Hematology Times

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The U.S. Food and Drug Administration (FDA) has approved emapalumab-lzsg (Gamifant®) to treat primary hemophagocytic lymphohistiocytosis (HLH).

Emapalumab, an interferon gamma-blocking antibody, is approved to treat to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy.

Emapalumab is the first treatment to be FDA-approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019.

The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation.

The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).

The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy.

Patients received emapalumab in combination with dexamethasone.

At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n=7), partial response (n=8), or HLH improvement (n=2).

Seventy percent (n=19) of patients went on to hematopoietic stem cell transplant.

The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).

Additional results from this study can be found in the prescribing information for emapalumab, which is available at www.gamifant.com.

Results are also scheduled to be presented at the 2018 ASH Annual Meeting (abstract LBA-6).

Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.

Photo from Business Wire

The U.S. Food and Drug Administration (FDA) has approved emapalumab-lzsg (Gamifant®) to treat primary hemophagocytic lymphohistiocytosis (HLH).

Emapalumab, an interferon gamma-blocking antibody, is approved to treat to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy.

Emapalumab is the first treatment to be FDA-approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019.

The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation.

The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).

The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy.

Patients received emapalumab in combination with dexamethasone.

At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n=7), partial response (n=8), or HLH improvement (n=2).

Seventy percent (n=19) of patients went on to hematopoietic stem cell transplant.

The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).

Additional results from this study can be found in the prescribing information for emapalumab, which is available at www.gamifant.com.

Results are also scheduled to be presented at the 2018 ASH Annual Meeting (abstract LBA-6).

Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.

Photo from Business Wire

The U.S. Food and Drug Administration (FDA) has approved emapalumab-lzsg (Gamifant®) to treat primary hemophagocytic lymphohistiocytosis (HLH).

Emapalumab, an interferon gamma-blocking antibody, is approved to treat to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy.

Emapalumab is the first treatment to be FDA-approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019.

The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation.

The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).

The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy.

Patients received emapalumab in combination with dexamethasone.

At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n=7), partial response (n=8), or HLH improvement (n=2).

Seventy percent (n=19) of patients went on to hematopoietic stem cell transplant.

The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).

Additional results from this study can be found in the prescribing information for emapalumab, which is available at www.gamifant.com.

Results are also scheduled to be presented at the 2018 ASH Annual Meeting (abstract LBA-6).

Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.

Photo courtesy of the CDC

Phase 2 results suggest a three-drug regimen may improve response rates in patients with proteasome inhibitor (PI)-refractory multiple myeloma (MM).

The combination—nelfinavir, bortezomib, and dexamethasone (NeVd)—produced an objective response rate (ORR) of 65% in this trial.

In comparison, past studies have shown response rates of 24% to 36% in the PI-refractory MM population.^1,2,3

“The unprecedented ORR of NeVd observed in this heavily pretreated, multi-refractory setting warrants further investigation to explore the potential of nelfinavir in combination with PIs . . . ,” Christoph Driessen, of Kantonsspital St. Gallen in Switzerland, and his colleagues wrote in a letter to Blood.

The researchers noted that NeVd previously demonstrated activity in a phase 1 trial of MM patients who were refractory to both bortezomib and lenalidomide.

For the phase 2 study (NCT02188537), Dr. Driessen and his colleagues tested NeVd in MM patients who were refractory to their most recent PI-containing regimen and were previously exposed to or intolerant of at least one immunomodulatory drug.

The 34 patients had a median age of 67 (range, 42-82). Sixty-two percent were male, 38% had poor-risk cytogenetics, and most had a performance status of 0 (59%) or 1 (32%).

All patients had received lenalidomide, 47% had prior pomalidomide, 76% had prior high-dose chemotherapy, and 76% had a prior transplant.

All patients were bortezomib-refractory, 79% were refractory to a PI and lenalidomide, 44% were refractory to a PI and pomalidomide, and 38% were refractory to a PI, lenalidomide, and pomalidomide.

In this study, the patients received:

• Nelfinavir at 2500 mg on days 1 to 14 twice daily
• Bortezomib at 1.3 mg/m² subcutaneously on days 1, 4, 8, and 11
• Dexamethasone at 20 mg orally on days 1 to 2, 4 to 5, 8 to 9, and 11 to 12.

The patients were treated for up to six 21-day cycles. They received a median of 4.5 cycles (range, 1-6).

Results

The ORR was 65%, with 17 partial responses (PRs) and five very good PRs. Three patients had a minimal response, and four had stable disease.

The ORR (PR or better) was:

• 77% in patients with poor-risk cytogenetics
• 67% in patients with fewer than five prior therapies
• 63% in patients with five or more prior therapies
• 70% in patients refractory to bortezomib and lenalidomide
• 60% in patients refractory to bortezomib and pomalidomide
• 62% in patients refractory to bortezomib, lenalidomide, and pomalidomide.

The researchers said the clinical benefit of NeVd may have been underestimated in this trial because patients were only able to receive six cycles of treatment on study due to a lack of external funding support.

“The time course of paraprotein levels also suggests that individual patients might potentially have experienced myeloma control if NeVd had been continued until progression,” the researchers wrote.

Five patients did receive more than six cycles of NeVd on a compassionate-use basis. In all, 27 patients received additional anti-myeloma treatment during follow-up.

The median progression-free survival was 12 weeks for the entire cohort and 16 weeks among patients who achieved a PR or better.

The median overall survival was 12 months, and 17 patients had died as of November 2016.

The researchers said the most common adverse events in this trial were anemia (97%), thrombocytopenia (82%), hypertension (53%), diarrhea (47%), fatigue (38%), and dyspnea (35%).

There were four deaths during treatment—three due to septicemia and one from heart failure. Three of the deaths were associated with underlying pneumonia.

“Although this mortality rate is consistent with the background mortality among patients with heavily pretreated, refractory myeloma, these findings suggest that prophylactic antibiotic therapy should be considered in those with low neutrophil counts and/or advanced age undergoing NeVd treatment,” the researchers wrote.

This work was supported by the Swiss Group for Clinical Cancer Research, the Swiss State Secretariat for Education, Research and Innovation, the Rising Tide Foundation for Clinical Cancer Research, and the Gateway for Cancer Research.

Most of the researchers declared no competing financial interests, but one reported personal fees from Celgene, Takeda, Amgen, Novartis, and Janssen-Cilag that were unrelated to this trial.

1. Lokhorst HM et al. N Engl J Med. 2015; 373(13):1207-1219.

2. Dimopoulos MA et al. Blood. 2016;128(4): 497-503.

3. Siegel DS et al. Blood. 2012;120(14):2817-2825.

Photo courtesy of the CDC

Phase 2 results suggest a three-drug regimen may improve response rates in patients with proteasome inhibitor (PI)-refractory multiple myeloma (MM).

The combination—nelfinavir, bortezomib, and dexamethasone (NeVd)—produced an objective response rate (ORR) of 65% in this trial.

In comparison, past studies have shown response rates of 24% to 36% in the PI-refractory MM population.^1,2,3

“The unprecedented ORR of NeVd observed in this heavily pretreated, multi-refractory setting warrants further investigation to explore the potential of nelfinavir in combination with PIs . . . ,” Christoph Driessen, of Kantonsspital St. Gallen in Switzerland, and his colleagues wrote in a letter to Blood.

The researchers noted that NeVd previously demonstrated activity in a phase 1 trial of MM patients who were refractory to both bortezomib and lenalidomide.

For the phase 2 study (NCT02188537), Dr. Driessen and his colleagues tested NeVd in MM patients who were refractory to their most recent PI-containing regimen and were previously exposed to or intolerant of at least one immunomodulatory drug.

The 34 patients had a median age of 67 (range, 42-82). Sixty-two percent were male, 38% had poor-risk cytogenetics, and most had a performance status of 0 (59%) or 1 (32%).

All patients had received lenalidomide, 47% had prior pomalidomide, 76% had prior high-dose chemotherapy, and 76% had a prior transplant.

All patients were bortezomib-refractory, 79% were refractory to a PI and lenalidomide, 44% were refractory to a PI and pomalidomide, and 38% were refractory to a PI, lenalidomide, and pomalidomide.

In this study, the patients received:

• Nelfinavir at 2500 mg on days 1 to 14 twice daily
• Bortezomib at 1.3 mg/m² subcutaneously on days 1, 4, 8, and 11
• Dexamethasone at 20 mg orally on days 1 to 2, 4 to 5, 8 to 9, and 11 to 12.

The patients were treated for up to six 21-day cycles. They received a median of 4.5 cycles (range, 1-6).

Results

The ORR was 65%, with 17 partial responses (PRs) and five very good PRs. Three patients had a minimal response, and four had stable disease.

The ORR (PR or better) was:

• 77% in patients with poor-risk cytogenetics
• 67% in patients with fewer than five prior therapies
• 63% in patients with five or more prior therapies
• 70% in patients refractory to bortezomib and lenalidomide
• 60% in patients refractory to bortezomib and pomalidomide
• 62% in patients refractory to bortezomib, lenalidomide, and pomalidomide.

The researchers said the clinical benefit of NeVd may have been underestimated in this trial because patients were only able to receive six cycles of treatment on study due to a lack of external funding support.

“The time course of paraprotein levels also suggests that individual patients might potentially have experienced myeloma control if NeVd had been continued until progression,” the researchers wrote.

Five patients did receive more than six cycles of NeVd on a compassionate-use basis. In all, 27 patients received additional anti-myeloma treatment during follow-up.

The median progression-free survival was 12 weeks for the entire cohort and 16 weeks among patients who achieved a PR or better.

The median overall survival was 12 months, and 17 patients had died as of November 2016.

The researchers said the most common adverse events in this trial were anemia (97%), thrombocytopenia (82%), hypertension (53%), diarrhea (47%), fatigue (38%), and dyspnea (35%).

