Leukemia, Myelodysplasia, Transplantation

Photo by Bill Branson

Childhood cancer survivors (CCSs) who were diagnosed in the 1990s have a lower risk of subsequent malignancies than CCSs diagnosed in the 1970s, according to research published in JAMA.

The data suggest this outcome is associated with a reduction in the overall use and median dose of therapeutic radiation over time.

Past research has shown an association between therapeutic radiation and the development of subsequent neoplasms in CCSs. Studies have also linked specific chemotherapeutic agents to subsequent neoplasms.

This information has been used to modify childhood cancer treatment over time, with the hope of reducing the risk of subsequent neoplasms while maintaining or improving 5-year survival.

To assess the effects of these treatment modifications, Gregory Armstrong, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues conducted a study of CCSs.

The researchers evaluated 23,603 five-year CCSs (mean age at diagnosis, 7.7 years) treated at pediatric hospitals in the US and Canada from 1970 through 1999, with follow-up through December 2015.

The most common initial diagnoses were acute lymphoblastic leukemia (35.1%), Hodgkin lymphoma (11.1%), and astrocytoma (9.6%).

Subsequent neoplasms, malignancies

At a mean follow-up of 20.5 years, 1639 CCSs had experienced 3115 subsequent neoplasms, including 1026 malignancies, 233 benign meningiomas, and 1856 non-melanoma skin cancers. The most common neoplasms were breast and thyroid cancers.

The 15-year cumulative incidence of subsequent neoplasms decreased by decade of diagnosis. The incidence was 2.9% for patients diagnosed in the 1970s, 2.4% for those diagnosed in the ’80s, and 1.5% for those diagnosed in the ’90s. For the 1970s vs 1980s, the P value was 0.02. For the 1970s vs 1990s and for the 1980s vs 1990s, the P value was <0.001.

The 15-year cumulative incidence of subsequent malignancies also decreased by decade of diagnosis—2.1% for the ’70s, 1.7% for the ’80s, and 1.3% for the ’90s. The P value was <0.001 for the ’70s vs the ’90s and the ’80s vs the ’90s.

Risk factors

In multivariable analyses, female CCSs had a higher rate of subsequent neoplasms (including malignancies) than males.

In addition, high doses of alkylating agents and platinum agents were associated with increased rates of subsequent malignancies.

The researchers noted that, although there was a decrease in the median cumulative dose of alkylating agents over time, the proportion of CCSs receiving these agents increased. And both the median cumulative dose of platinum agents and the proportion of CCSs receiving these agents increased from the ’70s to the ’90s.

Finally, therapeutic radiation was associated with increased rates of subsequent malignant neoplasms, meningiomas, and non-melanoma skin cancers.

This corresponded with the researchers’ findings that the proportion of individuals receiving radiation and the median dose of radiation both decreased over time.

The proportion of individuals receiving any radiation therapy was 77.7% in the ’70s, 56.7% in the ’80s, and 36.8% in the ’90s. The median dose of radiation was 30.0 Gy in the ’70s, 24.0 Gy in the ’80s, and 26.0 Gy in the ’90s.

“The most ominous late effect of pediatric cancer treatment is a second malignancy,” Dr Armstrong said. “This study shows efforts to reduce the late effects of treatment are paying off. The risk of second cancers for survivors increases with age, so it is good to see the reduction emerging early in survivorship while survivors are still young.”

Photo by Bill Branson

Childhood cancer survivors (CCSs) who were diagnosed in the 1990s have a lower risk of subsequent malignancies than CCSs diagnosed in the 1970s, according to research published in JAMA.

The data suggest this outcome is associated with a reduction in the overall use and median dose of therapeutic radiation over time.

Past research has shown an association between therapeutic radiation and the development of subsequent neoplasms in CCSs. Studies have also linked specific chemotherapeutic agents to subsequent neoplasms.

This information has been used to modify childhood cancer treatment over time, with the hope of reducing the risk of subsequent neoplasms while maintaining or improving 5-year survival.

To assess the effects of these treatment modifications, Gregory Armstrong, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues conducted a study of CCSs.

