Hodgkin Lymphoma

Photo by Rhoda Baer

A new study suggests cancer patients may be open to using marijuana, but healthcare providers may be falling short in educating patients on marijuana use.

This single-center study included more than 900 cancer patients in a US state with legalized medicinal and recreational marijuana.

More than 90% of the patients surveyed said they were interested in learning more about marijuana use in the context of cancer, and nearly three-quarters of the patients wanted their cancer care providers to supply information on the topic.

However, less than 15% of patients received such information from providers. Instead, patients learned about marijuana use from sources such as the Internet or other patients.

“Cancer patients desire but are not receiving information from their cancer doctors about marijuana use during their treatment, so many of them are seeking information from alternate, non-scientific sources,” said Steven Pergam, MD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington.

Dr Pergam and his colleagues reported this finding in the journal Cancer.

Eight US states and the District of Columbia have legalized recreational marijuana, and more than half of states have passed laws allowing for medical marijuana in some form. Marijuana is purported to alleviate symptoms related to cancer treatment, but patterns of use among cancer patients are not well known.

To investigate, Dr Pergam and his colleagues surveyed 926 patients at the Seattle Cancer Center Alliance. The patients’ median age was 58, 52% were male, and 59% had at least a college degree. Thirty-four percent of patients had hematologic malignancies.

Results

Sixty-six percent of patients said they had used marijuana in the past, 24% used in the last year, and 21% used in the last month.

A random analysis of patient urine samples showed that 14% of patients had evidence of recent marijuana use, similar to the 18% of users who reported at least weekly marijuana use.

When compared to patients who never used marijuana and those who previously used marijuana but quit, patients currently using marijuana said they were more likely to do so because the drug had been legalized. Women were more likely than men to use because of legalization.

Current marijuana users were younger, had less education, and were less likely to have undergone hematopoietic stem cell transplant. There was no difference in marijuana use according to a patient’s cancer type.

Most patients said they used marijuana to relieve physical symptoms (75%) and neuropsychiatric symptoms (63%), though some also used it recreationally (35%).

In addition, 26% of current marijuana users said they believed the drug was helping to treat their cancer. And 5% of these users said this was their only reason for marijuana use.

Most patients (92%) said they wanted to learn more about marijuana and cancer. However, the level of interest varied with age, with younger patients expressing the most interest.

Seventy-four percent of patients said they would prefer to get information on marijuana use from their cancer team, but less than 15% received such information from their cancer physician or nurse.

Patients said they received information on marijuana and cancer from friends and family, newspaper and magazine articles, websites and blogs, or another cancer patient.

More than a third of patients said they had not received any information on marijuana and cancer.

“We hope that this study helps to open up the door for more studies aimed at evaluating the risks and benefits of marijuana in this population,” Dr Pergam said. “This is important because if we do not educate our patients about marijuana, they will continue to get their information elsewhere.”

Photo by Rhoda Baer

A new study suggests cancer patients may be open to using marijuana, but healthcare providers may be falling short in educating patients on marijuana use.

This single-center study included more than 900 cancer patients in a US state with legalized medicinal and recreational marijuana.

More than 90% of the patients surveyed said they were interested in learning more about marijuana use in the context of cancer, and nearly three-quarters of the patients wanted their cancer care providers to supply information on the topic.

However, less than 15% of patients received such information from providers. Instead, patients learned about marijuana use from sources such as the Internet or other patients.

“Cancer patients desire but are not receiving information from their cancer doctors about marijuana use during their treatment, so many of them are seeking information from alternate, non-scientific sources,” said Steven Pergam, MD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington.

Dr Pergam and his colleagues reported this finding in the journal Cancer.

Eight US states and the District of Columbia have legalized recreational marijuana, and more than half of states have passed laws allowing for medical marijuana in some form. Marijuana is purported to alleviate symptoms related to cancer treatment, but patterns of use among cancer patients are not well known.

To investigate, Dr Pergam and his colleagues surveyed 926 patients at the Seattle Cancer Center Alliance. The patients’ median age was 58, 52% were male, and 59% had at least a college degree. Thirty-four percent of patients had hematologic malignancies.

Results

Sixty-six percent of patients said they had used marijuana in the past, 24% used in the last year, and 21% used in the last month.

A random analysis of patient urine samples showed that 14% of patients had evidence of recent marijuana use, similar to the 18% of users who reported at least weekly marijuana use.

When compared to patients who never used marijuana and those who previously used marijuana but quit, patients currently using marijuana said they were more likely to do so because the drug had been legalized. Women were more likely than men to use because of legalization.

Current marijuana users were younger, had less education, and were less likely to have undergone hematopoietic stem cell transplant. There was no difference in marijuana use according to a patient’s cancer type.

Most patients said they used marijuana to relieve physical symptoms (75%) and neuropsychiatric symptoms (63%), though some also used it recreationally (35%).

In addition, 26% of current marijuana users said they believed the drug was helping to treat their cancer. And 5% of these users said this was their only reason for marijuana use.

Most patients (92%) said they wanted to learn more about marijuana and cancer. However, the level of interest varied with age, with younger patients expressing the most interest.

Seventy-four percent of patients said they would prefer to get information on marijuana use from their cancer team, but less than 15% received such information from their cancer physician or nurse.

Patients said they received information on marijuana and cancer from friends and family, newspaper and magazine articles, websites and blogs, or another cancer patient.

More than a third of patients said they had not received any information on marijuana and cancer.

“We hope that this study helps to open up the door for more studies aimed at evaluating the risks and benefits of marijuana in this population,” Dr Pergam said. “This is important because if we do not educate our patients about marijuana, they will continue to get their information elsewhere.”

Photo by Rhoda Baer

A new study suggests cancer patients may be open to using marijuana, but healthcare providers may be falling short in educating patients on marijuana use.

This single-center study included more than 900 cancer patients in a US state with legalized medicinal and recreational marijuana.

More than 90% of the patients surveyed said they were interested in learning more about marijuana use in the context of cancer, and nearly three-quarters of the patients wanted their cancer care providers to supply information on the topic.

However, less than 15% of patients received such information from providers. Instead, patients learned about marijuana use from sources such as the Internet or other patients.

“Cancer patients desire but are not receiving information from their cancer doctors about marijuana use during their treatment, so many of them are seeking information from alternate, non-scientific sources,” said Steven Pergam, MD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington.

Dr Pergam and his colleagues reported this finding in the journal Cancer.

Eight US states and the District of Columbia have legalized recreational marijuana, and more than half of states have passed laws allowing for medical marijuana in some form. Marijuana is purported to alleviate symptoms related to cancer treatment, but patterns of use among cancer patients are not well known.

To investigate, Dr Pergam and his colleagues surveyed 926 patients at the Seattle Cancer Center Alliance. The patients’ median age was 58, 52% were male, and 59% had at least a college degree. Thirty-four percent of patients had hematologic malignancies.

Results

Sixty-six percent of patients said they had used marijuana in the past, 24% used in the last year, and 21% used in the last month.

A random analysis of patient urine samples showed that 14% of patients had evidence of recent marijuana use, similar to the 18% of users who reported at least weekly marijuana use.

When compared to patients who never used marijuana and those who previously used marijuana but quit, patients currently using marijuana said they were more likely to do so because the drug had been legalized. Women were more likely than men to use because of legalization.

Current marijuana users were younger, had less education, and were less likely to have undergone hematopoietic stem cell transplant. There was no difference in marijuana use according to a patient’s cancer type.

Most patients said they used marijuana to relieve physical symptoms (75%) and neuropsychiatric symptoms (63%), though some also used it recreationally (35%).

In addition, 26% of current marijuana users said they believed the drug was helping to treat their cancer. And 5% of these users said this was their only reason for marijuana use.

Most patients (92%) said they wanted to learn more about marijuana and cancer. However, the level of interest varied with age, with younger patients expressing the most interest.

Seventy-four percent of patients said they would prefer to get information on marijuana use from their cancer team, but less than 15% received such information from their cancer physician or nurse.

Patients said they received information on marijuana and cancer from friends and family, newspaper and magazine articles, websites and blogs, or another cancer patient.

More than a third of patients said they had not received any information on marijuana and cancer.

“We hope that this study helps to open up the door for more studies aimed at evaluating the risks and benefits of marijuana in this population,” Dr Pergam said. “This is important because if we do not educate our patients about marijuana, they will continue to get their information elsewhere.”

Hodgkin lymphoma patients who received haploidentical (HAPLO) allogeneic hematopoietic cell transplantation after a nonmyeloablative regimen and posttransplantation cyclophosphamide had outcomes similar to those of patients who had conventional transplants, in a retrospective analysis of 709 adult patients in the European Society for Blood and Marrow Transplantation database.

In addition, patients who underwent HAPLO had a lower incidence of extensive chronic graft-versus host disease (cGVHD) compared with HLA-matched unrelated donor (MUD) transplantation and higher cGVHD-free/relapse-free survival compared with HLA-matched sibling donor (SIB) transplantation.

“Use of HAPLO donors may allow patients to proceed more rapidly to transplantation, avoiding the time needed to complete a formal MUD search and arrange for graft collection at a remote center,” wrote Carmen Martinez, MD, of the Institute of Hematology and Oncology, Hospital Clinic, Barcelona. The study was published online in the Journal of Clinical Oncology. Conventional donors are unavailable for a significant proportion of Hodgkin lymphoma patients.

Recommendations from the European Society for Blood and Marrow Transplantation consider alloHCT to be the standard treatment option for eligible patients with Hodgkin lymphoma who have relapsed after undergoing autologous hematopoietic cell transplantation and SIB or MUD. For the retrospective study, outcomes were compared for 338 patients who had SIB transplants, 273 patients who had MUD transplants, and 98 patients who received HAPLO transplants after a nonmyeloablative regimen and posttransplantation cyclophosphamide (PTCy) as GVHD prophylaxis.

The rate of grade II-IV acute GVHD after HAPLO was higher than after SIB (33% vs. 18%; P = .003), and was comparable to the rate with MUD (30%). The rates of grade III-IV acute GVHD were similar for all three cohorts (HAPLO, 9%; SIB, 6%; and MUD, 9%).

At 1 year, the cumulative rate of chronic GVHD was 26% after HAPLO and 25% after SIB; it was significantly higher at 41% after MUD (P = .017).

The cumulative incidence of nonrelapse mortality at 1 year was 17% with HAPLO, 13% with SIB, and significantly higher at 21% with MUD (P = .003). At 2 years, the cumulative incidence of relapse or progression was 39%, 49%, and 32%, respectively. The difference was significantly higher for SIB than HAPLO (P = .047) and MUD (P = .001).

There were no significant differences in 2-year overall survival, but MUD transplant recipients had lower overall survival (62%; 95% CI, 56 to 68; P = .039) compared with SIB transplant recipients.

“Whether HAPLO transplantation is the first choice instead of MUD transplantation and whether it can eventually substitute SIB transplantation in specific subgroups of patients must be assessed within the context of a randomized prospective clinical trial,” wrote Dr. Martinez and colleagues.

Hodgkin lymphoma patients who received haploidentical (HAPLO) allogeneic hematopoietic cell transplantation after a nonmyeloablative regimen and posttransplantation cyclophosphamide had outcomes similar to those of patients who had conventional transplants, in a retrospective analysis of 709 adult patients in the European Society for Blood and Marrow Transplantation database.

In addition, patients who underwent HAPLO had a lower incidence of extensive chronic graft-versus host disease (cGVHD) compared with HLA-matched unrelated donor (MUD) transplantation and higher cGVHD-free/relapse-free survival compared with HLA-matched sibling donor (SIB) transplantation.

“Use of HAPLO donors may allow patients to proceed more rapidly to transplantation, avoiding the time needed to complete a formal MUD search and arrange for graft collection at a remote center,” wrote Carmen Martinez, MD, of the Institute of Hematology and Oncology, Hospital Clinic, Barcelona. The study was published online in the Journal of Clinical Oncology. Conventional donors are unavailable for a significant proportion of Hodgkin lymphoma patients.

Recommendations from the European Society for Blood and Marrow Transplantation consider alloHCT to be the standard treatment option for eligible patients with Hodgkin lymphoma who have relapsed after undergoing autologous hematopoietic cell transplantation and SIB or MUD. For the retrospective study, outcomes were compared for 338 patients who had SIB transplants, 273 patients who had MUD transplants, and 98 patients who received HAPLO transplants after a nonmyeloablative regimen and posttransplantation cyclophosphamide (PTCy) as GVHD prophylaxis.

The rate of grade II-IV acute GVHD after HAPLO was higher than after SIB (33% vs. 18%; P = .003), and was comparable to the rate with MUD (30%). The rates of grade III-IV acute GVHD were similar for all three cohorts (HAPLO, 9%; SIB, 6%; and MUD, 9%).

At 1 year, the cumulative rate of chronic GVHD was 26% after HAPLO and 25% after SIB; it was significantly higher at 41% after MUD (P = .017).

The cumulative incidence of nonrelapse mortality at 1 year was 17% with HAPLO, 13% with SIB, and significantly higher at 21% with MUD (P = .003). At 2 years, the cumulative incidence of relapse or progression was 39%, 49%, and 32%, respectively. The difference was significantly higher for SIB than HAPLO (P = .047) and MUD (P = .001).

There were no significant differences in 2-year overall survival, but MUD transplant recipients had lower overall survival (62%; 95% CI, 56 to 68; P = .039) compared with SIB transplant recipients.

“Whether HAPLO transplantation is the first choice instead of MUD transplantation and whether it can eventually substitute SIB transplantation in specific subgroups of patients must be assessed within the context of a randomized prospective clinical trial,” wrote Dr. Martinez and colleagues.

Hodgkin lymphoma patients who received haploidentical (HAPLO) allogeneic hematopoietic cell transplantation after a nonmyeloablative regimen and posttransplantation cyclophosphamide had outcomes similar to those of patients who had conventional transplants, in a retrospective analysis of 709 adult patients in the European Society for Blood and Marrow Transplantation database.