There were four deaths during treatment—three due to septicemia and one from heart failure. Three of the deaths were associated with underlying pneumonia.

“Although this mortality rate is consistent with the background mortality among patients with heavily pretreated, refractory myeloma, these findings suggest that prophylactic antibiotic therapy should be considered in those with low neutrophil counts and/or advanced age undergoing NeVd treatment,” the researchers wrote.

This work was supported by the Swiss Group for Clinical Cancer Research, the Swiss State Secretariat for Education, Research and Innovation, the Rising Tide Foundation for Clinical Cancer Research, and the Gateway for Cancer Research.

Most of the researchers declared no competing financial interests, but one reported personal fees from Celgene, Takeda, Amgen, Novartis, and Janssen-Cilag that were unrelated to this trial.

1. Lokhorst HM et al. N Engl J Med. 2015; 373(13):1207-1219.

2. Dimopoulos MA et al. Blood. 2016;128(4): 497-503.

3. Siegel DS et al. Blood. 2012;120(14):2817-2825.

Photo courtesy of the CDC

Phase 2 results suggest a three-drug regimen may improve response rates in patients with proteasome inhibitor (PI)-refractory multiple myeloma (MM).

The combination—nelfinavir, bortezomib, and dexamethasone (NeVd)—produced an objective response rate (ORR) of 65% in this trial.

In comparison, past studies have shown response rates of 24% to 36% in the PI-refractory MM population.^1,2,3

“The unprecedented ORR of NeVd observed in this heavily pretreated, multi-refractory setting warrants further investigation to explore the potential of nelfinavir in combination with PIs . . . ,” Christoph Driessen, of Kantonsspital St. Gallen in Switzerland, and his colleagues wrote in a letter to Blood.

The researchers noted that NeVd previously demonstrated activity in a phase 1 trial of MM patients who were refractory to both bortezomib and lenalidomide.

For the phase 2 study (NCT02188537), Dr. Driessen and his colleagues tested NeVd in MM patients who were refractory to their most recent PI-containing regimen and were previously exposed to or intolerant of at least one immunomodulatory drug.

The 34 patients had a median age of 67 (range, 42-82). Sixty-two percent were male, 38% had poor-risk cytogenetics, and most had a performance status of 0 (59%) or 1 (32%).

All patients had received lenalidomide, 47% had prior pomalidomide, 76% had prior high-dose chemotherapy, and 76% had a prior transplant.

All patients were bortezomib-refractory, 79% were refractory to a PI and lenalidomide, 44% were refractory to a PI and pomalidomide, and 38% were refractory to a PI, lenalidomide, and pomalidomide.

In this study, the patients received:

• Nelfinavir at 2500 mg on days 1 to 14 twice daily
• Bortezomib at 1.3 mg/m² subcutaneously on days 1, 4, 8, and 11
• Dexamethasone at 20 mg orally on days 1 to 2, 4 to 5, 8 to 9, and 11 to 12.

The patients were treated for up to six 21-day cycles. They received a median of 4.5 cycles (range, 1-6).

Results

The ORR was 65%, with 17 partial responses (PRs) and five very good PRs. Three patients had a minimal response, and four had stable disease.

The ORR (PR or better) was:

• 77% in patients with poor-risk cytogenetics
• 67% in patients with fewer than five prior therapies
• 63% in patients with five or more prior therapies
• 70% in patients refractory to bortezomib and lenalidomide
• 60% in patients refractory to bortezomib and pomalidomide
• 62% in patients refractory to bortezomib, lenalidomide, and pomalidomide.

The researchers said the clinical benefit of NeVd may have been underestimated in this trial because patients were only able to receive six cycles of treatment on study due to a lack of external funding support.

“The time course of paraprotein levels also suggests that individual patients might potentially have experienced myeloma control if NeVd had been continued until progression,” the researchers wrote.

Five patients did receive more than six cycles of NeVd on a compassionate-use basis. In all, 27 patients received additional anti-myeloma treatment during follow-up.

The median progression-free survival was 12 weeks for the entire cohort and 16 weeks among patients who achieved a PR or better.

The median overall survival was 12 months, and 17 patients had died as of November 2016.

The researchers said the most common adverse events in this trial were anemia (97%), thrombocytopenia (82%), hypertension (53%), diarrhea (47%), fatigue (38%), and dyspnea (35%).

There were four deaths during treatment—three due to septicemia and one from heart failure. Three of the deaths were associated with underlying pneumonia.

“Although this mortality rate is consistent with the background mortality among patients with heavily pretreated, refractory myeloma, these findings suggest that prophylactic antibiotic therapy should be considered in those with low neutrophil counts and/or advanced age undergoing NeVd treatment,” the researchers wrote.

This work was supported by the Swiss Group for Clinical Cancer Research, the Swiss State Secretariat for Education, Research and Innovation, the Rising Tide Foundation for Clinical Cancer Research, and the Gateway for Cancer Research.

Most of the researchers declared no competing financial interests, but one reported personal fees from Celgene, Takeda, Amgen, Novartis, and Janssen-Cilag that were unrelated to this trial.

1. Lokhorst HM et al. N Engl J Med. 2015; 373(13):1207-1219.

2. Dimopoulos MA et al. Blood. 2016;128(4): 497-503.

3. Siegel DS et al. Blood. 2012;120(14):2817-2825.

Photo by Chad McNeeley

A retrospective study suggests elderly patients with non-Hodgkin lymphoma (NHL) are more likely to die, but not relapse, within a year of allogeneic hematopoietic stem cell transplant (allo-HSCT).

The rate of non-relapse mortality (NRM) at 1 year was significantly higher for elderly patients than for middle-aged or young patients.

However, the 3-year rate of relapse was similar across the age groups.

Charalampia Kyriakou, MD, PhD, of University College London in the U.K., and her colleagues reported these findings in Biology of Blood and Marrow Transplantation.

The investigators analyzed 3,919 patients with NHL who underwent allo-HSCT between 2003 and 2013.

The patients had follicular lymphoma (n=1,461), diffuse large B-cell lymphoma (n=1,192), mantle cell lymphoma (n=823), and peripheral T-cell lymphoma (n=443).

At the time of transplant, about 85% of patients were chemo-sensitive, with the remainder being chemo-refractory.

Results

The investigators compared outcomes in patients assigned to three age groups—young (18-50), middle-aged (51-65), and elderly (66-77).

NRM at 1 year was 13% for young patients, 20% for middle-aged patients, and 33% for elderly patients (P<0.001).

Overall survival at 3 years was 60% in young patients, 54% in middle-aged patients, and 38% in the elderly (P<0.001).

In contrast to these significant associations between age and survival, the rate of relapse at 3 years remained relatively consistent—30% in young patients, 31% in middle-aged patients, and 28% in elderly patients (P=0.355).

The increased risk of NRM in elderly patients could not be fully explained by comorbidities, although these were more common in the elderly.

After analyzing information from a subset of patients, the investigators concluded that “the presence of comorbidities is a significant risk factor for NRM and survival, but this does not fully explain the outcome disadvantages in our [elderly] group.”

Therefore, age remains an independent risk factor.

The investigators did not report conflicts of interest.

Photo by Chad McNeeley

A retrospective study suggests elderly patients with non-Hodgkin lymphoma (NHL) are more likely to die, but not relapse, within a year of allogeneic hematopoietic stem cell transplant (allo-HSCT).

The rate of non-relapse mortality (NRM) at 1 year was significantly higher for elderly patients than for middle-aged or young patients.

However, the 3-year rate of relapse was similar across the age groups.

Charalampia Kyriakou, MD, PhD, of University College London in the U.K., and her colleagues reported these findings in Biology of Blood and Marrow Transplantation.

The investigators analyzed 3,919 patients with NHL who underwent allo-HSCT between 2003 and 2013.

The patients had follicular lymphoma (n=1,461), diffuse large B-cell lymphoma (n=1,192), mantle cell lymphoma (n=823), and peripheral T-cell lymphoma (n=443).

At the time of transplant, about 85% of patients were chemo-sensitive, with the remainder being chemo-refractory.

Results

The investigators compared outcomes in patients assigned to three age groups—young (18-50), middle-aged (51-65), and elderly (66-77).

NRM at 1 year was 13% for young patients, 20% for middle-aged patients, and 33% for elderly patients (P<0.001).

Overall survival at 3 years was 60% in young patients, 54% in middle-aged patients, and 38% in the elderly (P<0.001).

In contrast to these significant associations between age and survival, the rate of relapse at 3 years remained relatively consistent—30% in young patients, 31% in middle-aged patients, and 28% in elderly patients (P=0.355).

The increased risk of NRM in elderly patients could not be fully explained by comorbidities, although these were more common in the elderly.

After analyzing information from a subset of patients, the investigators concluded that “the presence of comorbidities is a significant risk factor for NRM and survival, but this does not fully explain the outcome disadvantages in our [elderly] group.”

Therefore, age remains an independent risk factor.

The investigators did not report conflicts of interest.

Photo by Chad McNeeley

A retrospective study suggests elderly patients with non-Hodgkin lymphoma (NHL) are more likely to die, but not relapse, within a year of allogeneic hematopoietic stem cell transplant (allo-HSCT).

The rate of non-relapse mortality (NRM) at 1 year was significantly higher for elderly patients than for middle-aged or young patients.

However, the 3-year rate of relapse was similar across the age groups.

Charalampia Kyriakou, MD, PhD, of University College London in the U.K., and her colleagues reported these findings in Biology of Blood and Marrow Transplantation.

The investigators analyzed 3,919 patients with NHL who underwent allo-HSCT between 2003 and 2013.

The patients had follicular lymphoma (n=1,461), diffuse large B-cell lymphoma (n=1,192), mantle cell lymphoma (n=823), and peripheral T-cell lymphoma (n=443).

