinum-based chemotherapy, has an estimated completion date in May 2021, according to details on ClinicalTrials.gov.

That’s one of several trials designed to determine how best to incorporate PARP inhibitor retreatment into the treatment paradigm, according to Dr. O’Cearbhaill.

“Even if a high proportion of patients aren’t ultimately cured by this approach, if we can delay progression of disease by the order of months or even years, whilst proactively managing side effects, it would make such a big difference for patients,” she said. “It allows them to have a better quality of life and go about their daily activities without symptomatic ovarian cancer.”

Cochairs of the ASCO expert panel for the guidelines were William P. Tew, MD, of Memorial Sloan Kettering Cancer Center in New York, and Elise C. Kohn, MD, of the National Cancer Institute in Bethesda, Md. Dr. Tew and Dr. Kohn provided no disclosures, while their coauthors reported disclosures related to Roche, AstraZeneca, Tesaro, Clovis Oncology, Merck, Seattle Genetics, and other companies. Dr. O’Cearbhaill disclosed that she is a coauthor on the PRIMA/ENGOT-OV26/GOG-3012 phase 3 clinical trial (NCT02655016) and serves on the steering committee for DUO-O (NCT0373643). She reported personal fees from Clovis, Tesaro, Regeneron, and GlaxoSmithKline.

SOURCE: Tew WP et al. J Clin Oncol. 2020 Aug 13. doi: 10.1200/JCO.20.01924.

New guidelines recommend against retreatment with poly (ADP-ribose) polymerase (PARP) inhibitors in women with epithelial ovarian, tubal, or primary peritoneal cancer (EOC). However, trials investigating retreatment are underway, so this recommendation may change.

The guidelines, from the American Society of Clinical Oncology (ASCO), do not recommend PARP inhibitors for the initial treatment of stage I-II EOC.

However, PARP inhibitor maintenance should be offered to women with newly diagnosed stage III-IV EOC who achieved a complete or partial response with first-line platinum-based chemotherapy, according to the guidelines. Niraparib can be offered to all women meeting those criteria, while olaparib can be considered for patients with mutations in BRCA1/2.

The guidelines, published in the Journal of Clinical Oncology, are based on a systematic review of recent randomized PARP inhibitor trials, including PRIMA and SOLO1, among others.

What’s not available now is overall survival results from key clinical trials, the guideline authors noted. They added that further research is needed to address the issue of conserving platinum sensitivity in patients with disease progression on or after PARP inhibitor maintenance.

“Given the expectation that early treatment may confer the best outcome, maintenance therapy with PARP inhibitors should be offered, with these caveats,” the authors wrote.

Olaparib can also be added to bevacizumab maintenance therapy following response to first-line chemotherapy plus bevacizumab, according to the guidelines, which also address PARP inhibitor use for women with recurrent EOC, as well as management of adverse events.

The guidelines recommend against pairing PARP inhibitors with chemotherapy, targeted therapy, or immunotherapy outside a clinical trial.
 

Which drug, which setting, which dose?

This new ASCO guidelines may help cut through the complexity of treatment decision-making for women with EOC, according to Roisin E. O’Cearbhaill, MD, of Memorial Sloan Kettering Cancer Center in New York.

“Today as clinicians, we have a whole range of opportunities to give our patients PARP inhibitors in the upfront and recurrent setting,” Dr. O’Cearbhaill said in an interview. “It is quite complicated to know which PARP inhibitor should be used in which setting and which patients.”

“We want to make sure that patients who would derive the most benefit from PARP inhibitors are offered these agents but also that we’re careful not to use PARP inhibitors in settings where there is little or no data,” added Dr. O’Cearbhaill, who was not involved in the drafting of the guidelines.

The ASCO guidelines provide a detailed review of 17 clinical trials to address key issues, including the histologic types of EOC and biomarker subsets for which PARP inhibitors are recommended in the newly diagnosed setting, as well as the settings, dose, and duration of treatment that are recommended for patients with recurrent EOC who have not yet received a PARP inhibitor.

While PARP inhibitors are generally well tolerated, some characteristic toxicities – such as anemia, neutropenia, thrombocytopenia, persistent cytopenias, and nausea – may warrant dose reductions, the guidelines state.

Special attention must be paid to low-grade adverse events since PARP inhibitors are administered continuously on a daily basis, according to the guidelines. If a dose is held because of a grade 2 adverse event, the subsequent dose should be reduced to avoid a second dose hold.

“Reescalation or resumption of the initial dose is never recommended,” the guidelines state.
 

Retreatment

Dr. O’Cearbhaill said she is eager to see future guidelines addressing PARP inhibitor retreatment following disease progression, especially since more and more patients will receive these agents in the upfront setting.

Right now, there is little data available to address PARP inhibitor retreatment. However, the ASCO guidelines do mention the ongoing OReO/ENGOT OV-38 phase 3 trial of maintenance retreatment with olaparib in women with EOC.

This study, which includes patients who previously received a PARP inhibitor and who are responding to additional platinum-based chemotherapy, has an estimated completion date in May 2021, according to details on ClinicalTrials.gov.

That’s one of several trials designed to determine how best to incorporate PARP inhibitor retreatment into the treatment paradigm, according to Dr. O’Cearbhaill.

“Even if a high proportion of patients aren’t ultimately cured by this approach, if we can delay progression of disease by the order of months or even years, whilst proactively managing side effects, it would make such a big difference for patients,” she said. “It allows them to have a better quality of life and go about their daily activities without symptomatic ovarian cancer.”

Cochairs of the ASCO expert panel for the guidelines were William P. Tew, MD, of Memorial Sloan Kettering Cancer Center in New York, and Elise C. Kohn, MD, of the National Cancer Institute in Bethesda, Md. Dr. Tew and Dr. Kohn provided no disclosures, while their coauthors reported disclosures related to Roche, AstraZeneca, Tesaro, Clovis Oncology, Merck, Seattle Genetics, and other companies. Dr. O’Cearbhaill disclosed that she is a coauthor on the PRIMA/ENGOT-OV26/GOG-3012 phase 3 clinical trial (NCT02655016) and serves on the steering committee for DUO-O (NCT0373643). She reported personal fees from Clovis, Tesaro, Regeneron, and GlaxoSmithKline.

SOURCE: Tew WP et al. J Clin Oncol. 2020 Aug 13. doi: 10.1200/JCO.20.01924.

Obstructive sleep apnea diagnoses may not be carried over to the inpatient setting, with potentially negative consequences for clinical outcomes, quality of life, and health care costs, an investigator said at the virtual meeting of the American College of Chest Physicians.

In a retrospective, single-center study, nearly 40% of patients with obstructive sleep apnea (OSA) diagnosed in the outpatient setting did not have a corresponding diagnosis during hospitalization, according to researcher Nitasa Sahu, MD.*

The missed OSA diagnoses could have especially negative implications for patients who don’t continue on positive airway pressure (PAP) therapy during the hospital stay, said Dr. Sahu, a fellow in pulmonary/critical care at St. Luke’s University Health Network in Bethlehem, Pa.

The finding indicates a large-magnitude opportunity to improve health care through better communication and optimized care, according to the researcher.

“Obstructive sleep apnea is underrecognized, it’s underdiagnosed, and it has a lot of implications for a patient’s hospitalization,” she said in interview

Clinical pathways should be set up to ensure that patients with OSA are properly identified and use their prescribed treatment, according to Dr. Sahu.

“I think that should, and would, reduce overall health care costs, with better outcomes as well,” she said.

Pulmonologist Saadia A. Faiz, MD, FCCP, said she hoped this study, presented at a late-breaking abstract at the virtual meeting, would highlight the importance of OSA screening and call attention to barriers to screening that may be in place in the inpatient setting.