In addition, patients who underwent HAPLO had a lower incidence of extensive chronic graft-versus host disease (cGVHD) compared with HLA-matched unrelated donor (MUD) transplantation and higher cGVHD-free/relapse-free survival compared with HLA-matched sibling donor (SIB) transplantation.

“Use of HAPLO donors may allow patients to proceed more rapidly to transplantation, avoiding the time needed to complete a formal MUD search and arrange for graft collection at a remote center,” wrote Carmen Martinez, MD, of the Institute of Hematology and Oncology, Hospital Clinic, Barcelona. The study was published online in the Journal of Clinical Oncology. Conventional donors are unavailable for a significant proportion of Hodgkin lymphoma patients.

Recommendations from the European Society for Blood and Marrow Transplantation consider alloHCT to be the standard treatment option for eligible patients with Hodgkin lymphoma who have relapsed after undergoing autologous hematopoietic cell transplantation and SIB or MUD. For the retrospective study, outcomes were compared for 338 patients who had SIB transplants, 273 patients who had MUD transplants, and 98 patients who received HAPLO transplants after a nonmyeloablative regimen and posttransplantation cyclophosphamide (PTCy) as GVHD prophylaxis.

The rate of grade II-IV acute GVHD after HAPLO was higher than after SIB (33% vs. 18%; P = .003), and was comparable to the rate with MUD (30%). The rates of grade III-IV acute GVHD were similar for all three cohorts (HAPLO, 9%; SIB, 6%; and MUD, 9%).

At 1 year, the cumulative rate of chronic GVHD was 26% after HAPLO and 25% after SIB; it was significantly higher at 41% after MUD (P = .017).

The cumulative incidence of nonrelapse mortality at 1 year was 17% with HAPLO, 13% with SIB, and significantly higher at 21% with MUD (P = .003). At 2 years, the cumulative incidence of relapse or progression was 39%, 49%, and 32%, respectively. The difference was significantly higher for SIB than HAPLO (P = .047) and MUD (P = .001).

There were no significant differences in 2-year overall survival, but MUD transplant recipients had lower overall survival (62%; 95% CI, 56 to 68; P = .039) compared with SIB transplant recipients.

“Whether HAPLO transplantation is the first choice instead of MUD transplantation and whether it can eventually substitute SIB transplantation in specific subgroups of patients must be assessed within the context of a randomized prospective clinical trial,” wrote Dr. Martinez and colleagues.

Photo by Rhoda Baer

Deaths from cancer are on the decline in the US, but new cases of cancer are on the rise, according to the 7th annual American Association for Cancer Research (AACR) Cancer Progress Report.

The data suggest the cancer death rate declined by 35% from 1991 to 2014 for children and by 25% for adults, a reduction that translates to 2.1 million cancer deaths avoided.

However, 600,920 people in the US are projected to die from cancer in 2017.

And the number of new cancer cases is predicted to rise from 1.7 million in 2017 to 2.3 million in 2030.

The report also estimates there will be 62,130 new cases of leukemia in 2017 and 24,500 leukemia deaths this year.

This includes:

• 5970 cases of acute lymphocytic leukemia and 1440 deaths
• 20,110 cases of chronic lymphocytic leukemia and 4660 deaths
• 21,380 cases of acute myeloid leukemia (AML) and 10,590 deaths
• 8950 cases of chronic myeloid leukemia and 1080 deaths.

The estimate for lymphomas is 80,500 new cases and 21,210 deaths.

This includes:

• 8260 cases of Hodgkin lymphoma (HL) and 1070 deaths
• 72,240 cases of non-Hodgkin lymphoma and 20,140 deaths.

The estimate for myeloma is 30,280 new cases and 12,590 deaths.

The report says the estimated new cases of cancer are based on cancer incidence rates from 49 states and the District of Columbia from 1995 through 2013, as reported by the North American Association of Central Cancer Registries. This represents about 98% of the US population.

The estimated deaths are based on US mortality data from 1997 through 2013, taken from the National Center for Health Statistics of the Centers for Disease Control and Prevention.

Drug approvals

The AACR report notes that, between August 1, 2016, and July 31, 2017, the US Food and Drug Administration (FDA) approved new uses for 15 anticancer agents, 9 of which had no previous FDA approval.

Five of the agents are immunotherapies, which the report dubs “revolutionary treatments that are increasing survival and improving quality of life for patients.”

Among the recently approved therapies are 3 used for hematology indications:

• Ibrutinib (Imbruvica), approved to treat patients with relapsed/refractory marginal zone lymphoma who require systemic therapy and have received at least 1 prior anti-CD20-based therapy
• Midostaurin (Rydapt), approved as monotherapy for adults with advanced systemic mastocytosis and for use in combination with standard cytarabine and daunorubicin induction, followed by cytarabine consolidation, in adults with newly diagnosed AML who are FLT3 mutation-positive, as detected by an FDA-approved test.
• Pembrolizumab (Keytruda), approved to treat adult and pediatric patients with refractory classical HL or those with classical HL who have relapsed after 3 or more prior lines of therapy.

Disparities and costs

The AACR report points out that advances against cancer have not benefited everyone equally, and cancer health disparities are some of the most pressing challenges.

Among the disparities listed is the fact that adolescents and young adults (ages 15 to 39) with AML have a 5-year relative survival rate that is 22% lower than that of children (ages 1 to 14) with AML.

And Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.

Another concern mentioned in the report is the cost of cancer care. The direct medical costs of cancer care in 2014 were estimated to be nearly $87.6 billion. This number does not include the indirect costs of lost productivity due to cancer-related morbidity and mortality.

With this in mind, the AACR is calling for a $2 billion increase in funding for the National Institutes of Health in fiscal year 2018, for a total funding level of $36.2 billion.

The AACR also recommends an $80 million increase in the FDA budget, bringing it to $2.8 billion for fiscal year 2018.

Photo by Rhoda Baer

Deaths from cancer are on the decline in the US, but new cases of cancer are on the rise, according to the 7th annual American Association for Cancer Research (AACR) Cancer Progress Report.

The data suggest the cancer death rate declined by 35% from 1991 to 2014 for children and by 25% for adults, a reduction that translates to 2.1 million cancer deaths avoided.

However, 600,920 people in the US are projected to die from cancer in 2017.

And the number of new cancer cases is predicted to rise from 1.7 million in 2017 to 2.3 million in 2030.

The report also estimates there will be 62,130 new cases of leukemia in 2017 and 24,500 leukemia deaths this year.

This includes:

• 5970 cases of acute lymphocytic leukemia and 1440 deaths
• 20,110 cases of chronic lymphocytic leukemia and 4660 deaths
• 21,380 cases of acute myeloid leukemia (AML) and 10,590 deaths
• 8950 cases of chronic myeloid leukemia and 1080 deaths.

The estimate for lymphomas is 80,500 new cases and 21,210 deaths.

This includes:

• 8260 cases of Hodgkin lymphoma (HL) and 1070 deaths
• 72,240 cases of non-Hodgkin lymphoma and 20,140 deaths.

The estimate for myeloma is 30,280 new cases and 12,590 deaths.

The report says the estimated new cases of cancer are based on cancer incidence rates from 49 states and the District of Columbia from 1995 through 2013, as reported by the North American Association of Central Cancer Registries. This represents about 98% of the US population.

The estimated deaths are based on US mortality data from 1997 through 2013, taken from the National Center for Health Statistics of the Centers for Disease Control and Prevention.

Drug approvals

The AACR report notes that, between August 1, 2016, and July 31, 2017, the US Food and Drug Administration (FDA) approved new uses for 15 anticancer agents, 9 of which had no previous FDA approval.

Five of the agents are immunotherapies, which the report dubs “revolutionary treatments that are increasing survival and improving quality of life for patients.”

Among the recently approved therapies are 3 used for hematology indications:

• Ibrutinib (Imbruvica), approved to treat patients with relapsed/refractory marginal zone lymphoma who require systemic therapy and have received at least 1 prior anti-CD20-based therapy
• Midostaurin (Rydapt), approved as monotherapy for adults with advanced systemic mastocytosis and for use in combination with standard cytarabine and daunorubicin induction, followed by cytarabine consolidation, in adults with newly diagnosed AML who are FLT3 mutation-positive, as detected by an FDA-approved test.
• Pembrolizumab (Keytruda), approved to treat adult and pediatric patients with refractory classical HL or those with classical HL who have relapsed after 3 or more prior lines of therapy.

Disparities and costs

The AACR report points out that advances against cancer have not benefited everyone equally, and cancer health disparities are some of the most pressing challenges.

Among the disparities listed is the fact that adolescents and young adults (ages 15 to 39) with AML have a 5-year relative survival rate that is 22% lower than that of children (ages 1 to 14) with AML.

And Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.

Another concern mentioned in the report is the cost of cancer care. The direct medical costs of cancer care in 2014 were estimated to be nearly $87.6 billion. This number does not include the indirect costs of lost productivity due to cancer-related morbidity and mortality.

With this in mind, the AACR is calling for a $2 billion increase in funding for the National Institutes of Health in fiscal year 2018, for a total funding level of $36.2 billion.

The AACR also recommends an $80 million increase in the FDA budget, bringing it to $2.8 billion for fiscal year 2018.

Photo by Rhoda Baer

Deaths from cancer are on the decline in the US, but new cases of cancer are on the rise, according to the 7th annual American Association for Cancer Research (AACR) Cancer Progress Report.

The data suggest the cancer death rate declined by 35% from 1991 to 2014 for children and by 25% for adults, a reduction that translates to 2.1 million cancer deaths avoided.

However, 600,920 people in the US are projected to die from cancer in 2017.

And the number of new cancer cases is predicted to rise from 1.7 million in 2017 to 2.3 million in 2030.

The report also estimates there will be 62,130 new cases of leukemia in 2017 and 24,500 leukemia deaths this year.

This includes:

• 5970 cases of acute lymphocytic leukemia and 1440 deaths
• 20,110 cases of chronic lymphocytic leukemia and 4660 deaths
• 21,380 cases of acute myeloid leukemia (AML) and 10,590 deaths
• 8950 cases of chronic myeloid leukemia and 1080 deaths.

The estimate for lymphomas is 80,500 new cases and 21,210 deaths.

This includes:

• 8260 cases of Hodgkin lymphoma (HL) and 1070 deaths
• 72,240 cases of non-Hodgkin lymphoma and 20,140 deaths.

The estimate for myeloma is 30,280 new cases and 12,590 deaths.

The report says the estimated new cases of cancer are based on cancer incidence rates from 49 states and the District of Columbia from 1995 through 2013, as reported by the North American Association of Central Cancer Registries. This represents about 98% of the US population.

The estimated deaths are based on US mortality data from 1997 through 2013, taken from the National Center for Health Statistics of the Centers for Disease Control and Prevention.

Drug approvals

The AACR report notes that, between August 1, 2016, and July 31, 2017, the US Food and Drug Administration (FDA) approved new uses for 15 anticancer agents, 9 of which had no previous FDA approval.

Five of the agents are immunotherapies, which the report dubs “revolutionary treatments that are increasing survival and improving quality of life for patients.”

Among the recently approved therapies are 3 used for hematology indications:

• Ibrutinib (Imbruvica), approved to treat patients with relapsed/refractory marginal zone lymphoma who require systemic therapy and have received at least 1 prior anti-CD20-based therapy
• Midostaurin (Rydapt), approved as monotherapy for adults with advanced systemic mastocytosis and for use in combination with standard cytarabine and daunorubicin induction, followed by cytarabine consolidation, in adults with newly diagnosed AML who are FLT3 mutation-positive, as detected by an FDA-approved test.
• Pembrolizumab (Keytruda), approved to treat adult and pediatric patients with refractory classical HL or those with classical HL who have relapsed after 3 or more prior lines of therapy.

Disparities and costs

The AACR report points out that advances against cancer have not benefited everyone equally, and cancer health disparities are some of the most pressing challenges.

Among the disparities listed is the fact that adolescents and young adults (ages 15 to 39) with AML have a 5-year relative survival rate that is 22% lower than that of children (ages 1 to 14) with AML.

And Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.

Another concern mentioned in the report is the cost of cancer care. The direct medical costs of cancer care in 2014 were estimated to be nearly $87.6 billion. This number does not include the indirect costs of lost productivity due to cancer-related morbidity and mortality.

With this in mind, the AACR is calling for a $2 billion increase in funding for the National Institutes of Health in fiscal year 2018, for a total funding level of $36.2 billion.

The AACR also recommends an $80 million increase in the FDA budget, bringing it to $2.8 billion for fiscal year 2018.

Photo courtesy of NIH

Adult survivors of childhood cancer have a greater cumulative burden of chronic health conditions than the general public, according to research published in The Lancet.

The study showed that, by age 50, childhood cancer survivors (CCSs) had experienced, on average, 17.1 chronic health conditions, and matched control subjects had experienced 9.2.

“The cumulative burden of chronic disease revealed in this analysis, along with the complexity and severity of chronic conditions some survivors experience, found childhood cancer survivors to be a vulnerable, medically complex population,” said study author Nickhill Bhakta, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

For this study, Dr Bhakta and his colleagues assessed the lifelong impact of 168 chronic health conditions—such as hepatic, thyroid, ocular, and reproductive disorders—on CCSs and control subjects.

The 3010 evaluable CCSs had survived 10 years or longer from their initial cancer diagnosis and were 18 years or older as of June 30, 2015. The 272 controls had no history of pediatric cancer and were matched to CCSs by age and sex.

At age 50, the cumulative incidence of chronic health conditions (of any grade) was 99.9% in CCSs and 96.0% in controls (P<0.0001). The cumulative incidence of grade 3 to 5 chronic health conditions was 96.0% and 84.9%, respectively (P<0.0001).