At the time of transplant, about 85% of patients were chemo-sensitive, with the remainder being chemo-refractory.

Results

The investigators compared outcomes in patients assigned to three age groups—young (18-50), middle-aged (51-65), and elderly (66-77).

NRM at 1 year was 13% for young patients, 20% for middle-aged patients, and 33% for elderly patients (P<0.001).

Overall survival at 3 years was 60% in young patients, 54% in middle-aged patients, and 38% in the elderly (P<0.001).

In contrast to these significant associations between age and survival, the rate of relapse at 3 years remained relatively consistent—30% in young patients, 31% in middle-aged patients, and 28% in elderly patients (P=0.355).

The increased risk of NRM in elderly patients could not be fully explained by comorbidities, although these were more common in the elderly.

After analyzing information from a subset of patients, the investigators concluded that “the presence of comorbidities is a significant risk factor for NRM and survival, but this does not fully explain the outcome disadvantages in our [elderly] group.”

Therefore, age remains an independent risk factor.

The investigators did not report conflicts of interest.

Photo by Junior Libby

A recent survey suggests Americans are nearly as worried about the cost of a cancer diagnosis as they are about dying from cancer.

The cost of cancer care was a top concern even among people who had no prior experience with cancer.

At the same time, cancer patients/survivors admitted to delaying or forgoing care due to costs, and caregivers reported taking “dramatic” actions to pay for their loved one’s care.

These are findings from the American Society of Clinical Oncology (ASCO)’s second annual National Cancer Opinion Survey.

The survey was conducted online by The Harris Poll from July 10, 2018, to August 10, 2018. It included 4,887 U.S. adults age 18 and older—1,001 of whom have or had cancer.

Cost among top concerns

Death and pain/suffering were the top concerns related to a cancer diagnosis. Fifty-four percent of respondents said death would be one of their greatest concerns if they were diagnosed with cancer, and the same percentage rated pain/suffering a top concern.

Forty-four percent of respondents said paying for cancer treatment would be a top concern, and 45% said the same about the financial impact of a cancer diagnosis on their family. When combined, financial issues were a top concern for 57% of respondents.

Paying for treatment was a top concern for:

• 36% of respondents who had/have cancer
• 51% of caregivers
• 43% of people with no prior cancer experience.

The financial impact on family was a top concern for:

• 39% of respondents who had/have cancer
• 55% of caregivers
• 42% of people with no prior cancer experience.

Cutting costs

Sixty-one percent of caregivers surveyed said they or another relative have taken a “dramatic” step to help pay for their loved one’s care, including:

• Dipping into savings accounts (35%)
• Working extra hours (23%)
• Taking an early withdrawal from a retirement account or college fund (14%)
• Postponing retirement (14%)
• Taking out a second mortgage or other type of loan (13%)
• Taking an additional job (13%)
• Selling family heirlooms (9%).

Twenty percent of cancer patients/survivors said they have taken actions to reduce treatment costs, including:

• Delaying scans (7%)
• Skipping or delaying appointments (7%)
• Skipping doses of prescribed treatment (6%)
• Postponing or not filling prescriptions (5%)
• Refusing treatment (3%).

“Patients are right to be concerned about the financial impact of a cancer diagnosis on their families,” said Richard L. Schilsky, MD, ASCO’s chief medical officer.

“It’s clear that high treatment costs are taking a serious toll not only on patients, but also on the people who care for them. If a family member has been diagnosed with cancer, the sole focus should be helping them get well. Instead, Americans are worrying about affording treatment, and, in many cases, they’re making serious personal sacrifices to help pay for their loved ones’ care.”

Photo by Junior Libby

A recent survey suggests Americans are nearly as worried about the cost of a cancer diagnosis as they are about dying from cancer.

The cost of cancer care was a top concern even among people who had no prior experience with cancer.

At the same time, cancer patients/survivors admitted to delaying or forgoing care due to costs, and caregivers reported taking “dramatic” actions to pay for their loved one’s care.

These are findings from the American Society of Clinical Oncology (ASCO)’s second annual National Cancer Opinion Survey.

The survey was conducted online by The Harris Poll from July 10, 2018, to August 10, 2018. It included 4,887 U.S. adults age 18 and older—1,001 of whom have or had cancer.

Cost among top concerns

Death and pain/suffering were the top concerns related to a cancer diagnosis. Fifty-four percent of respondents said death would be one of their greatest concerns if they were diagnosed with cancer, and the same percentage rated pain/suffering a top concern.

Forty-four percent of respondents said paying for cancer treatment would be a top concern, and 45% said the same about the financial impact of a cancer diagnosis on their family. When combined, financial issues were a top concern for 57% of respondents.

Paying for treatment was a top concern for:

• 36% of respondents who had/have cancer
• 51% of caregivers
• 43% of people with no prior cancer experience.

The financial impact on family was a top concern for:

• 39% of respondents who had/have cancer
• 55% of caregivers
• 42% of people with no prior cancer experience.

Cutting costs

Sixty-one percent of caregivers surveyed said they or another relative have taken a “dramatic” step to help pay for their loved one’s care, including:

• Dipping into savings accounts (35%)
• Working extra hours (23%)
• Taking an early withdrawal from a retirement account or college fund (14%)
• Postponing retirement (14%)
• Taking out a second mortgage or other type of loan (13%)
• Taking an additional job (13%)
• Selling family heirlooms (9%).

Twenty percent of cancer patients/survivors said they have taken actions to reduce treatment costs, including:

• Delaying scans (7%)
• Skipping or delaying appointments (7%)
• Skipping doses of prescribed treatment (6%)
• Postponing or not filling prescriptions (5%)
• Refusing treatment (3%).

“Patients are right to be concerned about the financial impact of a cancer diagnosis on their families,” said Richard L. Schilsky, MD, ASCO’s chief medical officer.

“It’s clear that high treatment costs are taking a serious toll not only on patients, but also on the people who care for them. If a family member has been diagnosed with cancer, the sole focus should be helping them get well. Instead, Americans are worrying about affording treatment, and, in many cases, they’re making serious personal sacrifices to help pay for their loved ones’ care.”

Photo by Junior Libby

A recent survey suggests Americans are nearly as worried about the cost of a cancer diagnosis as they are about dying from cancer.

The cost of cancer care was a top concern even among people who had no prior experience with cancer.

At the same time, cancer patients/survivors admitted to delaying or forgoing care due to costs, and caregivers reported taking “dramatic” actions to pay for their loved one’s care.

These are findings from the American Society of Clinical Oncology (ASCO)’s second annual National Cancer Opinion Survey.

The survey was conducted online by The Harris Poll from July 10, 2018, to August 10, 2018. It included 4,887 U.S. adults age 18 and older—1,001 of whom have or had cancer.

Cost among top concerns

Death and pain/suffering were the top concerns related to a cancer diagnosis. Fifty-four percent of respondents said death would be one of their greatest concerns if they were diagnosed with cancer, and the same percentage rated pain/suffering a top concern.

Forty-four percent of respondents said paying for cancer treatment would be a top concern, and 45% said the same about the financial impact of a cancer diagnosis on their family. When combined, financial issues were a top concern for 57% of respondents.

Paying for treatment was a top concern for:

• 36% of respondents who had/have cancer
• 51% of caregivers
• 43% of people with no prior cancer experience.

The financial impact on family was a top concern for:

• 39% of respondents who had/have cancer
• 55% of caregivers
• 42% of people with no prior cancer experience.

Cutting costs

Sixty-one percent of caregivers surveyed said they or another relative have taken a “dramatic” step to help pay for their loved one’s care, including:

• Dipping into savings accounts (35%)
• Working extra hours (23%)
• Taking an early withdrawal from a retirement account or college fund (14%)
• Postponing retirement (14%)
• Taking out a second mortgage or other type of loan (13%)
• Taking an additional job (13%)
• Selling family heirlooms (9%).

Twenty percent of cancer patients/survivors said they have taken actions to reduce treatment costs, including:

• Delaying scans (7%)
• Skipping or delaying appointments (7%)
• Skipping doses of prescribed treatment (6%)
• Postponing or not filling prescriptions (5%)
• Refusing treatment (3%).

“Patients are right to be concerned about the financial impact of a cancer diagnosis on their families,” said Richard L. Schilsky, MD, ASCO’s chief medical officer.

“It’s clear that high treatment costs are taking a serious toll not only on patients, but also on the people who care for them. If a family member has been diagnosed with cancer, the sole focus should be helping them get well. Instead, Americans are worrying about affording treatment, and, in many cases, they’re making serious personal sacrifices to help pay for their loved ones’ care.”

and David Joseph Russell

Bortezomib may help overcome treatment resistance in patients with Waldenström’s macroglobulinemia (WM) and CXCR4 mutations, according to a new study.

Researchers assessed the impact of treatment with bortezomib and rituximab in patients with WM, based on their CXCR4 mutation status.

The team found no significant difference in progression-free survival or overall survival between patients with CXCR4 mutations and those with wild-type CXCR4.

Romanos Sklavenitis-Pistofidis, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues reported this discovery in Blood.

The researchers’ main analysis included 43 patients with WM, 17 (39.5%) of whom had a CXCR4 mutation.

All patients who carried a CXCR4 mutation also had MYD88 L265P. Ten patients had frameshift mutations, one patient had a nonsense mutation, and six patients had missense mutations.

The patients were treated with bortezomib and rituximab, either upfront (n=14) or in the relapsed/refractory (n=29) setting, as part of a phase 2 trial.

Bortezomib was given at 1.6 mg/m² on days 1, 8, and 15 every 28 days for six cycles, and rituximab was given at 375 mg/m² on days 1, 8, 15, and 22 during cycles one and four. Patients were taken off therapy after two cycles if they had progressive disease.