That’s especially important because, after admission, the focus is often on the cause of admission rather than underlying comorbidities such as OSA, said Dr. Faiz, professor in the department of pulmonary medicine at the University of Texas MD Anderson Cancer Center in Houston.

“Working in a cancer hospital, the focus is always on the cancer, so sometimes even the patient will dismiss issues with their sleep,” Dr. Faiz said of her own experience in an interview.

“Often with sleep apnea, for people in the general population, the reason they seek medical attention is because their spouse notices that they’re snoring, so it is something that is not as emphasized,” added Dr. Faiz, who was not involved in the study.

In their study, Dr. Sahu and coauthors reviewed electronic health record data for adults hospitalized on the general internal medicine service at Penn State Hershey Medical Center from January 2017 through 2018. They restricted their search to first admissions.

The researchers looked for ICD-9 codes indicating an OSA diagnosis during their inpatient admission. They looked for the same codes in the preceding 5 years to see if the patients had a prior outpatient OSA diagnosis.

The inpatient cohort included 13,067 patients, of whom 53% were male, 87% were White, and 77% were over 50 years of age. Comorbidities included hypertension in 42%, atrial fibrillation in 21%, type 2 diabetes mellitus in 14%, congestive heart failure in 15%, and prior stroke in 0.5%.

A total of 991 individuals in the inpatient cohort had a prior outpatient OSA diagnosis. Of that group, 376 patients (38%) did not have an inpatient OSA diagnosis on inpatient record, according to the reported study data.

That large proportion of discordant diagnoses suggests a lot of missed opportunities to provide OSA therapy in the inpatient setting and to reinforce chronic disease state management, according to Dr. Sahu and colleagues.

How those discordant OSA diagnoses impact length of stay, cost of care, and readmissions are unanswered questions that deserve further study, Dr. Sahu said.

Among patients who did not have outpatient OSA diagnoses, another 804 patients, or about 6%, ended up with an inpatient diagnosis during their hospitalization, the researchers also reported.

While a number of those inpatient OSA diagnoses could have been coded in error, it’s also possible that they were indeed cases of OSA that went unrecognized until the individuals were hospitalized, Dr. Sahu said.

Dr. Sahu had no relevant relationships to report related to the study. One of four study coauthors reported relationships with Boehringer-Ingelheim, Nitto Denko, and Galapagos.

SOURCE: Sahu N. CHEST 2020. Abstract.

*Correction, 11/3/20: An earlier version of this article misstated the name of Nitasa Sahu, MD.

Obstructive sleep apnea diagnoses may not be carried over to the inpatient setting, with potentially negative consequences for clinical outcomes, quality of life, and health care costs, an investigator said at the virtual meeting of the American College of Chest Physicians.

In a retrospective, single-center study, nearly 40% of patients with obstructive sleep apnea (OSA) diagnosed in the outpatient setting did not have a corresponding diagnosis during hospitalization, according to researcher Nitasa Sahu, MD.*

The missed OSA diagnoses could have especially negative implications for patients who don’t continue on positive airway pressure (PAP) therapy during the hospital stay, said Dr. Sahu, a fellow in pulmonary/critical care at St. Luke’s University Health Network in Bethlehem, Pa.

The finding indicates a large-magnitude opportunity to improve health care through better communication and optimized care, according to the researcher.

“Obstructive sleep apnea is underrecognized, it’s underdiagnosed, and it has a lot of implications for a patient’s hospitalization,” she said in interview

Clinical pathways should be set up to ensure that patients with OSA are properly identified and use their prescribed treatment, according to Dr. Sahu.

“I think that should, and would, reduce overall health care costs, with better outcomes as well,” she said.

Pulmonologist Saadia A. Faiz, MD, FCCP, said she hoped this study, presented at a late-breaking abstract at the virtual meeting, would highlight the importance of OSA screening and call attention to barriers to screening that may be in place in the inpatient setting.

That’s especially important because, after admission, the focus is often on the cause of admission rather than underlying comorbidities such as OSA, said Dr. Faiz, professor in the department of pulmonary medicine at the University of Texas MD Anderson Cancer Center in Houston.

“Working in a cancer hospital, the focus is always on the cancer, so sometimes even the patient will dismiss issues with their sleep,” Dr. Faiz said of her own experience in an interview.

“Often with sleep apnea, for people in the general population, the reason they seek medical attention is because their spouse notices that they’re snoring, so it is something that is not as emphasized,” added Dr. Faiz, who was not involved in the study.

In their study, Dr. Sahu and coauthors reviewed electronic health record data for adults hospitalized on the general internal medicine service at Penn State Hershey Medical Center from January 2017 through 2018. They restricted their search to first admissions.

The researchers looked for ICD-9 codes indicating an OSA diagnosis during their inpatient admission. They looked for the same codes in the preceding 5 years to see if the patients had a prior outpatient OSA diagnosis.

The inpatient cohort included 13,067 patients, of whom 53% were male, 87% were White, and 77% were over 50 years of age. Comorbidities included hypertension in 42%, atrial fibrillation in 21%, type 2 diabetes mellitus in 14%, congestive heart failure in 15%, and prior stroke in 0.5%.

A total of 991 individuals in the inpatient cohort had a prior outpatient OSA diagnosis. Of that group, 376 patients (38%) did not have an inpatient OSA diagnosis on inpatient record, according to the reported study data.

That large proportion of discordant diagnoses suggests a lot of missed opportunities to provide OSA therapy in the inpatient setting and to reinforce chronic disease state management, according to Dr. Sahu and colleagues.

How those discordant OSA diagnoses impact length of stay, cost of care, and readmissions are unanswered questions that deserve further study, Dr. Sahu said.

Among patients who did not have outpatient OSA diagnoses, another 804 patients, or about 6%, ended up with an inpatient diagnosis during their hospitalization, the researchers also reported.

While a number of those inpatient OSA diagnoses could have been coded in error, it’s also possible that they were indeed cases of OSA that went unrecognized until the individuals were hospitalized, Dr. Sahu said.

Dr. Sahu had no relevant relationships to report related to the study. One of four study coauthors reported relationships with Boehringer-Ingelheim, Nitto Denko, and Galapagos.

SOURCE: Sahu N. CHEST 2020. Abstract.

*Correction, 11/3/20: An earlier version of this article misstated the name of Nitasa Sahu, MD.

Obstructive sleep apnea diagnoses may not be carried over to the inpatient setting, with potentially negative consequences for clinical outcomes, quality of life, and health care costs, an investigator said at the virtual meeting of the American College of Chest Physicians.

In a retrospective, single-center study, nearly 40% of patients with obstructive sleep apnea (OSA) diagnosed in the outpatient setting did not have a corresponding diagnosis during hospitalization, according to researcher Nitasa Sahu, MD.*

The missed OSA diagnoses could have especially negative implications for patients who don’t continue on positive airway pressure (PAP) therapy during the hospital stay, said Dr. Sahu, a fellow in pulmonary/critical care at St. Luke’s University Health Network in Bethlehem, Pa.

The finding indicates a large-magnitude opportunity to improve health care through better communication and optimized care, according to the researcher.

“Obstructive sleep apnea is underrecognized, it’s underdiagnosed, and it has a lot of implications for a patient’s hospitalization,” she said in interview

Clinical pathways should be set up to ensure that patients with OSA are properly identified and use their prescribed treatment, according to Dr. Sahu.

“I think that should, and would, reduce overall health care costs, with better outcomes as well,” she said.

Pulmonologist Saadia A. Faiz, MD, FCCP, said she hoped this study, presented at a late-breaking abstract at the virtual meeting, would highlight the importance of OSA screening and call attention to barriers to screening that may be in place in the inpatient setting.