The cumulative burden for CCSs was 17.1 chronic health conditions, including 4.7 that were grade 3 to 5. For controls, the cumulative burden was 9.2 chronic health conditions, including 2.3 that were grade 3 to 5 (P<0.0001 for both comparisons).

The researchers said second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden observed in CCSs. However, there was “notable heterogeneity” in burden according to the patients’ primary cancer diagnosis.

For instance, growth hormone deficiency was in the top 10th percentile of chronic health conditions for survivors of acute lymphoblastic leukemia but not for controls.

And pulmonary function deficits were in the top 10th percentile for survivors of acute myeloid leukemia and Hodgkin lymphoma but not for controls or survivors of acute lymphoblastic leukemia or non-Hodgkin lymphoma.

“This study found that the average childhood cancer survivor has a cumulative burden of chronic disease that requires a significant time investment by healthcare providers to disentangle and manage—time that community providers are unlikely to have,” Dr Bhakta said.

“The results suggest that childhood cancer survivors may benefit from the integrated, specialized healthcare delivery that is being tried for individuals infected with HIV or those with other complex, chronic health problems.”

Photo courtesy of NIH

Adult survivors of childhood cancer have a greater cumulative burden of chronic health conditions than the general public, according to research published in The Lancet.

The study showed that, by age 50, childhood cancer survivors (CCSs) had experienced, on average, 17.1 chronic health conditions, and matched control subjects had experienced 9.2.

“The cumulative burden of chronic disease revealed in this analysis, along with the complexity and severity of chronic conditions some survivors experience, found childhood cancer survivors to be a vulnerable, medically complex population,” said study author Nickhill Bhakta, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

For this study, Dr Bhakta and his colleagues assessed the lifelong impact of 168 chronic health conditions—such as hepatic, thyroid, ocular, and reproductive disorders—on CCSs and control subjects.

The 3010 evaluable CCSs had survived 10 years or longer from their initial cancer diagnosis and were 18 years or older as of June 30, 2015. The 272 controls had no history of pediatric cancer and were matched to CCSs by age and sex.

At age 50, the cumulative incidence of chronic health conditions (of any grade) was 99.9% in CCSs and 96.0% in controls (P<0.0001). The cumulative incidence of grade 3 to 5 chronic health conditions was 96.0% and 84.9%, respectively (P<0.0001).

The cumulative burden for CCSs was 17.1 chronic health conditions, including 4.7 that were grade 3 to 5. For controls, the cumulative burden was 9.2 chronic health conditions, including 2.3 that were grade 3 to 5 (P<0.0001 for both comparisons).

The researchers said second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden observed in CCSs. However, there was “notable heterogeneity” in burden according to the patients’ primary cancer diagnosis.

For instance, growth hormone deficiency was in the top 10th percentile of chronic health conditions for survivors of acute lymphoblastic leukemia but not for controls.

And pulmonary function deficits were in the top 10th percentile for survivors of acute myeloid leukemia and Hodgkin lymphoma but not for controls or survivors of acute lymphoblastic leukemia or non-Hodgkin lymphoma.

“This study found that the average childhood cancer survivor has a cumulative burden of chronic disease that requires a significant time investment by healthcare providers to disentangle and manage—time that community providers are unlikely to have,” Dr Bhakta said.

“The results suggest that childhood cancer survivors may benefit from the integrated, specialized healthcare delivery that is being tried for individuals infected with HIV or those with other complex, chronic health problems.”

Photo courtesy of NIH

Adult survivors of childhood cancer have a greater cumulative burden of chronic health conditions than the general public, according to research published in The Lancet.

The study showed that, by age 50, childhood cancer survivors (CCSs) had experienced, on average, 17.1 chronic health conditions, and matched control subjects had experienced 9.2.

“The cumulative burden of chronic disease revealed in this analysis, along with the complexity and severity of chronic conditions some survivors experience, found childhood cancer survivors to be a vulnerable, medically complex population,” said study author Nickhill Bhakta, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

For this study, Dr Bhakta and his colleagues assessed the lifelong impact of 168 chronic health conditions—such as hepatic, thyroid, ocular, and reproductive disorders—on CCSs and control subjects.

The 3010 evaluable CCSs had survived 10 years or longer from their initial cancer diagnosis and were 18 years or older as of June 30, 2015. The 272 controls had no history of pediatric cancer and were matched to CCSs by age and sex.

At age 50, the cumulative incidence of chronic health conditions (of any grade) was 99.9% in CCSs and 96.0% in controls (P<0.0001). The cumulative incidence of grade 3 to 5 chronic health conditions was 96.0% and 84.9%, respectively (P<0.0001).

The cumulative burden for CCSs was 17.1 chronic health conditions, including 4.7 that were grade 3 to 5. For controls, the cumulative burden was 9.2 chronic health conditions, including 2.3 that were grade 3 to 5 (P<0.0001 for both comparisons).

The researchers said second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden observed in CCSs. However, there was “notable heterogeneity” in burden according to the patients’ primary cancer diagnosis.

For instance, growth hormone deficiency was in the top 10th percentile of chronic health conditions for survivors of acute lymphoblastic leukemia but not for controls.

And pulmonary function deficits were in the top 10th percentile for survivors of acute myeloid leukemia and Hodgkin lymphoma but not for controls or survivors of acute lymphoblastic leukemia or non-Hodgkin lymphoma.

“This study found that the average childhood cancer survivor has a cumulative burden of chronic disease that requires a significant time investment by healthcare providers to disentangle and manage—time that community providers are unlikely to have,” Dr Bhakta said.

“The results suggest that childhood cancer survivors may benefit from the integrated, specialized healthcare delivery that is being tried for individuals infected with HIV or those with other complex, chronic health problems.”

Rates of opioid prescribing were about 1.2 times higher overall among cancer survivors up to 10 years after diagnosis, compared with matched controls, with more than threefold higher rates of opioid prescriptions for survivors of some cancers, according to a Canadian population-based cohort study.

Searching for the cause of these elevated rates reveals the complexity of the survivorship experience, and may also point the way to areas where there’s work to be done, according to physicians whose practices touch the lives of cancer survivors.

In a retrospective matched cohort study of participants in the Ontario Health Insurance Plan and the Ontario Drug Benefits Program, Rinku Sutradhar, PhD, of the University of Toronto, and her colleagues, identified patients aged 18-64 who had a cancer diagnosis at least 5 years previously. Patients were included only if they had not had a cancer recurrence or another malignancy. When compared 1:1 to age- and sex-matched controls, the 8,601 cancer survivors had a relative rate of opioid prescribing of 1.220 (95% confidence interval [CI], 1.209-1.232), the investigators reported (Cancer 2017 Aug 17. doi: 10.1002/cncr.30839).

Opioid prescribing rates varied according to the type of cancer the survivor had had, with a relative rate of 3.119 for noncolorectal gastrointestinal cancer survivors and a rate of 2.066 for lung cancer survivors. Individuals with nonprostate genitourinary cancers had a prescribing rate of 1.619. All of these differences were statistically significant.

Elevated prescribing rates were not seen in patients with brain, breast, colorectal, head and neck, or prostate cancers. The relative rate of prescribing for hematologic cancers was 1.383, a difference that approached, but did not quite reach, statistical significance (P = .0512).

When multivariable analysis was used to stratify individuals by length of time since cancer diagnosis, a significantly elevated relative rate of opioid prescribing persisted; for those 5-10 years from diagnosis, the relative rate was 1.190 (95% CI, 1.040-1.362, P = .011), while for those diagnosed at least 10 years ago, the relative rate was 1.244 (95% CI, 1.090-1.420; P = .00118).

Multivariable analysis was also used to control for income, rural residence, and comorbidities. However, the study could capture only opioids that were obtained with a prescription, and could not track whether medications were taken by the person for whom they were prescribed, Dr. Sutradhar and her colleagues said.

Cancer survivors may have a higher prevalence of chronic pain than the general population for reasons related both to their initial diagnosis and the sequelae of treatments such as surgery, chemotherapy, and radiation therapy, the investigators noted, adding, “it is also possible that a higher rate of opioid prescribing among survivors is due to a dependency that originated from opioid use earlier in the disease trajectory.”

Because of the potential for opioid use disorder and the many adverse effects that can be associated with long-term opioid use, they said, “primary care providers who treat cancer survivors should be encouraged to critically examine reasons for lingering opioid use among their patients.”

The oncologist’s perspective

Walter M. Stadler, MD, an oncologist who treats genitourinary and hematologic cancers, also wonders whether it’s pain or dependency that’s driving the increased prescribing rates in cancer survivors.

What can primary care offer?

Larissa Nekhlyudov, MD, is an internal medicine physician whose clinical practice straddles two domains. She sees patients, including some cancer survivors, as a primary care provider; she also provides care in a survivorship clinic to adult survivors of childhood cancers. There, she is able to focus more on survivorship care, developing a care plan and communicating with primary care providers about care elements her patients need.

Mental health implications of survivorship

Viewing the issue through the lens of mental health offers a slightly different perspective. Thomas B. Strouse, MD, is a psychiatrist who holds the Maddie Katz Chair in palliative care research and education at the University of California, Los Angeles. He said he laments the current “opioidophobia” that calls into question any long-term opioid prescribing.

Acknowledging that there’s certainly a serious nationwide problem with both prescription and nonprescription opioid abuse, Dr. Strouse said he still finds it unfortunate that the current situation has “reactivated for many people a certain set of reflexes that say that any chronic opioid use is always a bad thing. That’s simply not true,” he said.

“Whether opioids are the right treatment for all of those patients, of course, is an entirely fair question. But it’s unfortunate, or wrong, for everybody to approach this article and to say that we know that for all of these patients, chronic opioid therapy is not appropriate,” he added.

Chronic pain that lingers after cancer treatments affects “a very significant minority of cancer survivors,” he said. It’s also true that the meaning of pain can be different for cancer survivors, said Dr. Strouse. For a cancer survivor, “any new pain is cancer pain until proven otherwise,” he said.

Further, pivoting from the attentive, multidisciplinary, wraparound care often received during cancer treatment to the relatively unsupported survivorship experience can be a rough transition for some. Despite the grim reason for the connection, “frequently, it’s the best experience of patients’ lives from a human relations perspective. … We don’t think enough about the loss that the end of cancer treatment may mean for people who may have otherwise unsatisfactory relationships in their lives,” he said.

Dr. Strouse, who works extensively with cancer survivors, said that the elevated rate of opioid prescribing seen in this study “opens the door to a bigger discussion about the challenges in the relatively empty domain of survivorship.” After discharge from cancer care, patients are all too often left without a navigator to help them through the years when, though their treatment is complete, anxiety, financial and social strain, and pain may linger.

The study, he said, should be a call to physicians for “a more meaningful commitment to understanding the burdens of survivorship, and actually offering meaningful clinical services to those people in an integrated and appropriate way.” This might include determining a patient’s absolute minimum opioid requirement, with a goal of getting the patient off opioids, but also making sure the patient has knowledge of and access to alternative pharmacologic and nonpharmacologic treatments for pain. “That seems like a reasonable approach,” said Dr. Strouse.

None of the study’s authors or the physicians interviewed for commentary had relevant conflicts of interest.

[email protected]

On Twitter @karioakes

Rates of opioid prescribing were about 1.2 times higher overall among cancer survivors up to 10 years after diagnosis, compared with matched controls, with more than threefold higher rates of opioid prescriptions for survivors of some cancers, according to a Canadian population-based cohort study.

Searching for the cause of these elevated rates reveals the complexity of the survivorship experience, and may also point the way to areas where there’s work to be done, according to physicians whose practices touch the lives of cancer survivors.

In a retrospective matched cohort study of participants in the Ontario Health Insurance Plan and the Ontario Drug Benefits Program, Rinku Sutradhar, PhD, of the University of Toronto, and her colleagues, identified patients aged 18-64 who had a cancer diagnosis at least 5 years previously. Patients were included only if they had not had a cancer recurrence or another malignancy. When compared 1:1 to age- and sex-matched controls, the 8,601 cancer survivors had a relative rate of opioid prescribing of 1.220 (95% confidence interval [CI], 1.209-1.232), the investigators reported (Cancer 2017 Aug 17. doi: 10.1002/cncr.30839).

Opioid prescribing rates varied according to the type of cancer the survivor had had, with a relative rate of 3.119 for noncolorectal gastrointestinal cancer survivors and a rate of 2.066 for lung cancer survivors. Individuals with nonprostate genitourinary cancers had a prescribing rate of 1.619. All of these differences were statistically significant.

Elevated prescribing rates were not seen in patients with brain, breast, colorectal, head and neck, or prostate cancers. The relative rate of prescribing for hematologic cancers was 1.383, a difference that approached, but did not quite reach, statistical significance (P = .0512).

When multivariable analysis was used to stratify individuals by length of time since cancer diagnosis, a significantly elevated relative rate of opioid prescribing persisted; for those 5-10 years from diagnosis, the relative rate was 1.190 (95% CI, 1.040-1.362, P = .011), while for those diagnosed at least 10 years ago, the relative rate was 1.244 (95% CI, 1.090-1.420; P = .00118).

Multivariable analysis was also used to control for income, rural residence, and comorbidities. However, the study could capture only opioids that were obtained with a prescription, and could not track whether medications were taken by the person for whom they were prescribed, Dr. Sutradhar and her colleagues said.

Cancer survivors may have a higher prevalence of chronic pain than the general population for reasons related both to their initial diagnosis and the sequelae of treatments such as surgery, chemotherapy, and radiation therapy, the investigators noted, adding, “it is also possible that a higher rate of opioid prescribing among survivors is due to a dependency that originated from opioid use earlier in the disease trajectory.”

Because of the potential for opioid use disorder and the many adverse effects that can be associated with long-term opioid use, they said, “primary care providers who treat cancer survivors should be encouraged to critically examine reasons for lingering opioid use among their patients.”