The median follow-up was 90.7 months.

The researchers found no significant difference between CXCR4-mutated and wild-type patients when it came to progression-free survival (P=0.994) or overall survival (P=0.407).

The researchers repeated their analysis after excluding six patients with missense mutations and accounting for different treatment settings and found that survival remained unchanged.

“We report, for the first time, that a bortezomib-based combination is impervious to the impact of CXCR4 mutations in a cohort of patients with WM,” the researchers wrote.

“Previously, we had shown this to be true in WM cell lines, whereby genetically engineering BCWM.1 and MWCL-1 to overexpress CXCR4 had no impact on bortezomib resistance.”

The researchers noted, however, that the mechanism at work here may be different than what is seen with bortezomib in other cancers.

“Different experiments have linked CXCR4 expression and bortezomib in a variety of ways in other hematological malignancies, including multiple myeloma,” the researchers wrote.

“However, despite the complicated association in those cancer types, in WM, there seems to be a consistently neutral effect of CXCR4 mutations on bortezomib resistance in both cell line and patient data.”

The researchers recommended that this theory be tested in a prospective trial of bortezomib-based therapy in WM patients with CXCR4 mutations.

Another thing to be determined, they said, is the role of rituximab in the survival results seen in the current analysis.

This study was supported by the National Institutes of Health, the Leukemia and Lymphoma Society, and the International Waldenström Macroglobulinemia Foundation. One of the authors reported consulting and research funding from Takeda, which markets bortezomib, and other companies.

and David Joseph Russell

Bortezomib may help overcome treatment resistance in patients with Waldenström’s macroglobulinemia (WM) and CXCR4 mutations, according to a new study.

Researchers assessed the impact of treatment with bortezomib and rituximab in patients with WM, based on their CXCR4 mutation status.

The team found no significant difference in progression-free survival or overall survival between patients with CXCR4 mutations and those with wild-type CXCR4.

Romanos Sklavenitis-Pistofidis, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues reported this discovery in Blood.

The researchers’ main analysis included 43 patients with WM, 17 (39.5%) of whom had a CXCR4 mutation.

All patients who carried a CXCR4 mutation also had MYD88 L265P. Ten patients had frameshift mutations, one patient had a nonsense mutation, and six patients had missense mutations.

The patients were treated with bortezomib and rituximab, either upfront (n=14) or in the relapsed/refractory (n=29) setting, as part of a phase 2 trial.

Bortezomib was given at 1.6 mg/m² on days 1, 8, and 15 every 28 days for six cycles, and rituximab was given at 375 mg/m² on days 1, 8, 15, and 22 during cycles one and four. Patients were taken off therapy after two cycles if they had progressive disease.

The median follow-up was 90.7 months.

The researchers found no significant difference between CXCR4-mutated and wild-type patients when it came to progression-free survival (P=0.994) or overall survival (P=0.407).

The researchers repeated their analysis after excluding six patients with missense mutations and accounting for different treatment settings and found that survival remained unchanged.

“We report, for the first time, that a bortezomib-based combination is impervious to the impact of CXCR4 mutations in a cohort of patients with WM,” the researchers wrote.

“Previously, we had shown this to be true in WM cell lines, whereby genetically engineering BCWM.1 and MWCL-1 to overexpress CXCR4 had no impact on bortezomib resistance.”

The researchers noted, however, that the mechanism at work here may be different than what is seen with bortezomib in other cancers.

“Different experiments have linked CXCR4 expression and bortezomib in a variety of ways in other hematological malignancies, including multiple myeloma,” the researchers wrote.

“However, despite the complicated association in those cancer types, in WM, there seems to be a consistently neutral effect of CXCR4 mutations on bortezomib resistance in both cell line and patient data.”

The researchers recommended that this theory be tested in a prospective trial of bortezomib-based therapy in WM patients with CXCR4 mutations.

Another thing to be determined, they said, is the role of rituximab in the survival results seen in the current analysis.

This study was supported by the National Institutes of Health, the Leukemia and Lymphoma Society, and the International Waldenström Macroglobulinemia Foundation. One of the authors reported consulting and research funding from Takeda, which markets bortezomib, and other companies.

and David Joseph Russell

Bortezomib may help overcome treatment resistance in patients with Waldenström’s macroglobulinemia (WM) and CXCR4 mutations, according to a new study.

Researchers assessed the impact of treatment with bortezomib and rituximab in patients with WM, based on their CXCR4 mutation status.

The team found no significant difference in progression-free survival or overall survival between patients with CXCR4 mutations and those with wild-type CXCR4.

Romanos Sklavenitis-Pistofidis, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues reported this discovery in Blood.

The researchers’ main analysis included 43 patients with WM, 17 (39.5%) of whom had a CXCR4 mutation.

All patients who carried a CXCR4 mutation also had MYD88 L265P. Ten patients had frameshift mutations, one patient had a nonsense mutation, and six patients had missense mutations.

The patients were treated with bortezomib and rituximab, either upfront (n=14) or in the relapsed/refractory (n=29) setting, as part of a phase 2 trial.

Bortezomib was given at 1.6 mg/m² on days 1, 8, and 15 every 28 days for six cycles, and rituximab was given at 375 mg/m² on days 1, 8, 15, and 22 during cycles one and four. Patients were taken off therapy after two cycles if they had progressive disease.

The median follow-up was 90.7 months.

The researchers found no significant difference between CXCR4-mutated and wild-type patients when it came to progression-free survival (P=0.994) or overall survival (P=0.407).

The researchers repeated their analysis after excluding six patients with missense mutations and accounting for different treatment settings and found that survival remained unchanged.

“We report, for the first time, that a bortezomib-based combination is impervious to the impact of CXCR4 mutations in a cohort of patients with WM,” the researchers wrote.

“Previously, we had shown this to be true in WM cell lines, whereby genetically engineering BCWM.1 and MWCL-1 to overexpress CXCR4 had no impact on bortezomib resistance.”

The researchers noted, however, that the mechanism at work here may be different than what is seen with bortezomib in other cancers.

“Different experiments have linked CXCR4 expression and bortezomib in a variety of ways in other hematological malignancies, including multiple myeloma,” the researchers wrote.

“However, despite the complicated association in those cancer types, in WM, there seems to be a consistently neutral effect of CXCR4 mutations on bortezomib resistance in both cell line and patient data.”

The researchers recommended that this theory be tested in a prospective trial of bortezomib-based therapy in WM patients with CXCR4 mutations.

Another thing to be determined, they said, is the role of rituximab in the survival results seen in the current analysis.

This study was supported by the National Institutes of Health, the Leukemia and Lymphoma Society, and the International Waldenström Macroglobulinemia Foundation. One of the authors reported consulting and research funding from Takeda, which markets bortezomib, and other companies.

Photo courtesy of Amgen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding marketing authorization for blinatumomab (Blincyto) to include treatment of minimal residual disease (MRD).

The CHMP has recommended approval for blinatumomab as monotherapy for adults with Philadelphia chromosome-negative, CD19-positive, B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in first or second complete remission with MRD greater than or equal to 0.1%.

The CHMP had originally adopted a negative opinion on extending the use of blinatumomab to these patients. However, the committee re-examined its opinion and reversed that decision.

The CHMP has requested that Amgen, the company developing blinatumomab, provide results from ongoing studies to support the new approval.

The CHMP’s recommendations are reviewed by the European Commission (EC), which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The EC usually makes a decision within 67 days of CHMP recommendations.

Blinatumomab is already EC-approved as monotherapy for:

• Adults with Philadelphia chromosome-negative, CD19-positive, relapsed or refractory BCP-ALL.
• Pediatric patients age 1 year or older who have relapsed/refractory, Philadelphia chromosome-negative, CD19-positive BCP-ALL and have received at least two prior therapies or relapsed after allogeneic hematopoietic stem cell transplant.

CHMP’s reversal of opinion

In July, the CHMP recommended against approving blinatumomab to treat patients with MRD based on data from the BLAST trial. Results from this phase 2 trial were published in Blood in April.

The CHMP noted that, although blinatumomab produced MRD negativity in many patients in the BLAST trial, there is no strong evidence that this leads to improved survival.

Given the uncertainty, the CHMP was of the opinion that the benefits of blinatumomab do not outweigh its risks in MRD-positive BCP-ALL patients.

However, Amgen request a re-examination of the CHMP’s opinion, and the CHMP complied.

During the re-examination, the CHMP reviewed all the data and consulted a group of experts.

The experts concluded, and the CHMP agreed, that, although there is no strong evidence of improved survival, the available data indicate a good response to blinatumomab, with around 78% of patients becoming MRD-negative after treatment.

The CHMP also noted that MRD-positive patients have a high risk of relapse and few treatment options.

Therefore, the committee concluded that the benefits of blinatumomab outweigh its risks in this patient population.

The CHMP recommended granting the change to the marketing authorization but also requested that Amgen provide data from ongoing studies of blinatumomab in MRD-positive patients, once those data are available.

Photo courtesy of Amgen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding marketing authorization for blinatumomab (Blincyto) to include treatment of minimal residual disease (MRD).

The CHMP has recommended approval for blinatumomab as monotherapy for adults with Philadelphia chromosome-negative, CD19-positive, B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in first or second complete remission with MRD greater than or equal to 0.1%.

The CHMP had originally adopted a negative opinion on extending the use of blinatumomab to these patients. However, the committee re-examined its opinion and reversed that decision.

The CHMP has requested that Amgen, the company developing blinatumomab, provide results from ongoing studies to support the new approval.

The CHMP’s recommendations are reviewed by the European Commission (EC), which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The EC usually makes a decision within 67 days of CHMP recommendations.