That’s especially important because, after admission, the focus is often on the cause of admission rather than underlying comorbidities such as OSA, said Dr. Faiz, professor in the department of pulmonary medicine at the University of Texas MD Anderson Cancer Center in Houston.

“Working in a cancer hospital, the focus is always on the cancer, so sometimes even the patient will dismiss issues with their sleep,” Dr. Faiz said of her own experience in an interview.

“Often with sleep apnea, for people in the general population, the reason they seek medical attention is because their spouse notices that they’re snoring, so it is something that is not as emphasized,” added Dr. Faiz, who was not involved in the study.

In their study, Dr. Sahu and coauthors reviewed electronic health record data for adults hospitalized on the general internal medicine service at Penn State Hershey Medical Center from January 2017 through 2018. They restricted their search to first admissions.

The researchers looked for ICD-9 codes indicating an OSA diagnosis during their inpatient admission. They looked for the same codes in the preceding 5 years to see if the patients had a prior outpatient OSA diagnosis.

The inpatient cohort included 13,067 patients, of whom 53% were male, 87% were White, and 77% were over 50 years of age. Comorbidities included hypertension in 42%, atrial fibrillation in 21%, type 2 diabetes mellitus in 14%, congestive heart failure in 15%, and prior stroke in 0.5%.

A total of 991 individuals in the inpatient cohort had a prior outpatient OSA diagnosis. Of that group, 376 patients (38%) did not have an inpatient OSA diagnosis on inpatient record, according to the reported study data.

That large proportion of discordant diagnoses suggests a lot of missed opportunities to provide OSA therapy in the inpatient setting and to reinforce chronic disease state management, according to Dr. Sahu and colleagues.

How those discordant OSA diagnoses impact length of stay, cost of care, and readmissions are unanswered questions that deserve further study, Dr. Sahu said.

Among patients who did not have outpatient OSA diagnoses, another 804 patients, or about 6%, ended up with an inpatient diagnosis during their hospitalization, the researchers also reported.

While a number of those inpatient OSA diagnoses could have been coded in error, it’s also possible that they were indeed cases of OSA that went unrecognized until the individuals were hospitalized, Dr. Sahu said.

Dr. Sahu had no relevant relationships to report related to the study. One of four study coauthors reported relationships with Boehringer-Ingelheim, Nitto Denko, and Galapagos.

SOURCE: Sahu N. CHEST 2020. Abstract.

*Correction, 11/3/20: An earlier version of this article misstated the name of Nitasa Sahu, MD.

In patients with intermediate-risk pulmonary arterial hypertension (PAH) who are not at treatment goal on standard therapy, switching to riociguat is a promising strategy across a broad range of patient subgroups, an investigator said at the annual meeting of the American College of Chest Physicians, held virtually this year.

Patients switching to riociguat in the REPLACE study more frequently met the primary efficacy endpoint, compared with patients who remained on a phosphodiesterase-5 (PDE5) inhibitor, said Marius M. Hoeper, MD, of the Clinic for Respiratory Medicine at Hannover (Germany) Medical School.

That clinical benefit of switching to riociguat, a soluble guanylate cyclase (sGC) stimulator, was relatively consistent across patient subgroups including age, sex, PAH subtype, according to Dr. Hoeper.

“At the end of the day, we believe that switching from a PDE5 inhibitor to riociguat can benefit patients with PAH at intermediate risk and may serve as a new strategic option for treatment escalation,” he said in a live virtual presentation of the study results.

About 40% of patients switching to riociguat met the primary endpoint of clinical improvement in absence of clinical worsening versus just 20% of patients who stayed on a PDE5 inhibitor, according to top-line results of the phase 4 REPLACE study, which were reported Sept. 7 at the annual meeting of the European Respiratory Society.

Results of REPLACE presented at the CHEST meeting show a benefit across most patient subgroups, including PAH subtype and whether patients came from monotherapy or combination treatment to riociguat. Some groups did not appear to respond quite as well to switching, including elderly patients, patients with a 6-minute walk distance (6MWD) of less than 320 meters at baseline, and patients switching from tadalafil as opposed to sildenafil. However, these findings were not statistically significant and may have been chance findings, according to Dr. Hoeper.

These results of REPLACE suggest the efficacy of riociguat “across the board” for intermediate-risk PAH patients with inadequate response to standard therapy, said Vijay Balasubramanian, MD, FCCP, clinical professor of medicine at the University of California San Francisco, Fresno.

Based on REPLACE results, switching from a PDE5 inhibitor to riociguat is now a “strong potential option” beyond adding a third drug such as selexipag or an inhaled prostacyclin to usual treatment with a PDE5 inhibitor plus an endothelin receptor antagonist, Dr. Balasubramanian said in an interview.

“We now have an evidence-based option where you can stay on a two-drug regimen and see whether the switch would work just as well,” said Dr. Balasubramanian, vice chair of the Pulmonary Vascular Disease Steering Committee for the American College of Chest Physicians.

REPLACE is a randomized phase 4 study including 226 patients with PAH considered to be at intermediate risk according to World Health Organization functional class III or 6MWD of 165-440 meters. The composite primary endpoint was defined as no clinical worsening (death, disease progression, or hospitalization for worsening PAH) plus clinical improvement on at least two measures including an improvement in 6MWD, achieving WHO functional class I/II, or a decrease in N-terminal pro-brain natriuretic peptide (NT-proBNP).

The primary endpoint of REPLACE was met, showing that 45 patients (41%) who switched to riociguat had clinical improvement without clinical worsening versus 22 patient (20%) who stayed on the PDE5 inhibitor (odds ratio, 2.78; 95% confidence interval, 1.53-5.06; P = .0007), Dr. Hoeper reported.

The benefit appeared consistent across PAH subgroups, according to Dr. Hoeper. In patients with idiopathic, heritable, or drug- and toxin-induced PAH, the primary endpoint favored riociguat over PDE5 inhibitor, at 45% and 23%, respectively. Similarly, a higher proportion of patients with PAH associated with congenital heart disease or portal hypertension achieved the primary endpoint (46% vs. 8%), as did patients with PAH associated with connective tissue disease (25% vs. 16%).

Adverse events were seen in 71% of riociguat-treated patients and 66% of PDE5 inhibitor–treated patients, according to Dr. Hoeper, who said severe adverse events were more frequent with PDE5-inhibitor treatment, at 17% versus 7% for riociguat. There were three clinical worsening events in the PDE5 inhibitor group leading to death, while a fourth patient died in safety follow-up, according to the reported results, whereas there were no deaths reported with riociguat.

The REPLACE study was cofunded by Bayer AG and Merck Sharpe & Dohme, a subsidiary of Merck & Co. Dr. Hoeper reported receiving fees for consultations or lectures from Acceleron, Actelion, Bayer AG, Janssen, MSD, and Pfizer.

SOURCE: Hoeper MM. CHEST 2020, Abstract A2156-A2159.

In patients with intermediate-risk pulmonary arterial hypertension (PAH) who are not at treatment goal on standard therapy, switching to riociguat is a promising strategy across a broad range of patient subgroups, an investigator said at the annual meeting of the American College of Chest Physicians, held virtually this year.

Patients switching to riociguat in the REPLACE study more frequently met the primary efficacy endpoint, compared with patients who remained on a phosphodiesterase-5 (PDE5) inhibitor, said Marius M. Hoeper, MD, of the Clinic for Respiratory Medicine at Hannover (Germany) Medical School.

That clinical benefit of switching to riociguat, a soluble guanylate cyclase (sGC) stimulator, was relatively consistent across patient subgroups including age, sex, PAH subtype, according to Dr. Hoeper.