The oncologist’s perspective

Walter M. Stadler, MD, an oncologist who treats genitourinary and hematologic cancers, also wonders whether it’s pain or dependency that’s driving the increased prescribing rates in cancer survivors.

What can primary care offer?

Larissa Nekhlyudov, MD, is an internal medicine physician whose clinical practice straddles two domains. She sees patients, including some cancer survivors, as a primary care provider; she also provides care in a survivorship clinic to adult survivors of childhood cancers. There, she is able to focus more on survivorship care, developing a care plan and communicating with primary care providers about care elements her patients need.

Mental health implications of survivorship

Viewing the issue through the lens of mental health offers a slightly different perspective. Thomas B. Strouse, MD, is a psychiatrist who holds the Maddie Katz Chair in palliative care research and education at the University of California, Los Angeles. He said he laments the current “opioidophobia” that calls into question any long-term opioid prescribing.

Acknowledging that there’s certainly a serious nationwide problem with both prescription and nonprescription opioid abuse, Dr. Strouse said he still finds it unfortunate that the current situation has “reactivated for many people a certain set of reflexes that say that any chronic opioid use is always a bad thing. That’s simply not true,” he said.

“Whether opioids are the right treatment for all of those patients, of course, is an entirely fair question. But it’s unfortunate, or wrong, for everybody to approach this article and to say that we know that for all of these patients, chronic opioid therapy is not appropriate,” he added.

Chronic pain that lingers after cancer treatments affects “a very significant minority of cancer survivors,” he said. It’s also true that the meaning of pain can be different for cancer survivors, said Dr. Strouse. For a cancer survivor, “any new pain is cancer pain until proven otherwise,” he said.

Further, pivoting from the attentive, multidisciplinary, wraparound care often received during cancer treatment to the relatively unsupported survivorship experience can be a rough transition for some. Despite the grim reason for the connection, “frequently, it’s the best experience of patients’ lives from a human relations perspective. … We don’t think enough about the loss that the end of cancer treatment may mean for people who may have otherwise unsatisfactory relationships in their lives,” he said.

Dr. Strouse, who works extensively with cancer survivors, said that the elevated rate of opioid prescribing seen in this study “opens the door to a bigger discussion about the challenges in the relatively empty domain of survivorship.” After discharge from cancer care, patients are all too often left without a navigator to help them through the years when, though their treatment is complete, anxiety, financial and social strain, and pain may linger.

The study, he said, should be a call to physicians for “a more meaningful commitment to understanding the burdens of survivorship, and actually offering meaningful clinical services to those people in an integrated and appropriate way.” This might include determining a patient’s absolute minimum opioid requirement, with a goal of getting the patient off opioids, but also making sure the patient has knowledge of and access to alternative pharmacologic and nonpharmacologic treatments for pain. “That seems like a reasonable approach,” said Dr. Strouse.

None of the study’s authors or the physicians interviewed for commentary had relevant conflicts of interest.

[email protected]

On Twitter @karioakes

Rates of opioid prescribing were about 1.2 times higher overall among cancer survivors up to 10 years after diagnosis, compared with matched controls, with more than threefold higher rates of opioid prescriptions for survivors of some cancers, according to a Canadian population-based cohort study.

Searching for the cause of these elevated rates reveals the complexity of the survivorship experience, and may also point the way to areas where there’s work to be done, according to physicians whose practices touch the lives of cancer survivors.

In a retrospective matched cohort study of participants in the Ontario Health Insurance Plan and the Ontario Drug Benefits Program, Rinku Sutradhar, PhD, of the University of Toronto, and her colleagues, identified patients aged 18-64 who had a cancer diagnosis at least 5 years previously. Patients were included only if they had not had a cancer recurrence or another malignancy. When compared 1:1 to age- and sex-matched controls, the 8,601 cancer survivors had a relative rate of opioid prescribing of 1.220 (95% confidence interval [CI], 1.209-1.232), the investigators reported (Cancer 2017 Aug 17. doi: 10.1002/cncr.30839).

Opioid prescribing rates varied according to the type of cancer the survivor had had, with a relative rate of 3.119 for noncolorectal gastrointestinal cancer survivors and a rate of 2.066 for lung cancer survivors. Individuals with nonprostate genitourinary cancers had a prescribing rate of 1.619. All of these differences were statistically significant.

Elevated prescribing rates were not seen in patients with brain, breast, colorectal, head and neck, or prostate cancers. The relative rate of prescribing for hematologic cancers was 1.383, a difference that approached, but did not quite reach, statistical significance (P = .0512).

When multivariable analysis was used to stratify individuals by length of time since cancer diagnosis, a significantly elevated relative rate of opioid prescribing persisted; for those 5-10 years from diagnosis, the relative rate was 1.190 (95% CI, 1.040-1.362, P = .011), while for those diagnosed at least 10 years ago, the relative rate was 1.244 (95% CI, 1.090-1.420; P = .00118).

Multivariable analysis was also used to control for income, rural residence, and comorbidities. However, the study could capture only opioids that were obtained with a prescription, and could not track whether medications were taken by the person for whom they were prescribed, Dr. Sutradhar and her colleagues said.

Cancer survivors may have a higher prevalence of chronic pain than the general population for reasons related both to their initial diagnosis and the sequelae of treatments such as surgery, chemotherapy, and radiation therapy, the investigators noted, adding, “it is also possible that a higher rate of opioid prescribing among survivors is due to a dependency that originated from opioid use earlier in the disease trajectory.”

Because of the potential for opioid use disorder and the many adverse effects that can be associated with long-term opioid use, they said, “primary care providers who treat cancer survivors should be encouraged to critically examine reasons for lingering opioid use among their patients.”

The oncologist’s perspective

Walter M. Stadler, MD, an oncologist who treats genitourinary and hematologic cancers, also wonders whether it’s pain or dependency that’s driving the increased prescribing rates in cancer survivors.

What can primary care offer?

Larissa Nekhlyudov, MD, is an internal medicine physician whose clinical practice straddles two domains. She sees patients, including some cancer survivors, as a primary care provider; she also provides care in a survivorship clinic to adult survivors of childhood cancers. There, she is able to focus more on survivorship care, developing a care plan and communicating with primary care providers about care elements her patients need.

Mental health implications of survivorship

Viewing the issue through the lens of mental health offers a slightly different perspective. Thomas B. Strouse, MD, is a psychiatrist who holds the Maddie Katz Chair in palliative care research and education at the University of California, Los Angeles. He said he laments the current “opioidophobia” that calls into question any long-term opioid prescribing.

Acknowledging that there’s certainly a serious nationwide problem with both prescription and nonprescription opioid abuse, Dr. Strouse said he still finds it unfortunate that the current situation has “reactivated for many people a certain set of reflexes that say that any chronic opioid use is always a bad thing. That’s simply not true,” he said.

“Whether opioids are the right treatment for all of those patients, of course, is an entirely fair question. But it’s unfortunate, or wrong, for everybody to approach this article and to say that we know that for all of these patients, chronic opioid therapy is not appropriate,” he added.

Chronic pain that lingers after cancer treatments affects “a very significant minority of cancer survivors,” he said. It’s also true that the meaning of pain can be different for cancer survivors, said Dr. Strouse. For a cancer survivor, “any new pain is cancer pain until proven otherwise,” he said.

Further, pivoting from the attentive, multidisciplinary, wraparound care often received during cancer treatment to the relatively unsupported survivorship experience can be a rough transition for some. Despite the grim reason for the connection, “frequently, it’s the best experience of patients’ lives from a human relations perspective. … We don’t think enough about the loss that the end of cancer treatment may mean for people who may have otherwise unsatisfactory relationships in their lives,” he said.

Dr. Strouse, who works extensively with cancer survivors, said that the elevated rate of opioid prescribing seen in this study “opens the door to a bigger discussion about the challenges in the relatively empty domain of survivorship.” After discharge from cancer care, patients are all too often left without a navigator to help them through the years when, though their treatment is complete, anxiety, financial and social strain, and pain may linger.

The study, he said, should be a call to physicians for “a more meaningful commitment to understanding the burdens of survivorship, and actually offering meaningful clinical services to those people in an integrated and appropriate way.” This might include determining a patient’s absolute minimum opioid requirement, with a goal of getting the patient off opioids, but also making sure the patient has knowledge of and access to alternative pharmacologic and nonpharmacologic treatments for pain. “That seems like a reasonable approach,” said Dr. Strouse.

None of the study’s authors or the physicians interviewed for commentary had relevant conflicts of interest.

[email protected]

On Twitter @karioakes

Three percent of patients developed immune-related adverse neurologic events within 12 months of receiving nivolumab or pembrolizumab, according to the results of a single-center retrospective study.

These syndromes included myopathy, axonal thoracolumbar polyradiculopathy, severe demyelinating length-dependent peripheral neuropathy with axonal loss, a facial diplegic variant of Guillain-Barré syndrome, asymmetric vasculitic neuropathy, cerebellar ataxia with dysarthria, autoimmune retinopathy, bilateral internuclear ophthalmoplegia, and headache, reported Justin C. Kao, MD, of Mayo Clinic, Rochester, Minn., and his coinvestigators. Most patients improved after stopping treatment and starting corticosteroids, but one patient developed necrotizing myopathy and died after withdrawal of ventilator support.

Nivolumab and pembrolizumab, which inhibit the programmed death–1 (PD-1) receptor, are approved for treating metastatic melanoma, non–small-cell lung cancer, renal cell carcinoma, Hodgkin lymphoma, head and neck cancers, and urothelial carcinoma. In response to a surge in reports of neurologic events associated with anti–PD-1 therapy, the investigators searched the Mayo Clinic pharmacy database and identified 347 patients treated with pembrolizumab or nivolumab between 2014 and 2016. Ten patients (2.9%) developed neurologic complications within 12 months of anti–PD-1 exposure, including eight men and two women. The median age was 71 years. None of their neurologic symptoms could be directly attributed to other treatments or to metastatic disease. Most had mild to moderate disability, with modified Rankin Scale (mRS) scores of 2, and symptom severity peaked between 1 day and more than 3 months after starting anti–PD-1 treatment (JAMA Neurol. 2017 Sep 5. doi: 10.1001/jamaneurol.2017.1912).

Stopping anti–PD-1 treatment and starting high-dose corticosteroids led to substantial neurologic improvements (mRS scores, 0-3), except in the case of fatal necrotizing myopathy, the researchers said. That patient, who was receiving pembrolizumab for stage 4 melanoma, developed extraocular, bulbar, and proximal limb girdle weakness that worsened over a period of 3 weeks and did not respond to prednisone (80 mg daily) or to three sessions of plasmapheresis.

If a patient on anti–PD-1 therapy develops neurologic symptoms, clinicians should promptly stop treatment and pursue a full work-up, including electrodiagnostic studies and consideration of muscle or nerve biopsy to clarify underlying pathophysiologic mechanisms, the researchers said. “If the clinical examination demonstrates severe clinical deficits at onset or worsens despite medication discontinuation, additional immune suppressant treatment should be considered,” they said. They recommended prednisone (1 mg/kg) with a taper over a 1-month period. Intravenous immunoglobulin therapy or plasma exchange may be warranted if patients continue to worsen, they said.

The investigators did not report external funding sources. Mr. Kao had no disclosures. Two coinvestigators disclosed ties to the American Association of Neuromuscular & Electrodiagnostic Medicine, the American Academy of Neurology, the Continuum: Lifelong Learning in Neurology, Ionis Pharmaceuticals, Alnylam, and Oxford University Press. The remaining coinvestigators reported having no conflicts of interest.

Three percent of patients developed immune-related adverse neurologic events within 12 months of receiving nivolumab or pembrolizumab, according to the results of a single-center retrospective study.

These syndromes included myopathy, axonal thoracolumbar polyradiculopathy, severe demyelinating length-dependent peripheral neuropathy with axonal loss, a facial diplegic variant of Guillain-Barré syndrome, asymmetric vasculitic neuropathy, cerebellar ataxia with dysarthria, autoimmune retinopathy, bilateral internuclear ophthalmoplegia, and headache, reported Justin C. Kao, MD, of Mayo Clinic, Rochester, Minn., and his coinvestigators. Most patients improved after stopping treatment and starting corticosteroids, but one patient developed necrotizing myopathy and died after withdrawal of ventilator support.

Nivolumab and pembrolizumab, which inhibit the programmed death–1 (PD-1) receptor, are approved for treating metastatic melanoma, non–small-cell lung cancer, renal cell carcinoma, Hodgkin lymphoma, head and neck cancers, and urothelial carcinoma. In response to a surge in reports of neurologic events associated with anti–PD-1 therapy, the investigators searched the Mayo Clinic pharmacy database and identified 347 patients treated with pembrolizumab or nivolumab between 2014 and 2016. Ten patients (2.9%) developed neurologic complications within 12 months of anti–PD-1 exposure, including eight men and two women. The median age was 71 years. None of their neurologic symptoms could be directly attributed to other treatments or to metastatic disease. Most had mild to moderate disability, with modified Rankin Scale (mRS) scores of 2, and symptom severity peaked between 1 day and more than 3 months after starting anti–PD-1 treatment (JAMA Neurol. 2017 Sep 5. doi: 10.1001/jamaneurol.2017.1912).

Stopping anti–PD-1 treatment and starting high-dose corticosteroids led to substantial neurologic improvements (mRS scores, 0-3), except in the case of fatal necrotizing myopathy, the researchers said. That patient, who was receiving pembrolizumab for stage 4 melanoma, developed extraocular, bulbar, and proximal limb girdle weakness that worsened over a period of 3 weeks and did not respond to prednisone (80 mg daily) or to three sessions of plasmapheresis.