Blinatumomab is already EC-approved as monotherapy for:

• Adults with Philadelphia chromosome-negative, CD19-positive, relapsed or refractory BCP-ALL.
• Pediatric patients age 1 year or older who have relapsed/refractory, Philadelphia chromosome-negative, CD19-positive BCP-ALL and have received at least two prior therapies or relapsed after allogeneic hematopoietic stem cell transplant.

CHMP’s reversal of opinion

In July, the CHMP recommended against approving blinatumomab to treat patients with MRD based on data from the BLAST trial. Results from this phase 2 trial were published in Blood in April.

The CHMP noted that, although blinatumomab produced MRD negativity in many patients in the BLAST trial, there is no strong evidence that this leads to improved survival.

Given the uncertainty, the CHMP was of the opinion that the benefits of blinatumomab do not outweigh its risks in MRD-positive BCP-ALL patients.

However, Amgen request a re-examination of the CHMP’s opinion, and the CHMP complied.

During the re-examination, the CHMP reviewed all the data and consulted a group of experts.

The experts concluded, and the CHMP agreed, that, although there is no strong evidence of improved survival, the available data indicate a good response to blinatumomab, with around 78% of patients becoming MRD-negative after treatment.

The CHMP also noted that MRD-positive patients have a high risk of relapse and few treatment options.

Therefore, the committee concluded that the benefits of blinatumomab outweigh its risks in this patient population.

The CHMP recommended granting the change to the marketing authorization but also requested that Amgen provide data from ongoing studies of blinatumomab in MRD-positive patients, once those data are available.

Photo courtesy of Amgen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding marketing authorization for blinatumomab (Blincyto) to include treatment of minimal residual disease (MRD).

The CHMP has recommended approval for blinatumomab as monotherapy for adults with Philadelphia chromosome-negative, CD19-positive, B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in first or second complete remission with MRD greater than or equal to 0.1%.

The CHMP had originally adopted a negative opinion on extending the use of blinatumomab to these patients. However, the committee re-examined its opinion and reversed that decision.

The CHMP has requested that Amgen, the company developing blinatumomab, provide results from ongoing studies to support the new approval.

The CHMP’s recommendations are reviewed by the European Commission (EC), which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.

The EC usually makes a decision within 67 days of CHMP recommendations.

Blinatumomab is already EC-approved as monotherapy for:

• Adults with Philadelphia chromosome-negative, CD19-positive, relapsed or refractory BCP-ALL.
• Pediatric patients age 1 year or older who have relapsed/refractory, Philadelphia chromosome-negative, CD19-positive BCP-ALL and have received at least two prior therapies or relapsed after allogeneic hematopoietic stem cell transplant.

CHMP’s reversal of opinion

In July, the CHMP recommended against approving blinatumomab to treat patients with MRD based on data from the BLAST trial. Results from this phase 2 trial were published in Blood in April.

The CHMP noted that, although blinatumomab produced MRD negativity in many patients in the BLAST trial, there is no strong evidence that this leads to improved survival.

Given the uncertainty, the CHMP was of the opinion that the benefits of blinatumomab do not outweigh its risks in MRD-positive BCP-ALL patients.

However, Amgen request a re-examination of the CHMP’s opinion, and the CHMP complied.

During the re-examination, the CHMP reviewed all the data and consulted a group of experts.

The experts concluded, and the CHMP agreed, that, although there is no strong evidence of improved survival, the available data indicate a good response to blinatumomab, with around 78% of patients becoming MRD-negative after treatment.

The CHMP also noted that MRD-positive patients have a high risk of relapse and few treatment options.

Therefore, the committee concluded that the benefits of blinatumomab outweigh its risks in this patient population.

The CHMP recommended granting the change to the marketing authorization but also requested that Amgen provide data from ongoing studies of blinatumomab in MRD-positive patients, once those data are available.

Photo courtesy of GSK

The U.S. Food and Drug Administration (FDA) has expanded the approved use of eltrombopag (Promacta®) in severe aplastic anemia (SAA).

Eltrombopag is now approved for use in combination with standard immunosuppressive therapy as first-line treatment for adults and pediatric patients age 2 and older with SAA.

Eltrombopag received breakthrough therapy designation and priority review for this indication.

Eltrombopag is also FDA-approved for SAA patients who have had an insufficient response to immunosuppressive therapy, for patients with chronic immune thrombocytopenia who have had an insufficient response to other treatments, and to treat thrombocytopenia in patients with chronic hepatitis C virus infection.

The FDA’s latest approval of eltrombopag is based on results from a phase 1/2 trial (NCT01623167), which were published in The New England Journal of Medicine in April 2017.

Updated results from the trial are available in the prescribing information for eltrombopag.

The trial included 153 previously untreated SAA patients age 2 and older. The patients received eltrombopag in combination with horse antithymocyte globulin and cyclosporine.

The starting dose of eltrombopag was:

• 150 mg once daily for patients age 12 and older (75 mg for East and Southeast Asians)
• 75 mg once daily for patients ages 6 to 11 (37.5 mg for East and Southeast Asians)
• 5 mg/kg once daily for patients ages 2 to 5 (1.25 mg/kg for East and Southeast Asians).

Patients were divided into three cohorts with different dosing schedules.

The recommended schedule, from the third cohort (n=92), was eltrombopag from day 1 to month 6, plus horse antithymocyte globulin and cyclosporine. All patients in this cohort were eligible to receive a low dose of cyclosporine for an additional 18 months if they achieved a hematologic response at 6 months.

Among the patients treated at the recommended dosing schedule, the 6-month overall response rate was 79%, and the complete response rate was 44%.

The median duration of both overall and complete response was 24.3 months.

The most common adverse events in these patients were ALT increase (29%), AST increase (17%), blood bilirubin increase (17%), rash (8%), and skin discoloration including hyperpigmentation (5%).

Eltrombopag is a product of Novartis.

Photo courtesy of GSK

The U.S. Food and Drug Administration (FDA) has expanded the approved use of eltrombopag (Promacta®) in severe aplastic anemia (SAA).

Eltrombopag is now approved for use in combination with standard immunosuppressive therapy as first-line treatment for adults and pediatric patients age 2 and older with SAA.

Eltrombopag received breakthrough therapy designation and priority review for this indication.

Eltrombopag is also FDA-approved for SAA patients who have had an insufficient response to immunosuppressive therapy, for patients with chronic immune thrombocytopenia who have had an insufficient response to other treatments, and to treat thrombocytopenia in patients with chronic hepatitis C virus infection.

The FDA’s latest approval of eltrombopag is based on results from a phase 1/2 trial (NCT01623167), which were published in The New England Journal of Medicine in April 2017.

Updated results from the trial are available in the prescribing information for eltrombopag.

The trial included 153 previously untreated SAA patients age 2 and older. The patients received eltrombopag in combination with horse antithymocyte globulin and cyclosporine.

The starting dose of eltrombopag was:

• 150 mg once daily for patients age 12 and older (75 mg for East and Southeast Asians)
• 75 mg once daily for patients ages 6 to 11 (37.5 mg for East and Southeast Asians)
• 5 mg/kg once daily for patients ages 2 to 5 (1.25 mg/kg for East and Southeast Asians).

Patients were divided into three cohorts with different dosing schedules.

The recommended schedule, from the third cohort (n=92), was eltrombopag from day 1 to month 6, plus horse antithymocyte globulin and cyclosporine. All patients in this cohort were eligible to receive a low dose of cyclosporine for an additional 18 months if they achieved a hematologic response at 6 months.

Among the patients treated at the recommended dosing schedule, the 6-month overall response rate was 79%, and the complete response rate was 44%.

The median duration of both overall and complete response was 24.3 months.

The most common adverse events in these patients were ALT increase (29%), AST increase (17%), blood bilirubin increase (17%), rash (8%), and skin discoloration including hyperpigmentation (5%).

Eltrombopag is a product of Novartis.

Photo courtesy of GSK

The U.S. Food and Drug Administration (FDA) has expanded the approved use of eltrombopag (Promacta®) in severe aplastic anemia (SAA).

Eltrombopag is now approved for use in combination with standard immunosuppressive therapy as first-line treatment for adults and pediatric patients age 2 and older with SAA.

Eltrombopag received breakthrough therapy designation and priority review for this indication.

Eltrombopag is also FDA-approved for SAA patients who have had an insufficient response to immunosuppressive therapy, for patients with chronic immune thrombocytopenia who have had an insufficient response to other treatments, and to treat thrombocytopenia in patients with chronic hepatitis C virus infection.

The FDA’s latest approval of eltrombopag is based on results from a phase 1/2 trial (NCT01623167), which were published in The New England Journal of Medicine in April 2017.

Updated results from the trial are available in the prescribing information for eltrombopag.

The trial included 153 previously untreated SAA patients age 2 and older. The patients received eltrombopag in combination with horse antithymocyte globulin and cyclosporine.

The starting dose of eltrombopag was:

• 150 mg once daily for patients age 12 and older (75 mg for East and Southeast Asians)
• 75 mg once daily for patients ages 6 to 11 (37.5 mg for East and Southeast Asians)
• 5 mg/kg once daily for patients ages 2 to 5 (1.25 mg/kg for East and Southeast Asians).

Patients were divided into three cohorts with different dosing schedules.

The recommended schedule, from the third cohort (n=92), was eltrombopag from day 1 to month 6, plus horse antithymocyte globulin and cyclosporine. All patients in this cohort were eligible to receive a low dose of cyclosporine for an additional 18 months if they achieved a hematologic response at 6 months.

Among the patients treated at the recommended dosing schedule, the 6-month overall response rate was 79%, and the complete response rate was 44%.

The median duration of both overall and complete response was 24.3 months.

The most common adverse events in these patients were ALT increase (29%), AST increase (17%), blood bilirubin increase (17%), rash (8%), and skin discoloration including hyperpigmentation (5%).

Eltrombopag is a product of Novartis.