The researchers evaluated 23,603 five-year CCSs (mean age at diagnosis, 7.7 years) treated at pediatric hospitals in the US and Canada from 1970 through 1999, with follow-up through December 2015.

The most common initial diagnoses were acute lymphoblastic leukemia (35.1%), Hodgkin lymphoma (11.1%), and astrocytoma (9.6%).

Subsequent neoplasms, malignancies

At a mean follow-up of 20.5 years, 1639 CCSs had experienced 3115 subsequent neoplasms, including 1026 malignancies, 233 benign meningiomas, and 1856 non-melanoma skin cancers. The most common neoplasms were breast and thyroid cancers.

The 15-year cumulative incidence of subsequent neoplasms decreased by decade of diagnosis. The incidence was 2.9% for patients diagnosed in the 1970s, 2.4% for those diagnosed in the ’80s, and 1.5% for those diagnosed in the ’90s. For the 1970s vs 1980s, the P value was 0.02. For the 1970s vs 1990s and for the 1980s vs 1990s, the P value was <0.001.

The 15-year cumulative incidence of subsequent malignancies also decreased by decade of diagnosis—2.1% for the ’70s, 1.7% for the ’80s, and 1.3% for the ’90s. The P value was <0.001 for the ’70s vs the ’90s and the ’80s vs the ’90s.

Risk factors

In multivariable analyses, female CCSs had a higher rate of subsequent neoplasms (including malignancies) than males.

In addition, high doses of alkylating agents and platinum agents were associated with increased rates of subsequent malignancies.

The researchers noted that, although there was a decrease in the median cumulative dose of alkylating agents over time, the proportion of CCSs receiving these agents increased. And both the median cumulative dose of platinum agents and the proportion of CCSs receiving these agents increased from the ’70s to the ’90s.

Finally, therapeutic radiation was associated with increased rates of subsequent malignant neoplasms, meningiomas, and non-melanoma skin cancers.

This corresponded with the researchers’ findings that the proportion of individuals receiving radiation and the median dose of radiation both decreased over time.

The proportion of individuals receiving any radiation therapy was 77.7% in the ’70s, 56.7% in the ’80s, and 36.8% in the ’90s. The median dose of radiation was 30.0 Gy in the ’70s, 24.0 Gy in the ’80s, and 26.0 Gy in the ’90s.

“The most ominous late effect of pediatric cancer treatment is a second malignancy,” Dr Armstrong said. “This study shows efforts to reduce the late effects of treatment are paying off. The risk of second cancers for survivors increases with age, so it is good to see the reduction emerging early in survivorship while survivors are still young.”

Photo by Bill Branson

Childhood cancer survivors (CCSs) who were diagnosed in the 1990s have a lower risk of subsequent malignancies than CCSs diagnosed in the 1970s, according to research published in JAMA.

The data suggest this outcome is associated with a reduction in the overall use and median dose of therapeutic radiation over time.

Past research has shown an association between therapeutic radiation and the development of subsequent neoplasms in CCSs. Studies have also linked specific chemotherapeutic agents to subsequent neoplasms.

This information has been used to modify childhood cancer treatment over time, with the hope of reducing the risk of subsequent neoplasms while maintaining or improving 5-year survival.

To assess the effects of these treatment modifications, Gregory Armstrong, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues conducted a study of CCSs.

The researchers evaluated 23,603 five-year CCSs (mean age at diagnosis, 7.7 years) treated at pediatric hospitals in the US and Canada from 1970 through 1999, with follow-up through December 2015.

The most common initial diagnoses were acute lymphoblastic leukemia (35.1%), Hodgkin lymphoma (11.1%), and astrocytoma (9.6%).

Subsequent neoplasms, malignancies

At a mean follow-up of 20.5 years, 1639 CCSs had experienced 3115 subsequent neoplasms, including 1026 malignancies, 233 benign meningiomas, and 1856 non-melanoma skin cancers. The most common neoplasms were breast and thyroid cancers.

The 15-year cumulative incidence of subsequent neoplasms decreased by decade of diagnosis. The incidence was 2.9% for patients diagnosed in the 1970s, 2.4% for those diagnosed in the ’80s, and 1.5% for those diagnosed in the ’90s. For the 1970s vs 1980s, the P value was 0.02. For the 1970s vs 1990s and for the 1980s vs 1990s, the P value was <0.001.