If a patient on anti–PD-1 therapy develops neurologic symptoms, clinicians should promptly stop treatment and pursue a full work-up, including electrodiagnostic studies and consideration of muscle or nerve biopsy to clarify underlying pathophysiologic mechanisms, the researchers said. “If the clinical examination demonstrates severe clinical deficits at onset or worsens despite medication discontinuation, additional immune suppressant treatment should be considered,” they said. They recommended prednisone (1 mg/kg) with a taper over a 1-month period. Intravenous immunoglobulin therapy or plasma exchange may be warranted if patients continue to worsen, they said.

The investigators did not report external funding sources. Mr. Kao had no disclosures. Two coinvestigators disclosed ties to the American Association of Neuromuscular & Electrodiagnostic Medicine, the American Academy of Neurology, the Continuum: Lifelong Learning in Neurology, Ionis Pharmaceuticals, Alnylam, and Oxford University Press. The remaining coinvestigators reported having no conflicts of interest.

Three percent of patients developed immune-related adverse neurologic events within 12 months of receiving nivolumab or pembrolizumab, according to the results of a single-center retrospective study.

These syndromes included myopathy, axonal thoracolumbar polyradiculopathy, severe demyelinating length-dependent peripheral neuropathy with axonal loss, a facial diplegic variant of Guillain-Barré syndrome, asymmetric vasculitic neuropathy, cerebellar ataxia with dysarthria, autoimmune retinopathy, bilateral internuclear ophthalmoplegia, and headache, reported Justin C. Kao, MD, of Mayo Clinic, Rochester, Minn., and his coinvestigators. Most patients improved after stopping treatment and starting corticosteroids, but one patient developed necrotizing myopathy and died after withdrawal of ventilator support.

Nivolumab and pembrolizumab, which inhibit the programmed death–1 (PD-1) receptor, are approved for treating metastatic melanoma, non–small-cell lung cancer, renal cell carcinoma, Hodgkin lymphoma, head and neck cancers, and urothelial carcinoma. In response to a surge in reports of neurologic events associated with anti–PD-1 therapy, the investigators searched the Mayo Clinic pharmacy database and identified 347 patients treated with pembrolizumab or nivolumab between 2014 and 2016. Ten patients (2.9%) developed neurologic complications within 12 months of anti–PD-1 exposure, including eight men and two women. The median age was 71 years. None of their neurologic symptoms could be directly attributed to other treatments or to metastatic disease. Most had mild to moderate disability, with modified Rankin Scale (mRS) scores of 2, and symptom severity peaked between 1 day and more than 3 months after starting anti–PD-1 treatment (JAMA Neurol. 2017 Sep 5. doi: 10.1001/jamaneurol.2017.1912).

Stopping anti–PD-1 treatment and starting high-dose corticosteroids led to substantial neurologic improvements (mRS scores, 0-3), except in the case of fatal necrotizing myopathy, the researchers said. That patient, who was receiving pembrolizumab for stage 4 melanoma, developed extraocular, bulbar, and proximal limb girdle weakness that worsened over a period of 3 weeks and did not respond to prednisone (80 mg daily) or to three sessions of plasmapheresis.

If a patient on anti–PD-1 therapy develops neurologic symptoms, clinicians should promptly stop treatment and pursue a full work-up, including electrodiagnostic studies and consideration of muscle or nerve biopsy to clarify underlying pathophysiologic mechanisms, the researchers said. “If the clinical examination demonstrates severe clinical deficits at onset or worsens despite medication discontinuation, additional immune suppressant treatment should be considered,” they said. They recommended prednisone (1 mg/kg) with a taper over a 1-month period. Intravenous immunoglobulin therapy or plasma exchange may be warranted if patients continue to worsen, they said.

The investigators did not report external funding sources. Mr. Kao had no disclosures. Two coinvestigators disclosed ties to the American Association of Neuromuscular & Electrodiagnostic Medicine, the American Academy of Neurology, the Continuum: Lifelong Learning in Neurology, Ionis Pharmaceuticals, Alnylam, and Oxford University Press. The remaining coinvestigators reported having no conflicts of interest.

Photo by Bill Branson

New research suggests survivors of childhood cancer can incur high out-of-pocket medical costs into adulthood and may forgo healthcare to lessen this financial burden.

The study showed that childhood cancer survivors (CCSs) were more likely than non-CCSs to have out-of-pocket medical costs that were at least 10% of their annual income.

And these high costs were associated with delaying care or skipping it altogether.

These findings were published in the Journal of Clinical Oncology.

“Survivors who reported spending a higher percentage of their income on out-of-pocket medical costs were not only more likely to report financial burden, they also were at risk for undertaking behaviors potentially detrimental to their health in order to save money,” said study author Ryan Nipp, MD, of Massachusetts General Hospital Cancer Center in Boston.

“While studies have identified associations between financial burden and patients’ treatment outcomes, quality of life, and even survival among adults with cancer, as far as we know, this is the first to report these associations in survivors of childhood cancer.”

For this research, Dr Nipp and his colleagues surveyed participants in the Childhood Cancer Survivor Study. This included adults who had been treated for childhood cancers between 1970 and 1986 along with a control group of siblings not affected by cancer.

In 2011 and 2012, participants were asked to provide information about their health insurance, the out-of-pocket healthcare costs they paid during the previous year, and sociodemographic information such as annual income and employment status.

The researchers also asked participants whether medical costs posed a financial burden and, if so, what measures they had taken to deal with that burden.

Study population

The researchers received complete responses from 580 CCSs and 173 of their siblings without a history of cancer. The most common cancer diagnosis was leukemia (33%), followed by Hodgkin lymphoma (14%), while non-Hodgkin lymphoma was less common (7%).

CCSs were a mean of 30.2 years from diagnosis. Use of chemotherapy (77%), radiation (66%), and surgery (81%) were common. Few patients had cancer recurrence (13%) or second cancers (5%).

There was no significant difference between CCSs and their siblings with regard to age at the time of the survey (P=0.071), household income (P=0.053), education (P=0.345), health insurance status (P=0.317), or having at least 1 hospitalization in the past year (P=0.270).

However, CCSs were significantly more likely than siblings to have chronic health conditions (P<0.001). Forty percent of CCSs had severe or life-threatening chronic conditions, compared to 17% of siblings.

Seventy-six percent of CCSs and 80% of siblings were employed. Twenty-nine percent of CCSs and 39% of siblings had household incomes exceeding $100,000. Twelve percent of CCSs and 5% of siblings had household incomes below $20,000.

Ninety-one percent of CCSs and 93% of siblings were insured. Most subjects in both groups (81% and 87%, respectively) had employer-sponsored insurance.

Results

CCSs were significantly more likely than their siblings to have out-of-pocket medical costs that were at least 10% of their annual income—10% and 3%, respectively (P<0.001).

Among CCSs, those with higher out-of-pocket costs (≥10% vs <10% of income) were more likely to have household incomes below $50,000 (odds ratio [OR]=5.5) and to report being hospitalized in the past year (OR=2.3).

CCSs with a higher percentage of their income spent on out-of-pocket costs were also more likely to:

• Have problems paying their medical bills (OR=8.8)
• Report inability to pay for basic costs of living such as food, heat, or rent (OR=6.1)
• Defer healthcare for a medical problem (OR=3.1)
• Skip a test, treatment, or follow-up (OR=2.1)
• Consider filing for bankruptcy (OR=6.4).

“A more comprehensive understanding of the relationship between high out-of-pocket medical costs and the adverse effects of increased financial burden on cancer survivors could be instrumental in helping us identify those at risk for higher costs to help us address their financial challenges and improve health outcomes,” Dr Nipp said.

“It could also help inform policy changes to help meet the unique needs of cancer survivors and improve our understanding of how both higher costs and resulting financial burden influence patients’ approach to their medical care and decision-making.”

Photo by Bill Branson

New research suggests survivors of childhood cancer can incur high out-of-pocket medical costs into adulthood and may forgo healthcare to lessen this financial burden.

The study showed that childhood cancer survivors (CCSs) were more likely than non-CCSs to have out-of-pocket medical costs that were at least 10% of their annual income.

And these high costs were associated with delaying care or skipping it altogether.

These findings were published in the Journal of Clinical Oncology.

“Survivors who reported spending a higher percentage of their income on out-of-pocket medical costs were not only more likely to report financial burden, they also were at risk for undertaking behaviors potentially detrimental to their health in order to save money,” said study author Ryan Nipp, MD, of Massachusetts General Hospital Cancer Center in Boston.

“While studies have identified associations between financial burden and patients’ treatment outcomes, quality of life, and even survival among adults with cancer, as far as we know, this is the first to report these associations in survivors of childhood cancer.”

For this research, Dr Nipp and his colleagues surveyed participants in the Childhood Cancer Survivor Study. This included adults who had been treated for childhood cancers between 1970 and 1986 along with a control group of siblings not affected by cancer.

In 2011 and 2012, participants were asked to provide information about their health insurance, the out-of-pocket healthcare costs they paid during the previous year, and sociodemographic information such as annual income and employment status.

The researchers also asked participants whether medical costs posed a financial burden and, if so, what measures they had taken to deal with that burden.

Study population

The researchers received complete responses from 580 CCSs and 173 of their siblings without a history of cancer. The most common cancer diagnosis was leukemia (33%), followed by Hodgkin lymphoma (14%), while non-Hodgkin lymphoma was less common (7%).

CCSs were a mean of 30.2 years from diagnosis. Use of chemotherapy (77%), radiation (66%), and surgery (81%) were common. Few patients had cancer recurrence (13%) or second cancers (5%).

There was no significant difference between CCSs and their siblings with regard to age at the time of the survey (P=0.071), household income (P=0.053), education (P=0.345), health insurance status (P=0.317), or having at least 1 hospitalization in the past year (P=0.270).

However, CCSs were significantly more likely than siblings to have chronic health conditions (P<0.001). Forty percent of CCSs had severe or life-threatening chronic conditions, compared to 17% of siblings.

Seventy-six percent of CCSs and 80% of siblings were employed. Twenty-nine percent of CCSs and 39% of siblings had household incomes exceeding $100,000. Twelve percent of CCSs and 5% of siblings had household incomes below $20,000.

Ninety-one percent of CCSs and 93% of siblings were insured. Most subjects in both groups (81% and 87%, respectively) had employer-sponsored insurance.

Results

CCSs were significantly more likely than their siblings to have out-of-pocket medical costs that were at least 10% of their annual income—10% and 3%, respectively (P<0.001).

Among CCSs, those with higher out-of-pocket costs (≥10% vs <10% of income) were more likely to have household incomes below $50,000 (odds ratio [OR]=5.5) and to report being hospitalized in the past year (OR=2.3).

CCSs with a higher percentage of their income spent on out-of-pocket costs were also more likely to:

• Have problems paying their medical bills (OR=8.8)
• Report inability to pay for basic costs of living such as food, heat, or rent (OR=6.1)
• Defer healthcare for a medical problem (OR=3.1)
• Skip a test, treatment, or follow-up (OR=2.1)
• Consider filing for bankruptcy (OR=6.4).

“A more comprehensive understanding of the relationship between high out-of-pocket medical costs and the adverse effects of increased financial burden on cancer survivors could be instrumental in helping us identify those at risk for higher costs to help us address their financial challenges and improve health outcomes,” Dr Nipp said.

“It could also help inform policy changes to help meet the unique needs of cancer survivors and improve our understanding of how both higher costs and resulting financial burden influence patients’ approach to their medical care and decision-making.”

Photo by Bill Branson

New research suggests survivors of childhood cancer can incur high out-of-pocket medical costs into adulthood and may forgo healthcare to lessen this financial burden.

The study showed that childhood cancer survivors (CCSs) were more likely than non-CCSs to have out-of-pocket medical costs that were at least 10% of their annual income.

And these high costs were associated with delaying care or skipping it altogether.

These findings were published in the Journal of Clinical Oncology.

“Survivors who reported spending a higher percentage of their income on out-of-pocket medical costs were not only more likely to report financial burden, they also were at risk for undertaking behaviors potentially detrimental to their health in order to save money,” said study author Ryan Nipp, MD, of Massachusetts General Hospital Cancer Center in Boston.

“While studies have identified associations between financial burden and patients’ treatment outcomes, quality of life, and even survival among adults with cancer, as far as we know, this is the first to report these associations in survivors of childhood cancer.”

For this research, Dr Nipp and his colleagues surveyed participants in the Childhood Cancer Survivor Study. This included adults who had been treated for childhood cancers between 1970 and 1986 along with a control group of siblings not affected by cancer.

In 2011 and 2012, participants were asked to provide information about their health insurance, the out-of-pocket healthcare costs they paid during the previous year, and sociodemographic information such as annual income and employment status.

The researchers also asked participants whether medical costs posed a financial burden and, if so, what measures they had taken to deal with that burden.

Study population

The researchers received complete responses from 580 CCSs and 173 of their siblings without a history of cancer. The most common cancer diagnosis was leukemia (33%), followed by Hodgkin lymphoma (14%), while non-Hodgkin lymphoma was less common (7%).

CCSs were a mean of 30.2 years from diagnosis. Use of chemotherapy (77%), radiation (66%), and surgery (81%) were common. Few patients had cancer recurrence (13%) or second cancers (5%).

There was no significant difference between CCSs and their siblings with regard to age at the time of the survey (P=0.071), household income (P=0.053), education (P=0.345), health insurance status (P=0.317), or having at least 1 hospitalization in the past year (P=0.270).

However, CCSs were significantly more likely than siblings to have chronic health conditions (P<0.001). Forty percent of CCSs had severe or life-threatening chronic conditions, compared to 17% of siblings.

Seventy-six percent of CCSs and 80% of siblings were employed. Twenty-nine percent of CCSs and 39% of siblings had household incomes exceeding $100,000. Twelve percent of CCSs and 5% of siblings had household incomes below $20,000.