Photo from Business Wire

The U.S. Food and Drug Administration (FDA) has approved a new indication for brentuximab vedotin (ADCETRIS®) less than 2 weeks after receiving the completed supplemental biologics license application (sBLA).

Brentuximab vedotin is now approved for use in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) to treat adults with previously untreated systemic anaplastic large-cell lymphoma or other CD30-expressing peripheral T-cell lymphomas (PTCLs), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.

The FDA granted priority review and breakthrough therapy designation to the sBLA for brentuximab vedotin in this indication.

The FDA reviewed the sBLA under the Real-Time Oncology Review Pilot Program, which led to approval less than 2 weeks after the application was submitted in full.

“The Real-Time Oncology Review program allows the FDA to access key data prior to the official submission of the application, allowing the review team to begin their review earlier and communicate with the sponsor prior to the application’s actual submission,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products.

“When the sponsor submits the completed application, the review team will already be familiar with the data and be able to conduct a more efficient, timely, and thorough review.”

Trial data

The FDA’s approval is based on results from the phase 3 ECHELON-2 trial (NCT01777152).

Seattle Genetics, Inc. and Takeda Pharmaceutical Company Limited announced results from this trial last month. Additional results are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 997).

The trial enrolled 452 patients with CD30-positive PTCL. The patients were randomized to receive brentuximab vedotin (BV) plus CHP or cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).

The objective response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.003). The complete response rate was 68% and 56%, respectively (P=0.007).

Progression-free survival was significantly better in the BV-CHP arm than in the CHOP arm (hazard ratio=0.71; P=0.011), as was overall survival (hazard ratio=0.66; P=0.024).

The most common adverse events of any grade that occurred in at least 20% of patients in the BV-CHP arm were peripheral neuropathy, nausea, diarrhea, neutropenia, lymphopenia, fatigue, mucositis, constipation, alopecia, pyrexia, vomiting, and anemia.

Serious adverse events occurring in at least 2% of patients in the BV-CHP arm included febrile neutropenia, pneumonia, pyrexia, and sepsis.

Results of this trial suggest prophylactic growth factors should be given to previously untreated PTCL patients receiving BV-CHP (starting at cycle 1).

Photo from Business Wire

The U.S. Food and Drug Administration (FDA) has approved a new indication for brentuximab vedotin (ADCETRIS®) less than 2 weeks after receiving the completed supplemental biologics license application (sBLA).

Brentuximab vedotin is now approved for use in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) to treat adults with previously untreated systemic anaplastic large-cell lymphoma or other CD30-expressing peripheral T-cell lymphomas (PTCLs), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.

The FDA granted priority review and breakthrough therapy designation to the sBLA for brentuximab vedotin in this indication.

The FDA reviewed the sBLA under the Real-Time Oncology Review Pilot Program, which led to approval less than 2 weeks after the application was submitted in full.

“The Real-Time Oncology Review program allows the FDA to access key data prior to the official submission of the application, allowing the review team to begin their review earlier and communicate with the sponsor prior to the application’s actual submission,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products.

“When the sponsor submits the completed application, the review team will already be familiar with the data and be able to conduct a more efficient, timely, and thorough review.”

Trial data

The FDA’s approval is based on results from the phase 3 ECHELON-2 trial (NCT01777152).

Seattle Genetics, Inc. and Takeda Pharmaceutical Company Limited announced results from this trial last month. Additional results are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 997).

The trial enrolled 452 patients with CD30-positive PTCL. The patients were randomized to receive brentuximab vedotin (BV) plus CHP or cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).

The objective response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.003). The complete response rate was 68% and 56%, respectively (P=0.007).

Progression-free survival was significantly better in the BV-CHP arm than in the CHOP arm (hazard ratio=0.71; P=0.011), as was overall survival (hazard ratio=0.66; P=0.024).

The most common adverse events of any grade that occurred in at least 20% of patients in the BV-CHP arm were peripheral neuropathy, nausea, diarrhea, neutropenia, lymphopenia, fatigue, mucositis, constipation, alopecia, pyrexia, vomiting, and anemia.

Serious adverse events occurring in at least 2% of patients in the BV-CHP arm included febrile neutropenia, pneumonia, pyrexia, and sepsis.

Results of this trial suggest prophylactic growth factors should be given to previously untreated PTCL patients receiving BV-CHP (starting at cycle 1).

Photo from Business Wire

The U.S. Food and Drug Administration (FDA) has approved a new indication for brentuximab vedotin (ADCETRIS®) less than 2 weeks after receiving the completed supplemental biologics license application (sBLA).

Brentuximab vedotin is now approved for use in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) to treat adults with previously untreated systemic anaplastic large-cell lymphoma or other CD30-expressing peripheral T-cell lymphomas (PTCLs), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.

The FDA granted priority review and breakthrough therapy designation to the sBLA for brentuximab vedotin in this indication.

The FDA reviewed the sBLA under the Real-Time Oncology Review Pilot Program, which led to approval less than 2 weeks after the application was submitted in full.

“The Real-Time Oncology Review program allows the FDA to access key data prior to the official submission of the application, allowing the review team to begin their review earlier and communicate with the sponsor prior to the application’s actual submission,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products.

“When the sponsor submits the completed application, the review team will already be familiar with the data and be able to conduct a more efficient, timely, and thorough review.”

Trial data

The FDA’s approval is based on results from the phase 3 ECHELON-2 trial (NCT01777152).

Seattle Genetics, Inc. and Takeda Pharmaceutical Company Limited announced results from this trial last month. Additional results are scheduled to be presented at the 2018 ASH Annual Meeting (abstract 997).

The trial enrolled 452 patients with CD30-positive PTCL. The patients were randomized to receive brentuximab vedotin (BV) plus CHP or cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).

The objective response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.003). The complete response rate was 68% and 56%, respectively (P=0.007).

Progression-free survival was significantly better in the BV-CHP arm than in the CHOP arm (hazard ratio=0.71; P=0.011), as was overall survival (hazard ratio=0.66; P=0.024).

The most common adverse events of any grade that occurred in at least 20% of patients in the BV-CHP arm were peripheral neuropathy, nausea, diarrhea, neutropenia, lymphopenia, fatigue, mucositis, constipation, alopecia, pyrexia, vomiting, and anemia.

Serious adverse events occurring in at least 2% of patients in the BV-CHP arm included febrile neutropenia, pneumonia, pyrexia, and sepsis.

Results of this trial suggest prophylactic growth factors should be given to previously untreated PTCL patients receiving BV-CHP (starting at cycle 1).

Johns Hopkins Medicine

Education can improve adherence to venous thromboembolism (VTE) prophylaxis among hospitalized patients, according to researchers.

They assessed data from more than 19,000 hospital stays and found that “real-time” educational interventions directed toward patients and nurses significantly reduced nonadministration of prescribed VTE prophylaxis.

However, this did not translate to a significant reduction in VTE incidence.

Elliott Haut, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues reported these results in JAMA Network Open.

For this study, the researchers evaluated patients who were prescribed VTE prophylaxis while admitted to Johns Hopkins Hospital between April 1, 2015, and December 31, 2015.

The researchers evaluated patients in 16 hospital units. Four units were targeted for educational intervention, and the remaining 12 units served as controls.

The educational interventions were given only when patients did not receive prescribed VTE prophylaxis. A bedside nurse would document nonadministration, and an alert built into the hospital’s electronic medical record would email and page a health educator.

If the patient had refused prophylaxis, the patient would receive an educational bundle on VTE, which could consist of any or all of the following (patient’s choice):

• A one-on-one discussion with the health educator
• A two-page paper handout (available in eight languages)
• A 10-minute educational video (on a tablet).

If the nonadministration of prophylaxis was not due to patient refusal or contraindication, the health educator would educate the bedside nurse about the importance of giving all prescribed doses of VTE prophylaxis.

The study included 19,652 patient visits during which VTE prophylaxis was prescribed.

Of these, 726 visits were targeted for educational intervention. In 272 visits, the intervention was administered to a nurse alone (n=45) or the nurse and the patient (n=227).

For the remaining 454 visits, the patient was discharged before the intervention (n=123), there was an order to discontinue prophylaxis (n=111), there was a technical error (n=55), the patient (n=43) or health educator (n=41) was off unit, or “other” reasons (n=81).

Results

The proportion of nonadministered doses of VTE prophylaxis declined significantly in the hospital units targeted with educational intervention—from 9.1% pre-intervention to 5.6% post-intervention (odds ratio [OR]=0.57, P<0.001).

However, there was no significant change in the control units—13.6% and 13.3%, respectively (OR=0.98, P=0.62).

The proportion of nonadministered doses for reasons other than patient refusal decreased significantly in the intervention units—from 2.3% to 1.7% (OR, 0.74, P=0.01)—but not in control units—from 3.4% to 3.3% (OR=0.98, P=0.69).

The proportion of nonadministered doses due to patient refusal decreased significantly in the intervention units—from 5.9% to 3.4% (OR=0.53, P<0.001)—but not in control units—from 8.7% to 8.5% (OR=0.98, P=0.71).

“Our study demonstrates that educating patients quickly, as soon as we learn about a missed dose, is not only possible to implement at a large hospital but is effective in ensuring that patients take the drugs that can save their lives,” Dr. Haut said.

“The educational bundles we created are effective and optimize busy clinicians’ already packed schedules,” added study author Brandyn Lau, of the Johns Hopkins University School of Medicine.

“At the end of the day, we’re here to deliver high quality care and keep patients safe, and this is one method of achieving that mission.”

However, the improved adherence to VTE prophylaxis did not translate to a significant reduction in VTE in this study.

The incidence of VTE decreased from 0.30% to 0.18% (OR=0.60) in intervention units and from 0.24% to 0.20% in control units (OR=0.81).