The 15-year cumulative incidence of subsequent malignancies also decreased by decade of diagnosis—2.1% for the ’70s, 1.7% for the ’80s, and 1.3% for the ’90s. The P value was <0.001 for the ’70s vs the ’90s and the ’80s vs the ’90s.

Risk factors

In multivariable analyses, female CCSs had a higher rate of subsequent neoplasms (including malignancies) than males.

In addition, high doses of alkylating agents and platinum agents were associated with increased rates of subsequent malignancies.

The researchers noted that, although there was a decrease in the median cumulative dose of alkylating agents over time, the proportion of CCSs receiving these agents increased. And both the median cumulative dose of platinum agents and the proportion of CCSs receiving these agents increased from the ’70s to the ’90s.

Finally, therapeutic radiation was associated with increased rates of subsequent malignant neoplasms, meningiomas, and non-melanoma skin cancers.

This corresponded with the researchers’ findings that the proportion of individuals receiving radiation and the median dose of radiation both decreased over time.

The proportion of individuals receiving any radiation therapy was 77.7% in the ’70s, 56.7% in the ’80s, and 36.8% in the ’90s. The median dose of radiation was 30.0 Gy in the ’70s, 24.0 Gy in the ’80s, and 26.0 Gy in the ’90s.

“The most ominous late effect of pediatric cancer treatment is a second malignancy,” Dr Armstrong said. “This study shows efforts to reduce the late effects of treatment are paying off. The risk of second cancers for survivors increases with age, so it is good to see the reduction emerging early in survivorship while survivors are still young.”

Photo by Bill Branson

ORLANDO, FL—Results of a phase 3 trial suggest an inactivated varicella zoster virus (VZV) vaccine known as V212 can reduce the risk of herpes zoster (HZ) in patients who have undergone autologous hematopoietic stem cell transplant (HSCT).

V212 reduced the hazard rate of HZ by an estimated 64% compared to placebo.

The vaccine also reduced the incidence of moderate-to-severe HZ pain and other HZ-related complications, such as hospitalization.

The overall incidence of adverse events (AEs) and the incidence of serious AEs were similar among vaccinated patients and those who received placebo.

Drew J. Winston, MD, of the University of California Los Angeles Medical Center, presented these results as one of the “Best Abstracts” at the 2017 BMT Tandem Meetings (abstract 6). The trial was sponsored by Merck, the company developing V212.

Treatment

This randomized, double-blind trial enrolled 1230 patients age 18 and older who were undergoing HSCT for any indication and had a history of varicella infection and/or were seropositive for VZV antibody.

The patients were randomized to receive:

• A 4-dose regimen of V212 (n=560) from a consistency lot (a lot having a targeted potency as required by regulators in order to demonstrate that the vaccine can be manufactured consistently)
• A 4-dose regimen of V212 (n=106) from a high-antigen lot (a lot having a higher antigen potency added to assess the safety profile of V212)
• Placebo (n=564).

Randomization was stratified by age (< 50 years vs ≥ 50 years) and by intended duration of post-transplant antiviral prophylaxis (≤3 months vs >3 to 6 months).

Dose 1 of V212 or placebo was given within approximately 30 days before HSCT, and doses 2, 3, and 4 were given approximately 30, 60, and 90 days after HSCT.

Patient characteristics

The median patient age was 57 (range, 19-76) for the consistency lot group, 56 (range, 21-75) for the high-antigen lot group, and 56 (range, 19-79) for the placebo group.

Underlying diseases were non-Hodgkin lymphoma (42%, 40%, and 44%, respectively), Hodgkin lymphoma (10%, 9%, and 9%, respectively), multiple myeloma (44%, 47% and 41%, respectively), acute leukemia (2%, 1%, and 2%, respectively), and “other” diseases (2%, 3% and 4%, respectively).

Roughly 30% of patients in each group received anti-viral agents for 3 months or less after HSCT. Twenty percent to 25% received antiviral therapy for more than 3 months to 6 months.