“At the end of the day, we believe that switching from a PDE5 inhibitor to riociguat can benefit patients with PAH at intermediate risk and may serve as a new strategic option for treatment escalation,” he said in a live virtual presentation of the study results.

About 40% of patients switching to riociguat met the primary endpoint of clinical improvement in absence of clinical worsening versus just 20% of patients who stayed on a PDE5 inhibitor, according to top-line results of the phase 4 REPLACE study, which were reported Sept. 7 at the annual meeting of the European Respiratory Society.

Results of REPLACE presented at the CHEST meeting show a benefit across most patient subgroups, including PAH subtype and whether patients came from monotherapy or combination treatment to riociguat. Some groups did not appear to respond quite as well to switching, including elderly patients, patients with a 6-minute walk distance (6MWD) of less than 320 meters at baseline, and patients switching from tadalafil as opposed to sildenafil. However, these findings were not statistically significant and may have been chance findings, according to Dr. Hoeper.

These results of REPLACE suggest the efficacy of riociguat “across the board” for intermediate-risk PAH patients with inadequate response to standard therapy, said Vijay Balasubramanian, MD, FCCP, clinical professor of medicine at the University of California San Francisco, Fresno.

Based on REPLACE results, switching from a PDE5 inhibitor to riociguat is now a “strong potential option” beyond adding a third drug such as selexipag or an inhaled prostacyclin to usual treatment with a PDE5 inhibitor plus an endothelin receptor antagonist, Dr. Balasubramanian said in an interview.

“We now have an evidence-based option where you can stay on a two-drug regimen and see whether the switch would work just as well,” said Dr. Balasubramanian, vice chair of the Pulmonary Vascular Disease Steering Committee for the American College of Chest Physicians.

REPLACE is a randomized phase 4 study including 226 patients with PAH considered to be at intermediate risk according to World Health Organization functional class III or 6MWD of 165-440 meters. The composite primary endpoint was defined as no clinical worsening (death, disease progression, or hospitalization for worsening PAH) plus clinical improvement on at least two measures including an improvement in 6MWD, achieving WHO functional class I/II, or a decrease in N-terminal pro-brain natriuretic peptide (NT-proBNP).

The primary endpoint of REPLACE was met, showing that 45 patients (41%) who switched to riociguat had clinical improvement without clinical worsening versus 22 patient (20%) who stayed on the PDE5 inhibitor (odds ratio, 2.78; 95% confidence interval, 1.53-5.06; P = .0007), Dr. Hoeper reported.

The benefit appeared consistent across PAH subgroups, according to Dr. Hoeper. In patients with idiopathic, heritable, or drug- and toxin-induced PAH, the primary endpoint favored riociguat over PDE5 inhibitor, at 45% and 23%, respectively. Similarly, a higher proportion of patients with PAH associated with congenital heart disease or portal hypertension achieved the primary endpoint (46% vs. 8%), as did patients with PAH associated with connective tissue disease (25% vs. 16%).

Adverse events were seen in 71% of riociguat-treated patients and 66% of PDE5 inhibitor–treated patients, according to Dr. Hoeper, who said severe adverse events were more frequent with PDE5-inhibitor treatment, at 17% versus 7% for riociguat. There were three clinical worsening events in the PDE5 inhibitor group leading to death, while a fourth patient died in safety follow-up, according to the reported results, whereas there were no deaths reported with riociguat.

The REPLACE study was cofunded by Bayer AG and Merck Sharpe & Dohme, a subsidiary of Merck & Co. Dr. Hoeper reported receiving fees for consultations or lectures from Acceleron, Actelion, Bayer AG, Janssen, MSD, and Pfizer.

SOURCE: Hoeper MM. CHEST 2020, Abstract A2156-A2159.

In patients with intermediate-risk pulmonary arterial hypertension (PAH) who are not at treatment goal on standard therapy, switching to riociguat is a promising strategy across a broad range of patient subgroups, an investigator said at the annual meeting of the American College of Chest Physicians, held virtually this year.

Patients switching to riociguat in the REPLACE study more frequently met the primary efficacy endpoint, compared with patients who remained on a phosphodiesterase-5 (PDE5) inhibitor, said Marius M. Hoeper, MD, of the Clinic for Respiratory Medicine at Hannover (Germany) Medical School.

That clinical benefit of switching to riociguat, a soluble guanylate cyclase (sGC) stimulator, was relatively consistent across patient subgroups including age, sex, PAH subtype, according to Dr. Hoeper.

“At the end of the day, we believe that switching from a PDE5 inhibitor to riociguat can benefit patients with PAH at intermediate risk and may serve as a new strategic option for treatment escalation,” he said in a live virtual presentation of the study results.

About 40% of patients switching to riociguat met the primary endpoint of clinical improvement in absence of clinical worsening versus just 20% of patients who stayed on a PDE5 inhibitor, according to top-line results of the phase 4 REPLACE study, which were reported Sept. 7 at the annual meeting of the European Respiratory Society.

Results of REPLACE presented at the CHEST meeting show a benefit across most patient subgroups, including PAH subtype and whether patients came from monotherapy or combination treatment to riociguat. Some groups did not appear to respond quite as well to switching, including elderly patients, patients with a 6-minute walk distance (6MWD) of less than 320 meters at baseline, and patients switching from tadalafil as opposed to sildenafil. However, these findings were not statistically significant and may have been chance findings, according to Dr. Hoeper.

These results of REPLACE suggest the efficacy of riociguat “across the board” for intermediate-risk PAH patients with inadequate response to standard therapy, said Vijay Balasubramanian, MD, FCCP, clinical professor of medicine at the University of California San Francisco, Fresno.

Based on REPLACE results, switching from a PDE5 inhibitor to riociguat is now a “strong potential option” beyond adding a third drug such as selexipag or an inhaled prostacyclin to usual treatment with a PDE5 inhibitor plus an endothelin receptor antagonist, Dr. Balasubramanian said in an interview.

“We now have an evidence-based option where you can stay on a two-drug regimen and see whether the switch would work just as well,” said Dr. Balasubramanian, vice chair of the Pulmonary Vascular Disease Steering Committee for the American College of Chest Physicians.

REPLACE is a randomized phase 4 study including 226 patients with PAH considered to be at intermediate risk according to World Health Organization functional class III or 6MWD of 165-440 meters. The composite primary endpoint was defined as no clinical worsening (death, disease progression, or hospitalization for worsening PAH) plus clinical improvement on at least two measures including an improvement in 6MWD, achieving WHO functional class I/II, or a decrease in N-terminal pro-brain natriuretic peptide (NT-proBNP).

The primary endpoint of REPLACE was met, showing that 45 patients (41%) who switched to riociguat had clinical improvement without clinical worsening versus 22 patient (20%) who stayed on the PDE5 inhibitor (odds ratio, 2.78; 95% confidence interval, 1.53-5.06; P = .0007), Dr. Hoeper reported.

The benefit appeared consistent across PAH subgroups, according to Dr. Hoeper. In patients with idiopathic, heritable, or drug- and toxin-induced PAH, the primary endpoint favored riociguat over PDE5 inhibitor, at 45% and 23%, respectively. Similarly, a higher proportion of patients with PAH associated with congenital heart disease or portal hypertension achieved the primary endpoint (46% vs. 8%), as did patients with PAH associated with connective tissue disease (25% vs. 16%).

Adverse events were seen in 71% of riociguat-treated patients and 66% of PDE5 inhibitor–treated patients, according to Dr. Hoeper, who said severe adverse events were more frequent with PDE5-inhibitor treatment, at 17% versus 7% for riociguat. There were three clinical worsening events in the PDE5 inhibitor group leading to death, while a fourth patient died in safety follow-up, according to the reported results, whereas there were no deaths reported with riociguat.