Ninety-one percent of CCSs and 93% of siblings were insured. Most subjects in both groups (81% and 87%, respectively) had employer-sponsored insurance.

Results

CCSs were significantly more likely than their siblings to have out-of-pocket medical costs that were at least 10% of their annual income—10% and 3%, respectively (P<0.001).

Among CCSs, those with higher out-of-pocket costs (≥10% vs <10% of income) were more likely to have household incomes below $50,000 (odds ratio [OR]=5.5) and to report being hospitalized in the past year (OR=2.3).

CCSs with a higher percentage of their income spent on out-of-pocket costs were also more likely to:

• Have problems paying their medical bills (OR=8.8)
• Report inability to pay for basic costs of living such as food, heat, or rent (OR=6.1)
• Defer healthcare for a medical problem (OR=3.1)
• Skip a test, treatment, or follow-up (OR=2.1)
• Consider filing for bankruptcy (OR=6.4).

“A more comprehensive understanding of the relationship between high out-of-pocket medical costs and the adverse effects of increased financial burden on cancer survivors could be instrumental in helping us identify those at risk for higher costs to help us address their financial challenges and improve health outcomes,” Dr Nipp said.

“It could also help inform policy changes to help meet the unique needs of cancer survivors and improve our understanding of how both higher costs and resulting financial burden influence patients’ approach to their medical care and decision-making.”

Photo from Business Wire

Health Canada has issued a non-conditional marketing authorization for brentuximab vedotin (Adcetris).

This means the drug is now approved for use as consolidation after autologous stem cell transplant (ASCT) in patients with Hodgkin lymphoma (HL) who have an increased risk of relapse or progression.

Brentuximab vedotin previously received approval with conditions in Canada to treat HL patients who relapse after ASCT or HL patients who are not ASCT candidates and relapse after at least 2 multi-agent chemotherapy regimens.

Brentuximab vedotin also has conditional approval in Canada to treat patients with systemic anaplastic large-cell lymphoma who relapse after at least 1 multi-agent chemotherapy regimen.

Brentuximab vedotin is an antibody-drug conjugate consisting of an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E.

Brentuximab vedotin has marketing authorization in 67 countries for the treatment of relapsed or refractory HL and systemic anaplastic large-cell lymphoma.

Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights, and Takeda has rights to commercialize the drug in the rest of the world.

AETHERA trial

Health Canada’s decision to extend the marketing authorization of brentuximab vedotin is based on results from the phase 3 AETHERA trial.

The trial was designed to compare brentuximab vedotin to placebo, both administered for up to 16 cycles (approximately 1 year) every 3 weeks following ASCT. Results from the trial were published in The Lancet in March 2015.

The study enrolled 329 HL patients at risk of relapse or progression—165 on the brentuximab vedotin arm and 164 on the placebo arm.

Patients were eligible for enrollment if they had a history of primary refractory HL, relapsed within a year of receiving frontline chemotherapy, and/or had disease outside of the lymph nodes at the time of pre-ASCT relapse.

Brentuximab vedotin conferred a significant increase in progression-free survival over placebo, with a hazard ratio of 0.57 (P=0.001). The median progression-free survival was 43 months for patients who received brentuximab vedotin and 24 months for those who received placebo.

The most common adverse events (≥20%), of any grade and regardless of causality, in the brentuximab vedotin arm were neutropenia (78%), peripheral sensory neuropathy (56%), thrombocytopenia (41%), anemia (27%), upper respiratory tract infection (26%), fatigue (24%), peripheral motor neuropathy (23%), nausea (22%), cough (21%), and diarrhea (20%).

The most common adverse events (≥20%), of any grade and regardless of causality, in the placebo arm were neutropenia (34%), upper respiratory tract infection (23%), and thrombocytopenia (20%).

In all, 67% of patients on the brentuximab vedotin arm experienced peripheral neuropathy. Of those patients, 85% had resolution (59%) or partial improvement (26%) in symptoms at the time of their last evaluation, with a median time to improvement of 23 weeks (range, 0.1-138).

Photo from Business Wire

Health Canada has issued a non-conditional marketing authorization for brentuximab vedotin (Adcetris).

This means the drug is now approved for use as consolidation after autologous stem cell transplant (ASCT) in patients with Hodgkin lymphoma (HL) who have an increased risk of relapse or progression.

Brentuximab vedotin previously received approval with conditions in Canada to treat HL patients who relapse after ASCT or HL patients who are not ASCT candidates and relapse after at least 2 multi-agent chemotherapy regimens.

Brentuximab vedotin also has conditional approval in Canada to treat patients with systemic anaplastic large-cell lymphoma who relapse after at least 1 multi-agent chemotherapy regimen.

Brentuximab vedotin is an antibody-drug conjugate consisting of an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E.

Brentuximab vedotin has marketing authorization in 67 countries for the treatment of relapsed or refractory HL and systemic anaplastic large-cell lymphoma.

Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights, and Takeda has rights to commercialize the drug in the rest of the world.

AETHERA trial

Health Canada’s decision to extend the marketing authorization of brentuximab vedotin is based on results from the phase 3 AETHERA trial.

The trial was designed to compare brentuximab vedotin to placebo, both administered for up to 16 cycles (approximately 1 year) every 3 weeks following ASCT. Results from the trial were published in The Lancet in March 2015.

The study enrolled 329 HL patients at risk of relapse or progression—165 on the brentuximab vedotin arm and 164 on the placebo arm.

Patients were eligible for enrollment if they had a history of primary refractory HL, relapsed within a year of receiving frontline chemotherapy, and/or had disease outside of the lymph nodes at the time of pre-ASCT relapse.

Brentuximab vedotin conferred a significant increase in progression-free survival over placebo, with a hazard ratio of 0.57 (P=0.001). The median progression-free survival was 43 months for patients who received brentuximab vedotin and 24 months for those who received placebo.

The most common adverse events (≥20%), of any grade and regardless of causality, in the brentuximab vedotin arm were neutropenia (78%), peripheral sensory neuropathy (56%), thrombocytopenia (41%), anemia (27%), upper respiratory tract infection (26%), fatigue (24%), peripheral motor neuropathy (23%), nausea (22%), cough (21%), and diarrhea (20%).

The most common adverse events (≥20%), of any grade and regardless of causality, in the placebo arm were neutropenia (34%), upper respiratory tract infection (23%), and thrombocytopenia (20%).

In all, 67% of patients on the brentuximab vedotin arm experienced peripheral neuropathy. Of those patients, 85% had resolution (59%) or partial improvement (26%) in symptoms at the time of their last evaluation, with a median time to improvement of 23 weeks (range, 0.1-138).

Photo from Business Wire

Health Canada has issued a non-conditional marketing authorization for brentuximab vedotin (Adcetris).

This means the drug is now approved for use as consolidation after autologous stem cell transplant (ASCT) in patients with Hodgkin lymphoma (HL) who have an increased risk of relapse or progression.

Brentuximab vedotin previously received approval with conditions in Canada to treat HL patients who relapse after ASCT or HL patients who are not ASCT candidates and relapse after at least 2 multi-agent chemotherapy regimens.

Brentuximab vedotin also has conditional approval in Canada to treat patients with systemic anaplastic large-cell lymphoma who relapse after at least 1 multi-agent chemotherapy regimen.

Brentuximab vedotin is an antibody-drug conjugate consisting of an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E.

Brentuximab vedotin has marketing authorization in 67 countries for the treatment of relapsed or refractory HL and systemic anaplastic large-cell lymphoma.

Seattle Genetics and Takeda are jointly developing brentuximab vedotin. Seattle Genetics has US and Canadian commercialization rights, and Takeda has rights to commercialize the drug in the rest of the world.

AETHERA trial

Health Canada’s decision to extend the marketing authorization of brentuximab vedotin is based on results from the phase 3 AETHERA trial.

The trial was designed to compare brentuximab vedotin to placebo, both administered for up to 16 cycles (approximately 1 year) every 3 weeks following ASCT. Results from the trial were published in The Lancet in March 2015.

The study enrolled 329 HL patients at risk of relapse or progression—165 on the brentuximab vedotin arm and 164 on the placebo arm.

Patients were eligible for enrollment if they had a history of primary refractory HL, relapsed within a year of receiving frontline chemotherapy, and/or had disease outside of the lymph nodes at the time of pre-ASCT relapse.

Brentuximab vedotin conferred a significant increase in progression-free survival over placebo, with a hazard ratio of 0.57 (P=0.001). The median progression-free survival was 43 months for patients who received brentuximab vedotin and 24 months for those who received placebo.

The most common adverse events (≥20%), of any grade and regardless of causality, in the brentuximab vedotin arm were neutropenia (78%), peripheral sensory neuropathy (56%), thrombocytopenia (41%), anemia (27%), upper respiratory tract infection (26%), fatigue (24%), peripheral motor neuropathy (23%), nausea (22%), cough (21%), and diarrhea (20%).

The most common adverse events (≥20%), of any grade and regardless of causality, in the placebo arm were neutropenia (34%), upper respiratory tract infection (23%), and thrombocytopenia (20%).

In all, 67% of patients on the brentuximab vedotin arm experienced peripheral neuropathy. Of those patients, 85% had resolution (59%) or partial improvement (26%) in symptoms at the time of their last evaluation, with a median time to improvement of 23 weeks (range, 0.1-138).

LUGANO, SWITZERLAND – The immune checkpoint inhibitor avelumab showed efficacy against classical Hodgkin lymphoma among patients with disease progression following allogeneic stem cell transplants (allo-SCT), based on results of a phase 1 trial.

Two of eight patients with disease progression following an allogeneic transplant (allo-SCT) had complete responses (CR) to the programmed death ligand-1 (PD-L1) inhibitor avelumab (Bavencio), three had partial responses (PRs), and two had stable disease, reported Robert Chen, MD, of City of Hope Medical Center in Duarte, California.

“The overall response rate observed in the postallo population of 62.5% suggests that the PD-L1 blockade inhibitor may potentiate a graft-vs.-lymphoma response,” he said at the 14th International Conference on Malignant Lymphoma.

Amplification of the chromosome 9p24.1 locus is frequent in classical Hodgkin lymphoma, and the amplicon contains the genes encoding for PD-L1 and PD-L2, resulting in the over expression of both ligands, Dr. Chen said.

Both nivolumab (Opdivo) and pembrolizumab (Keytruda) are indicated for the treatment of relapsed/refractory classical Hodgkin lymphoma. Both agents block the interactions between PD-1 and both PD-L1 and PD-L2.

“However, it has not been established whether blockade of the PD-1/PD-L1 interaction is necessary and/or sufficient for the therapeutic effect observed in classical Hodgkin lymphoma,” he said.

Avelumab is an anti–PD-L1, immunoglobulin G1 monoclonal antibody that inhibits PD-1/PD-L1 interactions but leaves PD-1/PD-L2 interactions intact. This agent, which recently received FDA approval for the treatment of Merkel cell carcinoma and locally advanced or metastatic urothelial carcinoma, targets tumor cells rather than the T cells targeted by nivolumab and pembrolizumab.

In the phase 1b JAVELIN Hodgkin study, patients with histologically confirmed relapsed/refractory classical Hodgkin lymphoma who were ineligible for transplant or for whom allogeneic or autologous stem cell transplants had failed were enrolled and were assigned to one of five cohorts to receive avelumab in doses ranging from 70 mg intravenously to 10 mg/kg IV every 2 weeks (or every 3 weeks for the 500 mg dose cohort).

A total of 31 patients were randomized in the dose-finding phase of the study. The median patient age was 38 years, 24 patients were younger than 65, and 7 were 65 or older. Only 1 of the 31 patients had received a single prior line of therapy. Of those, 3 had received two prior therapies, 7 had been treated with three prior lines, and 20 had four or more prior lines of therapy. All patients had received brentuximab vedotin (Adcetris).

The median follow-up was 43.3 weeks. In all, nine patients were continuing on avelumab at the time of the data analysis. Because of disease progression, 10 patients discontinued therapy. Additionally, four discontinued because of adverse events, two chose to withdraw, one was removed from the study by the treating physicians, one did not receive treatment, and four others discontinued because of unspecified reasons.

The median treatment duration was 16.9 weeks. The mean number of cycles was 8.6.

The objective response rate was 42%, including five CRs and eight PRs. Three of the CRs were in patients treated at the 70 mg every 2 week dose, and two were in patients treated at the 500 mg every 3 week level.

In all, 23 patients experienced some degree of tumor shrinkage, and 13 had shrinkage greater than 50%.

In an analysis of best overall response among patients whose disease progressed following SCT, the investigators found that two of eight patients (25%) who had disease progression following allo-SCT had a complete response. Three of these patients had a PR, two had stable disease, and one was not eligible for response evaluation.

In contrast, there was only one objective response, a PR, among five patients who had relapses following autologous SCT.

Grade 3 or 4 treatment-related adverse events occurred in 37% of patients. There were no treatment-related deaths. The incidence of treatment-related adverse events was similar across the five dosing cohorts.

“Based on the observed efficacy and safety profiles and unmet need, this study has recently been amended to focus the expansion of patients who progressed post allo-SCT,” Dr. Chen said.

The study was sponsored by Pfizer in collaboration with Merck KGaA, Germany. Dr. Chen has consulted and served in a speakers’ bureau for Seattle Genetics, Millennium, and Genentech. He has also received research funding from Pharmacyclics, Seattle Genetics, Millennium, and Merck.

LUGANO, SWITZERLAND – The immune checkpoint inhibitor avelumab showed efficacy against classical Hodgkin lymphoma among patients with disease progression following allogeneic stem cell transplants (allo-SCT), based on results of a phase 1 trial.

Two of eight patients with disease progression following an allogeneic transplant (allo-SCT) had complete responses (CR) to the programmed death ligand-1 (PD-L1) inhibitor avelumab (Bavencio), three had partial responses (PRs), and two had stable disease, reported Robert Chen, MD, of City of Hope Medical Center in Duarte, California.