Thirty-seven percent to 40% received antiviral agents for more than 6 months. And 7% to 12% of patients did not receive any antiviral therapy.

HZ incidence

The average follow-up time for HZ surveillance was approximately 2.3 years (median: 2.6 years) post-vaccination.

Confirmed HZ occurred in 42 of the 538 patients who received V212 from a consistency lot and 113 of the 535 patients who received placebo. (Patients receiving V212 from a high-antigen lot were only included in the safety analysis.)

The estimated efficacy of V212 was 63.8% after adjustment for patient age and the duration of antiviral prophylaxis. Vaccine efficacy against HZ was defined as the relative reduction of hazard rate of HZ in vaccine recipients compared with placebo recipients.

The vaccine met the pre-specified criterion for success, as the lower bound of the 95% confidence interval (CI) was greater than 25%. The 95% CI was 48.4% to 74.6% (P<0.0001).

“The study demonstrates that the inactivated varicella vaccine is very effective for preventing herpes zoster after autologous stem cell transplantation,” Dr Winston said.

Pain, PHN, and other complications

V212 also reduced the incidence of moderate-to-severe HZ pain—according to the Zoster Brief Pain Inventory (ZBPI) score—by an estimated 69.5% (95% CI, 0.490-0.818).

Nineteen patients in the V212 consistency lot group had moderate-to-severe pain, as did 61 placebo-treated patients.

V212 conferred an estimated 83.7% (95% CI, 0.446-0.952) reduction in the incidence of post-herpetic neuralgia (PHN). Three patients in the V212 consistency lot group and 18 patients in the placebo group had PHN.

PHN was defined as pain in the area of the HZ rash with a “worst pain in the last 24 hours” score of 3 or greater (on a 0-10 scale) on the ZBPI that persists or appears 90 days or beyond after HZ rash onset following HSCT.

Patients who received V212 also saw an estimated 73.5% (95% CI, 0.498-0.860) reduction in “other” HZ complications. Twelve patients in the V212 consistency group and 44 in the placebo group had such complications.

“Other” complications included hospitalization or prolongation of hospitalization due to HZ, disseminated HZ (including disseminated HZ rash or VZV viremia), visceral HZ, ophthalmic HZ, neurological impairment due to HZ, and the administration of intravenous acyclovir therapy for the treatment of HZ post-HSCT.

Safety

All patients who received at least 1 dose of the vaccine or placebo and had follow-up data were included in the safety analysis. Patients were followed for AEs up to 28 days after the fourth vaccination dose.

AEs occurred in 97% of patients who received the vaccine (consistency and high-antigen groups assessed together) and 96.9% of placebo-treated patients. Vaccine-related AEs occurred in 32.6% and 12.6%, respectively.

“Of course, in this population of autologous stem cell transplant patients, adverse events of any type were very common in almost all patients,” Dr Winston said. “However, vaccine-related adverse events were greater in the vaccine recipients compared to the placebo patients, but this was primarily due to an increased incidence of injection-site adverse events in the vaccine recipients.”

Injection-site reactions occurred in 191 vaccinated patients and 36 placebo-treated patients.

The most common systemic AEs—in vaccinated and placebo-treated patients, respectively—were diarrhea (60.1% and 61.9%), nausea (56.5% and 57.8%), pyrexia (49.8% and 46.9%), mucosal inflammation (39.7% and 41.7%), thrombocytopenia (36.4% and 38.4%), febrile neutropenia (33.9% and 28.3%), vomiting (32.6% and 36.6%), anemia (26.6% and 24.4%), neutropenia (25.1% and 23.5%), decreased appetite (23.1% and 23.8%), fatigue (21.8% and 20.7%), hypokalemia (21.3% and 19.9%), and constipation (16.1% and 18.4%).

The incidence of serious AEs was 32.9% in vaccinated patients and 32.7% in the placebo group. The incidence of serious vaccine-related AEs was 0.8% and 0.9%, respectively.