The REPLACE study was cofunded by Bayer AG and Merck Sharpe & Dohme, a subsidiary of Merck & Co. Dr. Hoeper reported receiving fees for consultations or lectures from Acceleron, Actelion, Bayer AG, Janssen, MSD, and Pfizer.

SOURCE: Hoeper MM. CHEST 2020, Abstract A2156-A2159.

Among individuals admitted to hospitals with sepsis, statin users had a lower mortality, compared with nonstatin users, according to a recent analysis focused on a large and diverse cohort of patients in California.

Mortality hazard ratios at 30 and 90 days were lower by about 20% for statin users admitted for sepsis, compared with nonstatin users, according to results of the retrospective cohort study.

Hydrophilic and synthetic statins had more favorable mortality outcomes, compared with lipophilic and fungal-derived statins, respectively, added investigator Brannen Liang, MD, a third-year internal medicine resident at Kaiser Permanente Los Angeles Medical Center.

These findings suggest a potential benefit of statins in patients with sepsis, with certain types of statins having a greater protective effect than others, according to Dr. Liang, who presented the original research in a presentation at the annual meeting of the American College of Chest Physicians, held virtually this year.

“I think there’s potential for extending the use of statins to other indications, such as sepsis,” Dr. Liang said in an interview, though he also cautioned that the present study is hypothesis generating and more research is necessary.

Using a certain statin type over another (i.e., a hydrophilic, synthetic statin) might be a consideration for populations who are at greater risk for sepsis, such as the immunocompromised, patients with diabetes, or elderly and who also require a statin for an indication such as hyperlipidemia, he added.

While the link between statin use and sepsis mortality outcomes is not new, this study is unique in that it replicates results of earlier studies in a large and diverse real-world population, Dr. Liang said.

“Numerous studies seem to suggest that statins may play a role in attenuating the mortality of patients admitted to the hospital with sepsis, for whatever reason – whether this is due to their anti-inflammatory effects, their lipid-lowering effects, or if they truly have an antimicrobial effect, which has been studied in vitro and in animal studies,” he said in an interview.

It’s impossible to definitively conclude from retrospective studies such as this whether statins reduce sepsis-related mortality risk, but the present study at least makes the case for using certain types of statins when they are indicated in high-risk patients, said Steven Q. Simpson, MD, FCCP, professor of medicine in the division of pulmonary and critical care medicine at the University of Kansas, Kansas City.

“If you have patients at high risk for sepsis and they need a statin, you could give consideration to using a hydrophilic and synthetic statin, rather than either of the other choices,” said Dr. Simpson, CHEST president-elect and senior advisor to the Solving Sepsis initiative of the Biomedical Advanced Research and Development Authority of the Department of Health & Human Services.

The retrospective cohort study by Dr. Liang and colleagues included a total of 137,019 individuals admitted for sepsis within the Kaiser Permanente Southern California health system between 2008 and 2018. Of that group, 36,908 were taking a statin.

Overall, the mean age of patients admitted for sepsis was 66.9 years, and 50.4% were female. Nearly 50% were White, about 12% were Black, 28% were Hispanic, and 8% were Asian. A diagnosis of ischemic heart disease was reported for 43% of statin users and 23% of nonusers, while diabetes mellitus was reported for 60% of statin users and 37% of nonusers (P < .0001 for both comparisons).

Differences in mortality favored statin users, compared with nonusers, with hazard ratios of 0.79 (95% confidence interval, 0.77-0.82) at 30 days and similarly, 0.79 (95% CI, 0.77-0.81) at 90 days, Dr. Liang reported, noting that the models were adjusted for age, race, sex, and comorbidities.

Further analysis suggested a mortality advantage of lipophilic, compared with hydrophilic statins, and an advantage of fungal-derived statins over synthetic-derived statins, the investigator added.

In the comparison of lipophilic statin users and hydrophilic statin users, the 30- and 90-day mortality HRs were 1.13 (95% CI, 1.02-1.26) and 1.17 (95% CI, 1.07-1.28), respectively, the data show. For fungal-derived statin users, compared with synthetic derived statin users, 30- and 90-day mortality HRs were 1.12 (95% CI, 1.06-1.19) and 1.14 (95% CI, 1.09-1.20), respectively.

Dr. Liang and coauthors disclosed no relevant relationships with respect to the work presented at the CHEST meeting.

SOURCE: Liang B et al. CHEST 2020, Abstract A589.

Among individuals admitted to hospitals with sepsis, statin users had a lower mortality, compared with nonstatin users, according to a recent analysis focused on a large and diverse cohort of patients in California.

Mortality hazard ratios at 30 and 90 days were lower by about 20% for statin users admitted for sepsis, compared with nonstatin users, according to results of the retrospective cohort study.

Hydrophilic and synthetic statins had more favorable mortality outcomes, compared with lipophilic and fungal-derived statins, respectively, added investigator Brannen Liang, MD, a third-year internal medicine resident at Kaiser Permanente Los Angeles Medical Center.

These findings suggest a potential benefit of statins in patients with sepsis, with certain types of statins having a greater protective effect than others, according to Dr. Liang, who presented the original research in a presentation at the annual meeting of the American College of Chest Physicians, held virtually this year.

“I think there’s potential for extending the use of statins to other indications, such as sepsis,” Dr. Liang said in an interview, though he also cautioned that the present study is hypothesis generating and more research is necessary.

Using a certain statin type over another (i.e., a hydrophilic, synthetic statin) might be a consideration for populations who are at greater risk for sepsis, such as the immunocompromised, patients with diabetes, or elderly and who also require a statin for an indication such as hyperlipidemia, he added.

While the link between statin use and sepsis mortality outcomes is not new, this study is unique in that it replicates results of earlier studies in a large and diverse real-world population, Dr. Liang said.

“Numerous studies seem to suggest that statins may play a role in attenuating the mortality of patients admitted to the hospital with sepsis, for whatever reason – whether this is due to their anti-inflammatory effects, their lipid-lowering effects, or if they truly have an antimicrobial effect, which has been studied in vitro and in animal studies,” he said in an interview.

It’s impossible to definitively conclude from retrospective studies such as this whether statins reduce sepsis-related mortality risk, but the present study at least makes the case for using certain types of statins when they are indicated in high-risk patients, said Steven Q. Simpson, MD, FCCP, professor of medicine in the division of pulmonary and critical care medicine at the University of Kansas, Kansas City.

“If you have patients at high risk for sepsis and they need a statin, you could give consideration to using a hydrophilic and synthetic statin, rather than either of the other choices,” said Dr. Simpson, CHEST president-elect and senior advisor to the Solving Sepsis initiative of the Biomedical Advanced Research and Development Authority of the Department of Health & Human Services.

The retrospective cohort study by Dr. Liang and colleagues included a total of 137,019 individuals admitted for sepsis within the Kaiser Permanente Southern California health system between 2008 and 2018. Of that group, 36,908 were taking a statin.

Overall, the mean age of patients admitted for sepsis was 66.9 years, and 50.4% were female. Nearly 50% were White, about 12% were Black, 28% were Hispanic, and 8% were Asian. A diagnosis of ischemic heart disease was reported for 43% of statin users and 23% of nonusers, while diabetes mellitus was reported for 60% of statin users and 37% of nonusers (P < .0001 for both comparisons).

Differences in mortality favored statin users, compared with nonusers, with hazard ratios of 0.79 (95% confidence interval, 0.77-0.82) at 30 days and similarly, 0.79 (95% CI, 0.77-0.81) at 90 days, Dr. Liang reported, noting that the models were adjusted for age, race, sex, and comorbidities.