“The overall response rate observed in the postallo population of 62.5% suggests that the PD-L1 blockade inhibitor may potentiate a graft-vs.-lymphoma response,” he said at the 14th International Conference on Malignant Lymphoma.

Amplification of the chromosome 9p24.1 locus is frequent in classical Hodgkin lymphoma, and the amplicon contains the genes encoding for PD-L1 and PD-L2, resulting in the over expression of both ligands, Dr. Chen said.

Both nivolumab (Opdivo) and pembrolizumab (Keytruda) are indicated for the treatment of relapsed/refractory classical Hodgkin lymphoma. Both agents block the interactions between PD-1 and both PD-L1 and PD-L2.

“However, it has not been established whether blockade of the PD-1/PD-L1 interaction is necessary and/or sufficient for the therapeutic effect observed in classical Hodgkin lymphoma,” he said.

Avelumab is an anti–PD-L1, immunoglobulin G1 monoclonal antibody that inhibits PD-1/PD-L1 interactions but leaves PD-1/PD-L2 interactions intact. This agent, which recently received FDA approval for the treatment of Merkel cell carcinoma and locally advanced or metastatic urothelial carcinoma, targets tumor cells rather than the T cells targeted by nivolumab and pembrolizumab.

In the phase 1b JAVELIN Hodgkin study, patients with histologically confirmed relapsed/refractory classical Hodgkin lymphoma who were ineligible for transplant or for whom allogeneic or autologous stem cell transplants had failed were enrolled and were assigned to one of five cohorts to receive avelumab in doses ranging from 70 mg intravenously to 10 mg/kg IV every 2 weeks (or every 3 weeks for the 500 mg dose cohort).

A total of 31 patients were randomized in the dose-finding phase of the study. The median patient age was 38 years, 24 patients were younger than 65, and 7 were 65 or older. Only 1 of the 31 patients had received a single prior line of therapy. Of those, 3 had received two prior therapies, 7 had been treated with three prior lines, and 20 had four or more prior lines of therapy. All patients had received brentuximab vedotin (Adcetris).

The median follow-up was 43.3 weeks. In all, nine patients were continuing on avelumab at the time of the data analysis. Because of disease progression, 10 patients discontinued therapy. Additionally, four discontinued because of adverse events, two chose to withdraw, one was removed from the study by the treating physicians, one did not receive treatment, and four others discontinued because of unspecified reasons.

The median treatment duration was 16.9 weeks. The mean number of cycles was 8.6.

The objective response rate was 42%, including five CRs and eight PRs. Three of the CRs were in patients treated at the 70 mg every 2 week dose, and two were in patients treated at the 500 mg every 3 week level.

In all, 23 patients experienced some degree of tumor shrinkage, and 13 had shrinkage greater than 50%.

In an analysis of best overall response among patients whose disease progressed following SCT, the investigators found that two of eight patients (25%) who had disease progression following allo-SCT had a complete response. Three of these patients had a PR, two had stable disease, and one was not eligible for response evaluation.

In contrast, there was only one objective response, a PR, among five patients who had relapses following autologous SCT.

Grade 3 or 4 treatment-related adverse events occurred in 37% of patients. There were no treatment-related deaths. The incidence of treatment-related adverse events was similar across the five dosing cohorts.

“Based on the observed efficacy and safety profiles and unmet need, this study has recently been amended to focus the expansion of patients who progressed post allo-SCT,” Dr. Chen said.

The study was sponsored by Pfizer in collaboration with Merck KGaA, Germany. Dr. Chen has consulted and served in a speakers’ bureau for Seattle Genetics, Millennium, and Genentech. He has also received research funding from Pharmacyclics, Seattle Genetics, Millennium, and Merck.

LUGANO, SWITZERLAND – The immune checkpoint inhibitor avelumab showed efficacy against classical Hodgkin lymphoma among patients with disease progression following allogeneic stem cell transplants (allo-SCT), based on results of a phase 1 trial.

Two of eight patients with disease progression following an allogeneic transplant (allo-SCT) had complete responses (CR) to the programmed death ligand-1 (PD-L1) inhibitor avelumab (Bavencio), three had partial responses (PRs), and two had stable disease, reported Robert Chen, MD, of City of Hope Medical Center in Duarte, California.

“The overall response rate observed in the postallo population of 62.5% suggests that the PD-L1 blockade inhibitor may potentiate a graft-vs.-lymphoma response,” he said at the 14th International Conference on Malignant Lymphoma.

Amplification of the chromosome 9p24.1 locus is frequent in classical Hodgkin lymphoma, and the amplicon contains the genes encoding for PD-L1 and PD-L2, resulting in the over expression of both ligands, Dr. Chen said.

Both nivolumab (Opdivo) and pembrolizumab (Keytruda) are indicated for the treatment of relapsed/refractory classical Hodgkin lymphoma. Both agents block the interactions between PD-1 and both PD-L1 and PD-L2.

“However, it has not been established whether blockade of the PD-1/PD-L1 interaction is necessary and/or sufficient for the therapeutic effect observed in classical Hodgkin lymphoma,” he said.

Avelumab is an anti–PD-L1, immunoglobulin G1 monoclonal antibody that inhibits PD-1/PD-L1 interactions but leaves PD-1/PD-L2 interactions intact. This agent, which recently received FDA approval for the treatment of Merkel cell carcinoma and locally advanced or metastatic urothelial carcinoma, targets tumor cells rather than the T cells targeted by nivolumab and pembrolizumab.

In the phase 1b JAVELIN Hodgkin study, patients with histologically confirmed relapsed/refractory classical Hodgkin lymphoma who were ineligible for transplant or for whom allogeneic or autologous stem cell transplants had failed were enrolled and were assigned to one of five cohorts to receive avelumab in doses ranging from 70 mg intravenously to 10 mg/kg IV every 2 weeks (or every 3 weeks for the 500 mg dose cohort).

A total of 31 patients were randomized in the dose-finding phase of the study. The median patient age was 38 years, 24 patients were younger than 65, and 7 were 65 or older. Only 1 of the 31 patients had received a single prior line of therapy. Of those, 3 had received two prior therapies, 7 had been treated with three prior lines, and 20 had four or more prior lines of therapy. All patients had received brentuximab vedotin (Adcetris).

The median follow-up was 43.3 weeks. In all, nine patients were continuing on avelumab at the time of the data analysis. Because of disease progression, 10 patients discontinued therapy. Additionally, four discontinued because of adverse events, two chose to withdraw, one was removed from the study by the treating physicians, one did not receive treatment, and four others discontinued because of unspecified reasons.

The median treatment duration was 16.9 weeks. The mean number of cycles was 8.6.

The objective response rate was 42%, including five CRs and eight PRs. Three of the CRs were in patients treated at the 70 mg every 2 week dose, and two were in patients treated at the 500 mg every 3 week level.

In all, 23 patients experienced some degree of tumor shrinkage, and 13 had shrinkage greater than 50%.

In an analysis of best overall response among patients whose disease progressed following SCT, the investigators found that two of eight patients (25%) who had disease progression following allo-SCT had a complete response. Three of these patients had a PR, two had stable disease, and one was not eligible for response evaluation.

In contrast, there was only one objective response, a PR, among five patients who had relapses following autologous SCT.

Grade 3 or 4 treatment-related adverse events occurred in 37% of patients. There were no treatment-related deaths. The incidence of treatment-related adverse events was similar across the five dosing cohorts.

“Based on the observed efficacy and safety profiles and unmet need, this study has recently been amended to focus the expansion of patients who progressed post allo-SCT,” Dr. Chen said.

The study was sponsored by Pfizer in collaboration with Merck KGaA, Germany. Dr. Chen has consulted and served in a speakers’ bureau for Seattle Genetics, Millennium, and Genentech. He has also received research funding from Pharmacyclics, Seattle Genetics, Millennium, and Merck.

Micrograph showing HL

LUGANO, SWITZERLAND—Nivolumab can provide long-term treatment for a broad range of adults who have relapsed or refractory classical Hodgkin lymphoma (cHL) after autologous hematopoietic stem cell transplant (auto-HSCT), according to a presentation at the 14th International Conference on Malignant Lymphoma (ICML).

In the phase 2 CheckMate-205 study, cHL patients achieved durable responses regardless of the depth of response, previous exposure to brentuximab vedotin (BV), and refractoriness to prior therapies.

Researchers observed sustained progression-free survival (PFS) in patients with stable disease (SD) or better, and the safety profile of nivolumab was considered acceptable.

“Nivolumab offers a favorable treatment outcome for patients who have relapsed disease after autologous stem cell transplant,” said Michelle Fanale, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Dr Fanale presented results from CheckMate-205 at 14-ICML. The study was sponsored by Bristol-Myers Squibb Company.

CheckMate-205 enrolled 243 adults with relapsed or refractory cHL who had undergone auto-HSCT. Patients were divided into 3 cohorts:

• Cohort A included patients who were naïve to BV (n=63)
• Cohort B included patients who received BV only after auto-HSCT (n=80)
• Cohort C included patients who received BV before and/or after auto-HSCT (n=100).

All patients received nivolumab at 3 mg/kg once every 2 weeks until disease progression or unacceptable toxicity.

In cohort C, patients who were in complete response (CR) for 1 year were to discontinue nivolumab, but they could resume treatment with the drug if they relapsed within 2 years.

Patient characteristics

The median age was 33 (range, 18-65) in cohort A, 37 (range, 18-72) in cohort B, and 32 (range, 19-69) in cohort C.

ECOG performance status was 0 for 62% of patients in cohort A, 53% in cohort B, and 50% in cohort C. The remaining patients had a performance status of 1.

The percentage of patients with stage IV disease was 38% in cohort A, 68% in cohort B, and 61% in cohort C.

The median number of prior therapies was 2 (range, 2-8) in cohort A, 4 (range, 3-15) in cohort B, and 4 (range, 2-9) in cohort C. Fifty-nine percent, 74%, and 69% of patients, respectively, had received prior radiotherapy.

The median time from diagnosis to the first dose of nivolumab was 3.1 years (range, 1.0-30.6) in cohort A, 6.2 years (range, 1.3-25.1) in cohort B, and 3.5 years (range, 1.0-24.9) in cohort C.

The median time from auto-HSCT to the first dose of nivolumab was 1.0 years (range, 0.3-18.2) in cohort A, 3.4 years (range, 0.2-19.0) in cohort B, and 1.7 years (range, 0.2-17.0) in cohort C.

Safety

The most common drug-related adverse events (AEs) were fatigue (23% any grade, 1% grade 3/4), diarrhea (15% any grade, 1% grade 3/4), infusion-related reactions (14% any grade, <1% grade 3/4), rash (12% any grade, 1% grade 3/4), nausea (10% grade 1/2), and pruritus (10% grade 1/2).

The most common drug-related serious AEs were infusion-related reactions (2% any grade, <1% grade 3/4) and pneumonitis (1% grade 1/2).

Drug-related AEs leading to treatment discontinuation were pneumonitis (2% grade 1/2) and autoimmune hepatitis (1% grade 3/4).

There were no deaths due to drug-related AEs.

Response

The objective response rate was 69% overall, 65% in cohort A, 68% in cohort B, and 73% in cohort C.

CR was the best response for 16% of all patients, 29% of cohort A, 13% of cohort B, and 12% of cohort C.

Partial response (PR) was the best response for 53% of all patients, 37% of patients in cohort A, 55% in cohort B, and 61% in cohort C.

SD was the best response for 19% of all patients, 24% of patients in cohort A, 21% in cohort B, and 15% in cohort C.

In post-hoc analyses, responses were similar irrespective of BV treatment sequence.

The median duration of response was 17 months overall, 20 months for cohort A, 16 months for cohort B, and 15 months for cohort C.

The median duration of response in patients with a CR was 20 months overall and for cohorts A and B, but it was 15 months for cohort C.

The median duration of response in patients with a PR was 13 months overall, 17 months for cohort A, 11 months for cohort B, and 13 months for cohort C.

Survival

The median PFS for all patients was 15 months (range, 11-19). The median PFS was 22 months (range, 19-not reached) for patients who achieved a CR, 15 months (range, 11-19) for those who achieved a PR, and 11 months (range, 6-18) for those who had SD.

The median PFS was 18 months (range, 11-22) for patients in cohort A, 15 months (range, 11-20) for cohort B, and 12 months (range, 11-18) for cohort C.

The median overall survival (OS) has not been reached in any of the cohorts. The 12-months OS is 92% overall, 93% in cohort A, 95% in cohort B, and 90% in cohort C.

Patient status after extended follow-up

Forty percent of all patients were still on treatment after extended follow-up, as were 48% of patients in cohort A, 40% in cohort B, and 35% in cohort C.

The most common reason for stopping treatment was disease progression—25% of cohort A, 28% of cohort B, and 24% of cohort C.

Patients also stopped treatment due to nivolumab-related toxicity—5% in cohort A, 11% in cohort B, and 7% in cohort C. Three percent, 1%, and 1%, respectively, stopped due to AEs unrelated to nivolumab.

Three percent of patients in cohort C stopped because they had attained the maximum clinical benefit, and 8% in cohort C completed treatment. This includes 7 patients who discontinued treatment because they were in CR for 1 year.

None of the patients in cohort A or B discontinued because they attained the maximum clinical benefit or because they completed treatment.

Eight percent of patients in cohort A, 10% in cohort B, and 17% in cohort C discontinued so they could proceed to HSCT.

Outcomes after allo-HSCT

Forty-four patients received allogeneic (allo-) HSCT after nivolumab. The median post-HSCT follow-up was 5.5 months (range, 0-19), and the median time from last dose of nivolumab to allo-HSCT was 1.6 months (range, 0.5-13.5).