For all patients, the incidence of VTE was 0.26% pre-intervention and 0.19% post-intervention (P=0.46).

This research was supported by a contract from the Patient-Centered Outcomes Research Institute. The study authors reported support from various government agencies and private organizations.

Johns Hopkins Medicine

Education can improve adherence to venous thromboembolism (VTE) prophylaxis among hospitalized patients, according to researchers.

They assessed data from more than 19,000 hospital stays and found that “real-time” educational interventions directed toward patients and nurses significantly reduced nonadministration of prescribed VTE prophylaxis.

However, this did not translate to a significant reduction in VTE incidence.

Elliott Haut, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues reported these results in JAMA Network Open.

For this study, the researchers evaluated patients who were prescribed VTE prophylaxis while admitted to Johns Hopkins Hospital between April 1, 2015, and December 31, 2015.

The researchers evaluated patients in 16 hospital units. Four units were targeted for educational intervention, and the remaining 12 units served as controls.

The educational interventions were given only when patients did not receive prescribed VTE prophylaxis. A bedside nurse would document nonadministration, and an alert built into the hospital’s electronic medical record would email and page a health educator.

If the patient had refused prophylaxis, the patient would receive an educational bundle on VTE, which could consist of any or all of the following (patient’s choice):

• A one-on-one discussion with the health educator
• A two-page paper handout (available in eight languages)
• A 10-minute educational video (on a tablet).

If the nonadministration of prophylaxis was not due to patient refusal or contraindication, the health educator would educate the bedside nurse about the importance of giving all prescribed doses of VTE prophylaxis.

The study included 19,652 patient visits during which VTE prophylaxis was prescribed.

Of these, 726 visits were targeted for educational intervention. In 272 visits, the intervention was administered to a nurse alone (n=45) or the nurse and the patient (n=227).

For the remaining 454 visits, the patient was discharged before the intervention (n=123), there was an order to discontinue prophylaxis (n=111), there was a technical error (n=55), the patient (n=43) or health educator (n=41) was off unit, or “other” reasons (n=81).

Results

The proportion of nonadministered doses of VTE prophylaxis declined significantly in the hospital units targeted with educational intervention—from 9.1% pre-intervention to 5.6% post-intervention (odds ratio [OR]=0.57, P<0.001).

However, there was no significant change in the control units—13.6% and 13.3%, respectively (OR=0.98, P=0.62).

The proportion of nonadministered doses for reasons other than patient refusal decreased significantly in the intervention units—from 2.3% to 1.7% (OR, 0.74, P=0.01)—but not in control units—from 3.4% to 3.3% (OR=0.98, P=0.69).

The proportion of nonadministered doses due to patient refusal decreased significantly in the intervention units—from 5.9% to 3.4% (OR=0.53, P<0.001)—but not in control units—from 8.7% to 8.5% (OR=0.98, P=0.71).

“Our study demonstrates that educating patients quickly, as soon as we learn about a missed dose, is not only possible to implement at a large hospital but is effective in ensuring that patients take the drugs that can save their lives,” Dr. Haut said.

“The educational bundles we created are effective and optimize busy clinicians’ already packed schedules,” added study author Brandyn Lau, of the Johns Hopkins University School of Medicine.

“At the end of the day, we’re here to deliver high quality care and keep patients safe, and this is one method of achieving that mission.”

However, the improved adherence to VTE prophylaxis did not translate to a significant reduction in VTE in this study.

The incidence of VTE decreased from 0.30% to 0.18% (OR=0.60) in intervention units and from 0.24% to 0.20% in control units (OR=0.81).

For all patients, the incidence of VTE was 0.26% pre-intervention and 0.19% post-intervention (P=0.46).

This research was supported by a contract from the Patient-Centered Outcomes Research Institute. The study authors reported support from various government agencies and private organizations.

Johns Hopkins Medicine

Education can improve adherence to venous thromboembolism (VTE) prophylaxis among hospitalized patients, according to researchers.

They assessed data from more than 19,000 hospital stays and found that “real-time” educational interventions directed toward patients and nurses significantly reduced nonadministration of prescribed VTE prophylaxis.

However, this did not translate to a significant reduction in VTE incidence.

Elliott Haut, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues reported these results in JAMA Network Open.

For this study, the researchers evaluated patients who were prescribed VTE prophylaxis while admitted to Johns Hopkins Hospital between April 1, 2015, and December 31, 2015.

The researchers evaluated patients in 16 hospital units. Four units were targeted for educational intervention, and the remaining 12 units served as controls.

The educational interventions were given only when patients did not receive prescribed VTE prophylaxis. A bedside nurse would document nonadministration, and an alert built into the hospital’s electronic medical record would email and page a health educator.

If the patient had refused prophylaxis, the patient would receive an educational bundle on VTE, which could consist of any or all of the following (patient’s choice):

• A one-on-one discussion with the health educator
• A two-page paper handout (available in eight languages)
• A 10-minute educational video (on a tablet).

If the nonadministration of prophylaxis was not due to patient refusal or contraindication, the health educator would educate the bedside nurse about the importance of giving all prescribed doses of VTE prophylaxis.

The study included 19,652 patient visits during which VTE prophylaxis was prescribed.

Of these, 726 visits were targeted for educational intervention. In 272 visits, the intervention was administered to a nurse alone (n=45) or the nurse and the patient (n=227).

For the remaining 454 visits, the patient was discharged before the intervention (n=123), there was an order to discontinue prophylaxis (n=111), there was a technical error (n=55), the patient (n=43) or health educator (n=41) was off unit, or “other” reasons (n=81).

Results

The proportion of nonadministered doses of VTE prophylaxis declined significantly in the hospital units targeted with educational intervention—from 9.1% pre-intervention to 5.6% post-intervention (odds ratio [OR]=0.57, P<0.001).

However, there was no significant change in the control units—13.6% and 13.3%, respectively (OR=0.98, P=0.62).

The proportion of nonadministered doses for reasons other than patient refusal decreased significantly in the intervention units—from 2.3% to 1.7% (OR, 0.74, P=0.01)—but not in control units—from 3.4% to 3.3% (OR=0.98, P=0.69).

The proportion of nonadministered doses due to patient refusal decreased significantly in the intervention units—from 5.9% to 3.4% (OR=0.53, P<0.001)—but not in control units—from 8.7% to 8.5% (OR=0.98, P=0.71).

“Our study demonstrates that educating patients quickly, as soon as we learn about a missed dose, is not only possible to implement at a large hospital but is effective in ensuring that patients take the drugs that can save their lives,” Dr. Haut said.

“The educational bundles we created are effective and optimize busy clinicians’ already packed schedules,” added study author Brandyn Lau, of the Johns Hopkins University School of Medicine.

“At the end of the day, we’re here to deliver high quality care and keep patients safe, and this is one method of achieving that mission.”

However, the improved adherence to VTE prophylaxis did not translate to a significant reduction in VTE in this study.

The incidence of VTE decreased from 0.30% to 0.18% (OR=0.60) in intervention units and from 0.24% to 0.20% in control units (OR=0.81).

For all patients, the incidence of VTE was 0.26% pre-intervention and 0.19% post-intervention (P=0.46).

This research was supported by a contract from the Patient-Centered Outcomes Research Institute. The study authors reported support from various government agencies and private organizations.

Photo by Bill Branson

Long-term data suggest R-CHOP can be effective as first-line treatment for patients with follicular lymphoma (FL).

In a phase 2-3 trial, investigators compared R-CHOP-21 and R-CHOP-14 in a cohort of patients with indolent lymphomas, most of whom had FL.

Ten-year survival rates were similar between the R-CHOP-21 and R-CHOP-14 groups, with progression-free survival (PFS) rates of 33% and 39%, respectively, and overall survival (OS) rates of 81% and 85%, respectively.

The investigators did note that 9% of patients in each treatment group developed secondary malignancies, and grade 3 infections were a concern as well.

Takashi Watanabe, MD, PhD, of Mie University in Japan, and his colleagues reported these results in The Lancet Haematology.

The trial (JCOG0203) included 300 patients with stage III or IV indolent B-cell lymphomas from 44 Japanese hospitals.

Most patients (n=248) had grade 1-3a FL, 17 had grade 3b FL, 6 had marginal zone lymphoma, 6 had diffuse large B-cell lymphoma, 4 had mantle cell lymphoma, 2 had small lymphocytic lymphoma, 1 had plasmacytoma, 13 had other indolent B-cell lymphomas, and 3 had other lymphomas.

The patients were randomly assigned to receive six cycles of R-CHOP 21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone every 3 weeks) or R-CHOP 14 (R-CHOP every 2 weeks with granulocyte-colony stimulating factor support). Neither group received rituximab maintenance.

Overall results

The median follow-up was 11.2 years (interquartile range, 10.1 to 12.7 years).

The 10-year PFS was 33% in the R-CHOP-21 group and 39% in the R-CHOP-14 group (hazard ratio=0.89). The 10-year OS was 81% and 85%, respectively (hazard ratio=0.87).

At 10 years, the incidence of secondary malignancies was 9% in both the R-CHOP-21 group (14/148) and the R-CHOP-14 group (14/151).

The most frequent solid tumor malignancies were stomach (n=5), lung (n=4), colon (n=3), bladder (n=2), and prostate (n=2) cancers. Hematologic malignancies included myelodysplastic syndromes (n=6), acute myeloid leukemia (n=2), acute lymphoblastic leukemia (n=1), and chronic myeloid leukemia (n=1).

There were nine deaths from secondary malignancies, four in the R-CHOP-21 group and five in the R-CHOP-14 group.

The rate of grade 3 adverse events was 18% (n=53) for the entire cohort. Grade 3 infections occurred in 23% of the R-CHOP-21 group and 12% of the R-CHOP-14 group.