Further analysis suggested a mortality advantage of lipophilic, compared with hydrophilic statins, and an advantage of fungal-derived statins over synthetic-derived statins, the investigator added.

In the comparison of lipophilic statin users and hydrophilic statin users, the 30- and 90-day mortality HRs were 1.13 (95% CI, 1.02-1.26) and 1.17 (95% CI, 1.07-1.28), respectively, the data show. For fungal-derived statin users, compared with synthetic derived statin users, 30- and 90-day mortality HRs were 1.12 (95% CI, 1.06-1.19) and 1.14 (95% CI, 1.09-1.20), respectively.

Dr. Liang and coauthors disclosed no relevant relationships with respect to the work presented at the CHEST meeting.

SOURCE: Liang B et al. CHEST 2020, Abstract A589.

Among individuals admitted to hospitals with sepsis, statin users had a lower mortality, compared with nonstatin users, according to a recent analysis focused on a large and diverse cohort of patients in California.

Mortality hazard ratios at 30 and 90 days were lower by about 20% for statin users admitted for sepsis, compared with nonstatin users, according to results of the retrospective cohort study.

Hydrophilic and synthetic statins had more favorable mortality outcomes, compared with lipophilic and fungal-derived statins, respectively, added investigator Brannen Liang, MD, a third-year internal medicine resident at Kaiser Permanente Los Angeles Medical Center.

These findings suggest a potential benefit of statins in patients with sepsis, with certain types of statins having a greater protective effect than others, according to Dr. Liang, who presented the original research in a presentation at the annual meeting of the American College of Chest Physicians, held virtually this year.

“I think there’s potential for extending the use of statins to other indications, such as sepsis,” Dr. Liang said in an interview, though he also cautioned that the present study is hypothesis generating and more research is necessary.

Using a certain statin type over another (i.e., a hydrophilic, synthetic statin) might be a consideration for populations who are at greater risk for sepsis, such as the immunocompromised, patients with diabetes, or elderly and who also require a statin for an indication such as hyperlipidemia, he added.

While the link between statin use and sepsis mortality outcomes is not new, this study is unique in that it replicates results of earlier studies in a large and diverse real-world population, Dr. Liang said.

“Numerous studies seem to suggest that statins may play a role in attenuating the mortality of patients admitted to the hospital with sepsis, for whatever reason – whether this is due to their anti-inflammatory effects, their lipid-lowering effects, or if they truly have an antimicrobial effect, which has been studied in vitro and in animal studies,” he said in an interview.

It’s impossible to definitively conclude from retrospective studies such as this whether statins reduce sepsis-related mortality risk, but the present study at least makes the case for using certain types of statins when they are indicated in high-risk patients, said Steven Q. Simpson, MD, FCCP, professor of medicine in the division of pulmonary and critical care medicine at the University of Kansas, Kansas City.

“If you have patients at high risk for sepsis and they need a statin, you could give consideration to using a hydrophilic and synthetic statin, rather than either of the other choices,” said Dr. Simpson, CHEST president-elect and senior advisor to the Solving Sepsis initiative of the Biomedical Advanced Research and Development Authority of the Department of Health & Human Services.

The retrospective cohort study by Dr. Liang and colleagues included a total of 137,019 individuals admitted for sepsis within the Kaiser Permanente Southern California health system between 2008 and 2018. Of that group, 36,908 were taking a statin.

Overall, the mean age of patients admitted for sepsis was 66.9 years, and 50.4% were female. Nearly 50% were White, about 12% were Black, 28% were Hispanic, and 8% were Asian. A diagnosis of ischemic heart disease was reported for 43% of statin users and 23% of nonusers, while diabetes mellitus was reported for 60% of statin users and 37% of nonusers (P < .0001 for both comparisons).

Differences in mortality favored statin users, compared with nonusers, with hazard ratios of 0.79 (95% confidence interval, 0.77-0.82) at 30 days and similarly, 0.79 (95% CI, 0.77-0.81) at 90 days, Dr. Liang reported, noting that the models were adjusted for age, race, sex, and comorbidities.

Further analysis suggested a mortality advantage of lipophilic, compared with hydrophilic statins, and an advantage of fungal-derived statins over synthetic-derived statins, the investigator added.

In the comparison of lipophilic statin users and hydrophilic statin users, the 30- and 90-day mortality HRs were 1.13 (95% CI, 1.02-1.26) and 1.17 (95% CI, 1.07-1.28), respectively, the data show. For fungal-derived statin users, compared with synthetic derived statin users, 30- and 90-day mortality HRs were 1.12 (95% CI, 1.06-1.19) and 1.14 (95% CI, 1.09-1.20), respectively.

Dr. Liang and coauthors disclosed no relevant relationships with respect to the work presented at the CHEST meeting.

SOURCE: Liang B et al. CHEST 2020, Abstract A589.

While the spring peak of COVID-19 was tough and traumatic for many residents and interns in a New York City health system, the experience may have accelerated their patient communication skills regarding difficult goals-of-care discussions, results of a recent survey suggest.

Breaking bad news was an everyday or every-other-day occurrence at the peak of the pandemic for nearly all of 50 of the trainees surveyed, who had worked at hospitals affiliated with the internal medicine residency program at the at the Icahn School of Medicine at Mount Sinai from March to June 2020.

However, trainees became significantly more comfortable and fluent in goals-of-care discussions during the pandemic, according to Patrick Tobin-Schnittger, MBBS, a third-year internal medicine resident in the Mount Sinai program.

“COVID-19 has obviously made a huge impact on the world, but I think it’s also made a huge impact on a whole generation of junior doctors,” said Dr. Tobin-Schnittger, who presented the findings in a late-breaking abstract session at the CHEST Annual Meeting, held virtually this year.

“It’ll be interesting to see what happens in the future as that generation matures, and I think one of the things is that we’re a lot more comfortable with end-of-life care,” he said in an interview conducted during the conference.

Nevertheless, coping with death may still be a challenge for many residents, according to Dr. Tobin-Schnittger. In the survey, internal medicine residents who had rarely encountered patient deaths suddenly found themselves experiencing deaths weekly, with more than one in five saying they were encountering it every day.

When asked to self-rate themselves according to Bugen’s Coping With Death scale, most participants had scores that suggested their ability to cope was suboptimal, the researcher said.

To help trainees cope with local COVID-19 surges, internal medicine residency programs should be implementing “breaking bad news” workshops and educating house staff on resilience in times of crisis, especially if it can be done virtually, according to Dr. Tobin-Schnittger.

“That could be done pretty quickly, and it could be done remotely so people could practice this from home,” he explained. “They wouldn’t even need to congregate in a big room.”

As a “mini-surge” of COVID-19 cases hits the United States, teaching self-care and coping techniques may also be important, said Mangala Narasimhan, DO, FCCP, director of critical care services at Northwell Health in New York City.

SOURCE: Tobin-Schnittger P. CHEST 2020. Late-breaking abstract. doi: 10.1016/j.chest.2020.09.040.

While the spring peak of COVID-19 was tough and traumatic for many residents and interns in a New York City health system, the experience may have accelerated their patient communication skills regarding difficult goals-of-care discussions, results of a recent survey suggest.

Breaking bad news was an everyday or every-other-day occurrence at the peak of the pandemic for nearly all of 50 of the trainees surveyed, who had worked at hospitals affiliated with the internal medicine residency program at the at the Icahn School of Medicine at Mount Sinai from March to June 2020.

However, trainees became significantly more comfortable and fluent in goals-of-care discussions during the pandemic, according to Patrick Tobin-Schnittger, MBBS, a third-year internal medicine resident in the Mount Sinai program.