At 100 days, the rate of grade 2-4 acute graft-vs-host disease (GVHD) was 27%. The rate of grade 3-4 acute GVHD was 17%, and the rate of chronic GVHD was 10%.  At 6 months, the rates were 30%, 20%, and 15%, respectively.

The incidence of transplant-related mortality was 13% at 100 days and at 6 months.

“While there are risks, potentially, for acute GVHD and transplant-related mortality, these aren’t necessarily significantly different from what we’ve seen from other historical publications,” Dr Fanale said.

She cited data showing that the 100-day incidence of acute GVHD in cHL patients who underwent allo-HSCT ranges from 26% to 60%, and the incidence of transplant-related mortality in these patients ranges from 6% to 28%.

Micrograph showing HL

LUGANO, SWITZERLAND—Nivolumab can provide long-term treatment for a broad range of adults who have relapsed or refractory classical Hodgkin lymphoma (cHL) after autologous hematopoietic stem cell transplant (auto-HSCT), according to a presentation at the 14th International Conference on Malignant Lymphoma (ICML).

In the phase 2 CheckMate-205 study, cHL patients achieved durable responses regardless of the depth of response, previous exposure to brentuximab vedotin (BV), and refractoriness to prior therapies.

Researchers observed sustained progression-free survival (PFS) in patients with stable disease (SD) or better, and the safety profile of nivolumab was considered acceptable.

“Nivolumab offers a favorable treatment outcome for patients who have relapsed disease after autologous stem cell transplant,” said Michelle Fanale, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Dr Fanale presented results from CheckMate-205 at 14-ICML. The study was sponsored by Bristol-Myers Squibb Company.

CheckMate-205 enrolled 243 adults with relapsed or refractory cHL who had undergone auto-HSCT. Patients were divided into 3 cohorts:

• Cohort A included patients who were naïve to BV (n=63)
• Cohort B included patients who received BV only after auto-HSCT (n=80)
• Cohort C included patients who received BV before and/or after auto-HSCT (n=100).

All patients received nivolumab at 3 mg/kg once every 2 weeks until disease progression or unacceptable toxicity.

In cohort C, patients who were in complete response (CR) for 1 year were to discontinue nivolumab, but they could resume treatment with the drug if they relapsed within 2 years.

Patient characteristics

The median age was 33 (range, 18-65) in cohort A, 37 (range, 18-72) in cohort B, and 32 (range, 19-69) in cohort C.

ECOG performance status was 0 for 62% of patients in cohort A, 53% in cohort B, and 50% in cohort C. The remaining patients had a performance status of 1.

The percentage of patients with stage IV disease was 38% in cohort A, 68% in cohort B, and 61% in cohort C.

The median number of prior therapies was 2 (range, 2-8) in cohort A, 4 (range, 3-15) in cohort B, and 4 (range, 2-9) in cohort C. Fifty-nine percent, 74%, and 69% of patients, respectively, had received prior radiotherapy.

The median time from diagnosis to the first dose of nivolumab was 3.1 years (range, 1.0-30.6) in cohort A, 6.2 years (range, 1.3-25.1) in cohort B, and 3.5 years (range, 1.0-24.9) in cohort C.

The median time from auto-HSCT to the first dose of nivolumab was 1.0 years (range, 0.3-18.2) in cohort A, 3.4 years (range, 0.2-19.0) in cohort B, and 1.7 years (range, 0.2-17.0) in cohort C.

Safety

The most common drug-related adverse events (AEs) were fatigue (23% any grade, 1% grade 3/4), diarrhea (15% any grade, 1% grade 3/4), infusion-related reactions (14% any grade, <1% grade 3/4), rash (12% any grade, 1% grade 3/4), nausea (10% grade 1/2), and pruritus (10% grade 1/2).

The most common drug-related serious AEs were infusion-related reactions (2% any grade, <1% grade 3/4) and pneumonitis (1% grade 1/2).

Drug-related AEs leading to treatment discontinuation were pneumonitis (2% grade 1/2) and autoimmune hepatitis (1% grade 3/4).

There were no deaths due to drug-related AEs.

Response

The objective response rate was 69% overall, 65% in cohort A, 68% in cohort B, and 73% in cohort C.

CR was the best response for 16% of all patients, 29% of cohort A, 13% of cohort B, and 12% of cohort C.

Partial response (PR) was the best response for 53% of all patients, 37% of patients in cohort A, 55% in cohort B, and 61% in cohort C.

SD was the best response for 19% of all patients, 24% of patients in cohort A, 21% in cohort B, and 15% in cohort C.

In post-hoc analyses, responses were similar irrespective of BV treatment sequence.

The median duration of response was 17 months overall, 20 months for cohort A, 16 months for cohort B, and 15 months for cohort C.

The median duration of response in patients with a CR was 20 months overall and for cohorts A and B, but it was 15 months for cohort C.

The median duration of response in patients with a PR was 13 months overall, 17 months for cohort A, 11 months for cohort B, and 13 months for cohort C.

Survival

The median PFS for all patients was 15 months (range, 11-19). The median PFS was 22 months (range, 19-not reached) for patients who achieved a CR, 15 months (range, 11-19) for those who achieved a PR, and 11 months (range, 6-18) for those who had SD.

The median PFS was 18 months (range, 11-22) for patients in cohort A, 15 months (range, 11-20) for cohort B, and 12 months (range, 11-18) for cohort C.

The median overall survival (OS) has not been reached in any of the cohorts. The 12-months OS is 92% overall, 93% in cohort A, 95% in cohort B, and 90% in cohort C.

Patient status after extended follow-up

Forty percent of all patients were still on treatment after extended follow-up, as were 48% of patients in cohort A, 40% in cohort B, and 35% in cohort C.

The most common reason for stopping treatment was disease progression—25% of cohort A, 28% of cohort B, and 24% of cohort C.

Patients also stopped treatment due to nivolumab-related toxicity—5% in cohort A, 11% in cohort B, and 7% in cohort C. Three percent, 1%, and 1%, respectively, stopped due to AEs unrelated to nivolumab.

Three percent of patients in cohort C stopped because they had attained the maximum clinical benefit, and 8% in cohort C completed treatment. This includes 7 patients who discontinued treatment because they were in CR for 1 year.

None of the patients in cohort A or B discontinued because they attained the maximum clinical benefit or because they completed treatment.

Eight percent of patients in cohort A, 10% in cohort B, and 17% in cohort C discontinued so they could proceed to HSCT.

Outcomes after allo-HSCT

Forty-four patients received allogeneic (allo-) HSCT after nivolumab. The median post-HSCT follow-up was 5.5 months (range, 0-19), and the median time from last dose of nivolumab to allo-HSCT was 1.6 months (range, 0.5-13.5).

At 100 days, the rate of grade 2-4 acute graft-vs-host disease (GVHD) was 27%. The rate of grade 3-4 acute GVHD was 17%, and the rate of chronic GVHD was 10%.  At 6 months, the rates were 30%, 20%, and 15%, respectively.

The incidence of transplant-related mortality was 13% at 100 days and at 6 months.

“While there are risks, potentially, for acute GVHD and transplant-related mortality, these aren’t necessarily significantly different from what we’ve seen from other historical publications,” Dr Fanale said.

She cited data showing that the 100-day incidence of acute GVHD in cHL patients who underwent allo-HSCT ranges from 26% to 60%, and the incidence of transplant-related mortality in these patients ranges from 6% to 28%.

Micrograph showing HL

LUGANO, SWITZERLAND—Nivolumab can provide long-term treatment for a broad range of adults who have relapsed or refractory classical Hodgkin lymphoma (cHL) after autologous hematopoietic stem cell transplant (auto-HSCT), according to a presentation at the 14th International Conference on Malignant Lymphoma (ICML).

In the phase 2 CheckMate-205 study, cHL patients achieved durable responses regardless of the depth of response, previous exposure to brentuximab vedotin (BV), and refractoriness to prior therapies.

Researchers observed sustained progression-free survival (PFS) in patients with stable disease (SD) or better, and the safety profile of nivolumab was considered acceptable.

“Nivolumab offers a favorable treatment outcome for patients who have relapsed disease after autologous stem cell transplant,” said Michelle Fanale, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Dr Fanale presented results from CheckMate-205 at 14-ICML. The study was sponsored by Bristol-Myers Squibb Company.

CheckMate-205 enrolled 243 adults with relapsed or refractory cHL who had undergone auto-HSCT. Patients were divided into 3 cohorts:

• Cohort A included patients who were naïve to BV (n=63)
• Cohort B included patients who received BV only after auto-HSCT (n=80)
• Cohort C included patients who received BV before and/or after auto-HSCT (n=100).

All patients received nivolumab at 3 mg/kg once every 2 weeks until disease progression or unacceptable toxicity.

In cohort C, patients who were in complete response (CR) for 1 year were to discontinue nivolumab, but they could resume treatment with the drug if they relapsed within 2 years.

Patient characteristics

The median age was 33 (range, 18-65) in cohort A, 37 (range, 18-72) in cohort B, and 32 (range, 19-69) in cohort C.

ECOG performance status was 0 for 62% of patients in cohort A, 53% in cohort B, and 50% in cohort C. The remaining patients had a performance status of 1.

The percentage of patients with stage IV disease was 38% in cohort A, 68% in cohort B, and 61% in cohort C.

The median number of prior therapies was 2 (range, 2-8) in cohort A, 4 (range, 3-15) in cohort B, and 4 (range, 2-9) in cohort C. Fifty-nine percent, 74%, and 69% of patients, respectively, had received prior radiotherapy.

The median time from diagnosis to the first dose of nivolumab was 3.1 years (range, 1.0-30.6) in cohort A, 6.2 years (range, 1.3-25.1) in cohort B, and 3.5 years (range, 1.0-24.9) in cohort C.

The median time from auto-HSCT to the first dose of nivolumab was 1.0 years (range, 0.3-18.2) in cohort A, 3.4 years (range, 0.2-19.0) in cohort B, and 1.7 years (range, 0.2-17.0) in cohort C.

Safety

The most common drug-related adverse events (AEs) were fatigue (23% any grade, 1% grade 3/4), diarrhea (15% any grade, 1% grade 3/4), infusion-related reactions (14% any grade, <1% grade 3/4), rash (12% any grade, 1% grade 3/4), nausea (10% grade 1/2), and pruritus (10% grade 1/2).

The most common drug-related serious AEs were infusion-related reactions (2% any grade, <1% grade 3/4) and pneumonitis (1% grade 1/2).

Drug-related AEs leading to treatment discontinuation were pneumonitis (2% grade 1/2) and autoimmune hepatitis (1% grade 3/4).

There were no deaths due to drug-related AEs.

Response

The objective response rate was 69% overall, 65% in cohort A, 68% in cohort B, and 73% in cohort C.

CR was the best response for 16% of all patients, 29% of cohort A, 13% of cohort B, and 12% of cohort C.

Partial response (PR) was the best response for 53% of all patients, 37% of patients in cohort A, 55% in cohort B, and 61% in cohort C.

SD was the best response for 19% of all patients, 24% of patients in cohort A, 21% in cohort B, and 15% in cohort C.

In post-hoc analyses, responses were similar irrespective of BV treatment sequence.

The median duration of response was 17 months overall, 20 months for cohort A, 16 months for cohort B, and 15 months for cohort C.

The median duration of response in patients with a CR was 20 months overall and for cohorts A and B, but it was 15 months for cohort C.

The median duration of response in patients with a PR was 13 months overall, 17 months for cohort A, 11 months for cohort B, and 13 months for cohort C.

Survival

The median PFS for all patients was 15 months (range, 11-19). The median PFS was 22 months (range, 19-not reached) for patients who achieved a CR, 15 months (range, 11-19) for those who achieved a PR, and 11 months (range, 6-18) for those who had SD.

The median PFS was 18 months (range, 11-22) for patients in cohort A, 15 months (range, 11-20) for cohort B, and 12 months (range, 11-18) for cohort C.

The median overall survival (OS) has not been reached in any of the cohorts. The 12-months OS is 92% overall, 93% in cohort A, 95% in cohort B, and 90% in cohort C.

Patient status after extended follow-up

Forty percent of all patients were still on treatment after extended follow-up, as were 48% of patients in cohort A, 40% in cohort B, and 35% in cohort C.

The most common reason for stopping treatment was disease progression—25% of cohort A, 28% of cohort B, and 24% of cohort C.

Patients also stopped treatment due to nivolumab-related toxicity—5% in cohort A, 11% in cohort B, and 7% in cohort C. Three percent, 1%, and 1%, respectively, stopped due to AEs unrelated to nivolumab.

Three percent of patients in cohort C stopped because they had attained the maximum clinical benefit, and 8% in cohort C completed treatment. This includes 7 patients who discontinued treatment because they were in CR for 1 year.

None of the patients in cohort A or B discontinued because they attained the maximum clinical benefit or because they completed treatment.

Eight percent of patients in cohort A, 10% in cohort B, and 17% in cohort C discontinued so they could proceed to HSCT.

Outcomes after allo-HSCT

Forty-four patients received allogeneic (allo-) HSCT after nivolumab. The median post-HSCT follow-up was 5.5 months (range, 0-19), and the median time from last dose of nivolumab to allo-HSCT was 1.6 months (range, 0.5-13.5).

At 100 days, the rate of grade 2-4 acute graft-vs-host disease (GVHD) was 27%. The rate of grade 3-4 acute GVHD was 17%, and the rate of chronic GVHD was 10%.  At 6 months, the rates were 30%, 20%, and 15%, respectively.

The incidence of transplant-related mortality was 13% at 100 days and at 6 months.

“While there are risks, potentially, for acute GVHD and transplant-related mortality, these aren’t necessarily significantly different from what we’ve seen from other historical publications,” Dr Fanale said.

She cited data showing that the 100-day incidence of acute GVHD in cHL patients who underwent allo-HSCT ranges from 26% to 60%, and the incidence of transplant-related mortality in these patients ranges from 6% to 28%.