Focus on grade 1-3a FL

Among the 248 patients with grade 1-3a FL, the PFS (for both treatment groups) was 45% at 5 years, 39% at 8 years, and 36% at 10 years. The OS was 94% at 5 years, 87% at 8 years, and 85% at 10 years.

Histological transformation was observed in 11% of the patients who had grade 1-3a FL at enrollment. The cumulative incidence of histological transformation was 2.4% at 3 years, 3.2% at 5 years, 8.5% at 8 years, and 9.3% at 10 years.

Secondary malignancies occurred in 10% (12/125) of the R-CHOP-21 group and 11% (13/123) of the R-CHOP-14 group.

The cumulative incidence of hematologic secondary malignancies at 10 years was 2.9%.

The investigators noted that the actual incidence of secondary solid tumors or hematologic malignancies apart from the setting of autologous stem cell transplants is not known. They emphasized that patients should be followed beyond 10 years to ensure the risk of secondary malignancies is not underestimated.

“Clinicians choosing a first-line treatment for patients with follicular lymphoma should be cautious of secondary malignancies caused by immunochemotherapy and severe complications of infectious diseases in the long-term follow-up—both of which could lead to death,” the investigators wrote.

This study was supported by the Ministry of Health, Labour and Welfare of Japan and the National Cancer Center Research and Development Fund of Japan.

Dr. Wantanabe has received honoraria from Bristol-Myers Squibb, Takeda, Taisho Toyama, Celgene, Nippon Shinyaku, and Novartis and funding resources from TakaraBio and United Immunity to support the Department of Immuno-Gene Therapy at Mie University. Multiple co-authors reported similar relationships.

Photo by Bill Branson

Long-term data suggest R-CHOP can be effective as first-line treatment for patients with follicular lymphoma (FL).

In a phase 2-3 trial, investigators compared R-CHOP-21 and R-CHOP-14 in a cohort of patients with indolent lymphomas, most of whom had FL.

Ten-year survival rates were similar between the R-CHOP-21 and R-CHOP-14 groups, with progression-free survival (PFS) rates of 33% and 39%, respectively, and overall survival (OS) rates of 81% and 85%, respectively.

The investigators did note that 9% of patients in each treatment group developed secondary malignancies, and grade 3 infections were a concern as well.

Takashi Watanabe, MD, PhD, of Mie University in Japan, and his colleagues reported these results in The Lancet Haematology.

The trial (JCOG0203) included 300 patients with stage III or IV indolent B-cell lymphomas from 44 Japanese hospitals.

Most patients (n=248) had grade 1-3a FL, 17 had grade 3b FL, 6 had marginal zone lymphoma, 6 had diffuse large B-cell lymphoma, 4 had mantle cell lymphoma, 2 had small lymphocytic lymphoma, 1 had plasmacytoma, 13 had other indolent B-cell lymphomas, and 3 had other lymphomas.

The patients were randomly assigned to receive six cycles of R-CHOP 21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone every 3 weeks) or R-CHOP 14 (R-CHOP every 2 weeks with granulocyte-colony stimulating factor support). Neither group received rituximab maintenance.

Overall results

The median follow-up was 11.2 years (interquartile range, 10.1 to 12.7 years).

The 10-year PFS was 33% in the R-CHOP-21 group and 39% in the R-CHOP-14 group (hazard ratio=0.89). The 10-year OS was 81% and 85%, respectively (hazard ratio=0.87).

At 10 years, the incidence of secondary malignancies was 9% in both the R-CHOP-21 group (14/148) and the R-CHOP-14 group (14/151).

The most frequent solid tumor malignancies were stomach (n=5), lung (n=4), colon (n=3), bladder (n=2), and prostate (n=2) cancers. Hematologic malignancies included myelodysplastic syndromes (n=6), acute myeloid leukemia (n=2), acute lymphoblastic leukemia (n=1), and chronic myeloid leukemia (n=1).

There were nine deaths from secondary malignancies, four in the R-CHOP-21 group and five in the R-CHOP-14 group.

The rate of grade 3 adverse events was 18% (n=53) for the entire cohort. Grade 3 infections occurred in 23% of the R-CHOP-21 group and 12% of the R-CHOP-14 group.

Focus on grade 1-3a FL

Among the 248 patients with grade 1-3a FL, the PFS (for both treatment groups) was 45% at 5 years, 39% at 8 years, and 36% at 10 years. The OS was 94% at 5 years, 87% at 8 years, and 85% at 10 years.

Histological transformation was observed in 11% of the patients who had grade 1-3a FL at enrollment. The cumulative incidence of histological transformation was 2.4% at 3 years, 3.2% at 5 years, 8.5% at 8 years, and 9.3% at 10 years.

Secondary malignancies occurred in 10% (12/125) of the R-CHOP-21 group and 11% (13/123) of the R-CHOP-14 group.

The cumulative incidence of hematologic secondary malignancies at 10 years was 2.9%.

The investigators noted that the actual incidence of secondary solid tumors or hematologic malignancies apart from the setting of autologous stem cell transplants is not known. They emphasized that patients should be followed beyond 10 years to ensure the risk of secondary malignancies is not underestimated.

“Clinicians choosing a first-line treatment for patients with follicular lymphoma should be cautious of secondary malignancies caused by immunochemotherapy and severe complications of infectious diseases in the long-term follow-up—both of which could lead to death,” the investigators wrote.

This study was supported by the Ministry of Health, Labour and Welfare of Japan and the National Cancer Center Research and Development Fund of Japan.

Dr. Wantanabe has received honoraria from Bristol-Myers Squibb, Takeda, Taisho Toyama, Celgene, Nippon Shinyaku, and Novartis and funding resources from TakaraBio and United Immunity to support the Department of Immuno-Gene Therapy at Mie University. Multiple co-authors reported similar relationships.

Photo by Bill Branson

Long-term data suggest R-CHOP can be effective as first-line treatment for patients with follicular lymphoma (FL).

In a phase 2-3 trial, investigators compared R-CHOP-21 and R-CHOP-14 in a cohort of patients with indolent lymphomas, most of whom had FL.

Ten-year survival rates were similar between the R-CHOP-21 and R-CHOP-14 groups, with progression-free survival (PFS) rates of 33% and 39%, respectively, and overall survival (OS) rates of 81% and 85%, respectively.

The investigators did note that 9% of patients in each treatment group developed secondary malignancies, and grade 3 infections were a concern as well.

Takashi Watanabe, MD, PhD, of Mie University in Japan, and his colleagues reported these results in The Lancet Haematology.

The trial (JCOG0203) included 300 patients with stage III or IV indolent B-cell lymphomas from 44 Japanese hospitals.

Most patients (n=248) had grade 1-3a FL, 17 had grade 3b FL, 6 had marginal zone lymphoma, 6 had diffuse large B-cell lymphoma, 4 had mantle cell lymphoma, 2 had small lymphocytic lymphoma, 1 had plasmacytoma, 13 had other indolent B-cell lymphomas, and 3 had other lymphomas.

The patients were randomly assigned to receive six cycles of R-CHOP 21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone every 3 weeks) or R-CHOP 14 (R-CHOP every 2 weeks with granulocyte-colony stimulating factor support). Neither group received rituximab maintenance.

Overall results

The median follow-up was 11.2 years (interquartile range, 10.1 to 12.7 years).

The 10-year PFS was 33% in the R-CHOP-21 group and 39% in the R-CHOP-14 group (hazard ratio=0.89). The 10-year OS was 81% and 85%, respectively (hazard ratio=0.87).

At 10 years, the incidence of secondary malignancies was 9% in both the R-CHOP-21 group (14/148) and the R-CHOP-14 group (14/151).

The most frequent solid tumor malignancies were stomach (n=5), lung (n=4), colon (n=3), bladder (n=2), and prostate (n=2) cancers. Hematologic malignancies included myelodysplastic syndromes (n=6), acute myeloid leukemia (n=2), acute lymphoblastic leukemia (n=1), and chronic myeloid leukemia (n=1).

There were nine deaths from secondary malignancies, four in the R-CHOP-21 group and five in the R-CHOP-14 group.

The rate of grade 3 adverse events was 18% (n=53) for the entire cohort. Grade 3 infections occurred in 23% of the R-CHOP-21 group and 12% of the R-CHOP-14 group.

Focus on grade 1-3a FL

Among the 248 patients with grade 1-3a FL, the PFS (for both treatment groups) was 45% at 5 years, 39% at 8 years, and 36% at 10 years. The OS was 94% at 5 years, 87% at 8 years, and 85% at 10 years.

Histological transformation was observed in 11% of the patients who had grade 1-3a FL at enrollment. The cumulative incidence of histological transformation was 2.4% at 3 years, 3.2% at 5 years, 8.5% at 8 years, and 9.3% at 10 years.

Secondary malignancies occurred in 10% (12/125) of the R-CHOP-21 group and 11% (13/123) of the R-CHOP-14 group.

The cumulative incidence of hematologic secondary malignancies at 10 years was 2.9%.

The investigators noted that the actual incidence of secondary solid tumors or hematologic malignancies apart from the setting of autologous stem cell transplants is not known. They emphasized that patients should be followed beyond 10 years to ensure the risk of secondary malignancies is not underestimated.

“Clinicians choosing a first-line treatment for patients with follicular lymphoma should be cautious of secondary malignancies caused by immunochemotherapy and severe complications of infectious diseases in the long-term follow-up—both of which could lead to death,” the investigators wrote.

This study was supported by the Ministry of Health, Labour and Welfare of Japan and the National Cancer Center Research and Development Fund of Japan.

Dr. Wantanabe has received honoraria from Bristol-Myers Squibb, Takeda, Taisho Toyama, Celgene, Nippon Shinyaku, and Novartis and funding resources from TakaraBio and United Immunity to support the Department of Immuno-Gene Therapy at Mie University. Multiple co-authors reported similar relationships.