“COVID-19 has obviously made a huge impact on the world, but I think it’s also made a huge impact on a whole generation of junior doctors,” said Dr. Tobin-Schnittger, who presented the findings in a late-breaking abstract session at the CHEST Annual Meeting, held virtually this year.

“It’ll be interesting to see what happens in the future as that generation matures, and I think one of the things is that we’re a lot more comfortable with end-of-life care,” he said in an interview conducted during the conference.

Nevertheless, coping with death may still be a challenge for many residents, according to Dr. Tobin-Schnittger. In the survey, internal medicine residents who had rarely encountered patient deaths suddenly found themselves experiencing deaths weekly, with more than one in five saying they were encountering it every day.

When asked to self-rate themselves according to Bugen’s Coping With Death scale, most participants had scores that suggested their ability to cope was suboptimal, the researcher said.

To help trainees cope with local COVID-19 surges, internal medicine residency programs should be implementing “breaking bad news” workshops and educating house staff on resilience in times of crisis, especially if it can be done virtually, according to Dr. Tobin-Schnittger.

“That could be done pretty quickly, and it could be done remotely so people could practice this from home,” he explained. “They wouldn’t even need to congregate in a big room.”

As a “mini-surge” of COVID-19 cases hits the United States, teaching self-care and coping techniques may also be important, said Mangala Narasimhan, DO, FCCP, director of critical care services at Northwell Health in New York City.

SOURCE: Tobin-Schnittger P. CHEST 2020. Late-breaking abstract. doi: 10.1016/j.chest.2020.09.040.

While the spring peak of COVID-19 was tough and traumatic for many residents and interns in a New York City health system, the experience may have accelerated their patient communication skills regarding difficult goals-of-care discussions, results of a recent survey suggest.

Breaking bad news was an everyday or every-other-day occurrence at the peak of the pandemic for nearly all of 50 of the trainees surveyed, who had worked at hospitals affiliated with the internal medicine residency program at the at the Icahn School of Medicine at Mount Sinai from March to June 2020.

However, trainees became significantly more comfortable and fluent in goals-of-care discussions during the pandemic, according to Patrick Tobin-Schnittger, MBBS, a third-year internal medicine resident in the Mount Sinai program.

“COVID-19 has obviously made a huge impact on the world, but I think it’s also made a huge impact on a whole generation of junior doctors,” said Dr. Tobin-Schnittger, who presented the findings in a late-breaking abstract session at the CHEST Annual Meeting, held virtually this year.

“It’ll be interesting to see what happens in the future as that generation matures, and I think one of the things is that we’re a lot more comfortable with end-of-life care,” he said in an interview conducted during the conference.

Nevertheless, coping with death may still be a challenge for many residents, according to Dr. Tobin-Schnittger. In the survey, internal medicine residents who had rarely encountered patient deaths suddenly found themselves experiencing deaths weekly, with more than one in five saying they were encountering it every day.

When asked to self-rate themselves according to Bugen’s Coping With Death scale, most participants had scores that suggested their ability to cope was suboptimal, the researcher said.

To help trainees cope with local COVID-19 surges, internal medicine residency programs should be implementing “breaking bad news” workshops and educating house staff on resilience in times of crisis, especially if it can be done virtually, according to Dr. Tobin-Schnittger.

“That could be done pretty quickly, and it could be done remotely so people could practice this from home,” he explained. “They wouldn’t even need to congregate in a big room.”

As a “mini-surge” of COVID-19 cases hits the United States, teaching self-care and coping techniques may also be important, said Mangala Narasimhan, DO, FCCP, director of critical care services at Northwell Health in New York City.

SOURCE: Tobin-Schnittger P. CHEST 2020. Late-breaking abstract. doi: 10.1016/j.chest.2020.09.040.

National guidelines failed to classify many younger African American lung cancer patients as being eligible for lung cancer screening in a recent retrospective study, the lead author reported at the annual meeting of the American College of Chest Physicians.

The finding highlights a health disparity issue that may be addressed through an update of those guidelines that is in the works, said Carol Velez Martinez, MD, a third-year internal medicine resident at Louisiana State University Health Sciences Center in Shreveport, La.

About one-third of the lung cancer patients in the retrospective cohort study were diagnosed before the age of 55 years, which means they would not have been recommended for screening with low-dose computed tomography (LDCT) based on the 2013 lung cancer guidelines from the United States Preventive Services Task Force (USPSTF), said Dr. Velez Martinez.

By contrast, 12.5% of screening-ineligible patients would have been counted as LDCT eligible based on guidelines from the National Comprehensive Cancer Network (NCCN), Dr. Velez Martinez and coauthors found in their analysis.

In a draft recommendation statement posted July 7, the USPSTF said they would now recommend that screening at age 50 years, rather than 55, and that the pack-years of smoking history that would make an individual eligible for screening would be dropped from 30 pack-years to 20, changes that task force members said would be more inclusive of African Americans and women.

Dr. Velez Martinez said she is looking forward to a formal recommendation from USPSTF soon: “I’m hoping that’s where they’re heading,” she said in an interview. “When I’m in practice as a resident, I actually bring it up to my patients, and if I have to call the insurance I don’t have a problem – but I still have to call them because they’re still going by the prior guidelines.”

“I think there are going to be a lot of other health disparities,” Dr. Revelo said in an interview. “[Dr. Velez Martinez’s] study was limited by the fact that she cared mostly for Caucasians and also African Americans, but maybe no Latinos or Hispanics that I’m sure would also be affected if we were looking to that in a bigger or national study.”

The 2013 USPSTF guidelines were based on benefits observed in the National Lung Screening Trial (NLST), which indicated a 20% relative risk reduction in death from lung cancer; however, the generalizability of the study beyond White males has been questioned, said Dr. Velez Martinez in a presentation at the CHEST annual meeting.

About 90% of NSLT participants were White and 59% were male, according to results published in 2011.

Other studies have shown that African Americans are more likely to get lung cancer than Whites, despite comparable smoking rates between the races, and that African American men are more likely to die from lung cancer than White men, Dr. Velez Martinez said. Many African Americans live below the poverty line, which means they have limited resources for insurance and health providers, and they also participate less often in clinical trials, she added.

In their retrospective observational cohort study, Dr. Velez Martinez and coinvestigators reviewed 1,500 medical records of patients with newly diagnosed stage 1-4 lung cancers from the LSU Health Science Center Shreveport between 2011 and 2015.

They found that 33% of those lung cancer patients were diagnosed before the age of 55 years, meaning they did not meet the 2013 USPSTF screening guidelines, which recommend annual LDCT in adults aged 55-80 years with a 30 pack-year smoking history who currently smoke or have quit within the past 15 years.

Next, they sought to classify those screening-ineligible patients based on NCCN guidelines, which recommend LDCT in patients 50 years of age or older with at least a 20 pack-year smoking history and a 6-year risk of lung cancer of at least 1.3% based on the Tammemagi lung cancer risk calculator. The Tammemagi calculator considers factors such as age, education, body mass index, prior lung disease, familial cancer history, race and ethnicity, and smoking history.

After applying the risk stratification, the investigators found that 12.5% of these patients would have been categorized as high risk and therefore recommended for LDCT, and of that group, more than 65% were African American, Dr. Velez Martinez reported.

Dr. Revelo, who chaired the CHEST session where the findings were reported, said that shared decision-making will still be as important regardless of any changes to lung screening guidelines given the recognized potential harms of LDCT screening, such as false positives, radiation exposure, and psychological distress.

“I think we will continue to have a very personal conversation and make important decisions focused on what the patient wants,” he said.

Authors reported no disclosures.

National guidelines failed to classify many younger African American lung cancer patients as being eligible for lung cancer screening in a recent retrospective study, the lead author reported at the annual meeting of the American College of Chest Physicians.

The finding highlights a health disparity issue that may be addressed through an update of those guidelines that is in the works, said Carol Velez Martinez, MD, a third-year internal medicine resident at Louisiana State University Health Sciences Center in Shreveport, La.

About one-third of the lung cancer patients in the retrospective cohort study were diagnosed before the age of 55 years, which means they would not have been recommended for screening with low-dose computed tomography (LDCT) based on the 2013 lung cancer guidelines from the United States Preventive Services Task Force (USPSTF), said Dr. Velez Martinez.

By contrast, 12.5% of screening-ineligible patients would have been counted as LDCT eligible based on guidelines from the National Comprehensive Cancer Network (NCCN), Dr. Velez Martinez and coauthors found in their analysis.

In a draft recommendation statement posted July 7, the USPSTF said they would now recommend that screening at age 50 years, rather than 55, and that the pack-years of smoking history that would make an individual eligible for screening would be dropped from 30 pack-years to 20, changes that task force members said would be more inclusive of African Americans and women.

Dr. Velez Martinez said she is looking forward to a formal recommendation from USPSTF soon: “I’m hoping that’s where they’re heading,” she said in an interview. “When I’m in practice as a resident, I actually bring it up to my patients, and if I have to call the insurance I don’t have a problem – but I still have to call them because they’re still going by the prior guidelines.”

“I think there are going to be a lot of other health disparities,” Dr. Revelo said in an interview. “[Dr. Velez Martinez’s] study was limited by the fact that she cared mostly for Caucasians and also African Americans, but maybe no Latinos or Hispanics that I’m sure would also be affected if we were looking to that in a bigger or national study.”

The 2013 USPSTF guidelines were based on benefits observed in the National Lung Screening Trial (NLST), which indicated a 20% relative risk reduction in death from lung cancer; however, the generalizability of the study beyond White males has been questioned, said Dr. Velez Martinez in a presentation at the CHEST annual meeting.

About 90% of NSLT participants were White and 59% were male, according to results published in 2011.

Other studies have shown that African Americans are more likely to get lung cancer than Whites, despite comparable smoking rates between the races, and that African American men are more likely to die from lung cancer than White men, Dr. Velez Martinez said. Many African Americans live below the poverty line, which means they have limited resources for insurance and health providers, and they also participate less often in clinical trials, she added.

In their retrospective observational cohort study, Dr. Velez Martinez and coinvestigators reviewed 1,500 medical records of patients with newly diagnosed stage 1-4 lung cancers from the LSU Health Science Center Shreveport between 2011 and 2015.

They found that 33% of those lung cancer patients were diagnosed before the age of 55 years, meaning they did not meet the 2013 USPSTF screening guidelines, which recommend annual LDCT in adults aged 55-80 years with a 30 pack-year smoking history who currently smoke or have quit within the past 15 years.

Next, they sought to classify those screening-ineligible patients based on NCCN guidelines, which recommend LDCT in patients 50 years of age or older with at least a 20 pack-year smoking history and a 6-year risk of lung cancer of at least 1.3% based on the Tammemagi lung cancer risk calculator. The Tammemagi calculator considers factors such as age, education, body mass index, prior lung disease, familial cancer history, race and ethnicity, and smoking history.

After applying the risk stratification, the investigators found that 12.5% of these patients would have been categorized as high risk and therefore recommended for LDCT, and of that group, more than 65% were African American, Dr. Velez Martinez reported.

Dr. Revelo, who chaired the CHEST session where the findings were reported, said that shared decision-making will still be as important regardless of any changes to lung screening guidelines given the recognized potential harms of LDCT screening, such as false positives, radiation exposure, and psychological distress.

“I think we will continue to have a very personal conversation and make important decisions focused on what the patient wants,” he said.

Authors reported no disclosures.

National guidelines failed to classify many younger African American lung cancer patients as being eligible for lung cancer screening in a recent retrospective study, the lead author reported at the annual meeting of the American College of Chest Physicians.

The finding highlights a health disparity issue that may be addressed through an update of those guidelines that is in the works, said Carol Velez Martinez, MD, a third-year internal medicine resident at Louisiana State University Health Sciences Center in Shreveport, La.

About one-third of the lung cancer patients in the retrospective cohort study were diagnosed before the age of 55 years, which means they would not have been recommended for screening with low-dose computed tomography (LDCT) based on the 2013 lung cancer guidelines from the United States Preventive Services Task Force (USPSTF), said Dr. Velez Martinez.

By contrast, 12.5% of screening-ineligible patients would have been counted as LDCT eligible based on guidelines from the National Comprehensive Cancer Network (NCCN), Dr. Velez Martinez and coauthors found in their analysis.

In a draft recommendation statement posted July 7, the USPSTF said they would now recommend that screening at age 50 years, rather than 55, and that the pack-years of smoking history that would make an individual eligible for screening would be dropped from 30 pack-years to 20, changes that task force members said would be more inclusive of African Americans and women.

Dr. Velez Martinez said she is looking forward to a formal recommendation from USPSTF soon: “I’m hoping that’s where they’re heading,” she said in an interview. “When I’m in practice as a resident, I actually bring it up to my patients, and if I have to call the insurance I don’t have a problem – but I still have to call them because they’re still going by the prior guidelines.”

“I think there are going to be a lot of other health disparities,” Dr. Revelo said in an interview. “[Dr. Velez Martinez’s] study was limited by the fact that she cared mostly for Caucasians and also African Americans, but maybe no Latinos or Hispanics that I’m sure would also be affected if we were looking to that in a bigger or national study.”

The 2013 USPSTF guidelines were based on benefits observed in the National Lung Screening Trial (NLST), which indicated a 20% relative risk reduction in death from lung cancer; however, the generalizability of the study beyond White males has been questioned, said Dr. Velez Martinez in a presentation at the CHEST annual meeting.

About 90% of NSLT participants were White and 59% were male, according to results published in 2011.

Other studies have shown that African Americans are more likely to get lung cancer than Whites, despite comparable smoking rates between the races, and that African American men are more likely to die from lung cancer than White men, Dr. Velez Martinez said. Many African Americans live below the poverty line, which means they have limited resources for insurance and health providers, and they also participate less often in clinical trials, she added.

In their retrospective observational cohort study, Dr. Velez Martinez and coinvestigators reviewed 1,500 medical records of patients with newly diagnosed stage 1-4 lung cancers from the LSU Health Science Center Shreveport between 2011 and 2015.

They found that 33% of those lung cancer patients were diagnosed before the age of 55 years, meaning they did not meet the 2013 USPSTF screening guidelines, which recommend annual LDCT in adults aged 55-80 years with a 30 pack-year smoking history who currently smoke or have quit within the past 15 years.

Next, they sought to classify those screening-ineligible patients based on NCCN guidelines, which recommend LDCT in patients 50 years of age or older with at least a 20 pack-year smoking history and a 6-year risk of lung cancer of at least 1.3% based on the Tammemagi lung cancer risk calculator. The Tammemagi calculator considers factors such as age, education, body mass index, prior lung disease, familial cancer history, race and ethnicity, and smoking history.

After applying the risk stratification, the investigators found that 12.5% of these patients would have been categorized as high risk and therefore recommended for LDCT, and of that group, more than 65% were African American, Dr. Velez Martinez reported.

Dr. Revelo, who chaired the CHEST session where the findings were reported, said that shared decision-making will still be as important regardless of any changes to lung screening guidelines given the recognized potential harms of LDCT screening, such as false positives, radiation exposure, and psychological distress.

“I think we will continue to have a very personal conversation and make important decisions focused on what the patient wants,” he said.

Authors reported no disclosures.