The most common serious AEs—in vaccinated and placebo-treated patients, respectively—were infection (12.3% and 11.9%), relapsed malignancy (7.8% for both), febrile neutropenia (5.3% and 4.9%), pyrexia (3.2% and 4.0%), gastrointestinal disorders (3.2% and 3.6%), respiratory failure (2.7% and 2.2%), cardiac disorders (1.7% and 1.6%), and mucositis (1.2% and 0.9%).

Death occurred in 6.2% of vaccinated patients and 6.3% of placebo-treated patients. Three percent and 3.1%, respectively, discontinued the study due to AEs.

Photo by Bill Branson

ORLANDO, FL—Results of a phase 3 trial suggest an inactivated varicella zoster virus (VZV) vaccine known as V212 can reduce the risk of herpes zoster (HZ) in patients who have undergone autologous hematopoietic stem cell transplant (HSCT).

V212 reduced the hazard rate of HZ by an estimated 64% compared to placebo.

The vaccine also reduced the incidence of moderate-to-severe HZ pain and other HZ-related complications, such as hospitalization.

The overall incidence of adverse events (AEs) and the incidence of serious AEs were similar among vaccinated patients and those who received placebo.

Drew J. Winston, MD, of the University of California Los Angeles Medical Center, presented these results as one of the “Best Abstracts” at the 2017 BMT Tandem Meetings (abstract 6). The trial was sponsored by Merck, the company developing V212.

Treatment

This randomized, double-blind trial enrolled 1230 patients age 18 and older who were undergoing HSCT for any indication and had a history of varicella infection and/or were seropositive for VZV antibody.

The patients were randomized to receive:

• A 4-dose regimen of V212 (n=560) from a consistency lot (a lot having a targeted potency as required by regulators in order to demonstrate that the vaccine can be manufactured consistently)
• A 4-dose regimen of V212 (n=106) from a high-antigen lot (a lot having a higher antigen potency added to assess the safety profile of V212)
• Placebo (n=564).

Randomization was stratified by age (< 50 years vs ≥ 50 years) and by intended duration of post-transplant antiviral prophylaxis (≤3 months vs >3 to 6 months).

Dose 1 of V212 or placebo was given within approximately 30 days before HSCT, and doses 2, 3, and 4 were given approximately 30, 60, and 90 days after HSCT.

Patient characteristics

The median patient age was 57 (range, 19-76) for the consistency lot group, 56 (range, 21-75) for the high-antigen lot group, and 56 (range, 19-79) for the placebo group.

Underlying diseases were non-Hodgkin lymphoma (42%, 40%, and 44%, respectively), Hodgkin lymphoma (10%, 9%, and 9%, respectively), multiple myeloma (44%, 47% and 41%, respectively), acute leukemia (2%, 1%, and 2%, respectively), and “other” diseases (2%, 3% and 4%, respectively).

Roughly 30% of patients in each group received anti-viral agents for 3 months or less after HSCT. Twenty percent to 25% received antiviral therapy for more than 3 months to 6 months.

Thirty-seven percent to 40% received antiviral agents for more than 6 months. And 7% to 12% of patients did not receive any antiviral therapy.

HZ incidence

The average follow-up time for HZ surveillance was approximately 2.3 years (median: 2.6 years) post-vaccination.

Confirmed HZ occurred in 42 of the 538 patients who received V212 from a consistency lot and 113 of the 535 patients who received placebo. (Patients receiving V212 from a high-antigen lot were only included in the safety analysis.)

The estimated efficacy of V212 was 63.8% after adjustment for patient age and the duration of antiviral prophylaxis. Vaccine efficacy against HZ was defined as the relative reduction of hazard rate of HZ in vaccine recipients compared with placebo recipients.

The vaccine met the pre-specified criterion for success, as the lower bound of the 95% confidence interval (CI) was greater than 25%. The 95% CI was 48.4% to 74.6% (P<0.0001).

“The study demonstrates that the inactivated varicella vaccine is very effective for preventing herpes zoster after autologous stem cell transplantation,” Dr Winston said.

Pain, PHN, and other complications

V212 also reduced the incidence of moderate-to-severe HZ pain—according to the Zoster Brief Pain Inventory (ZBPI) score—by an estimated 69.5% (95% CI, 0.490-0.818).

Nineteen patients in the V212 consistency lot group had moderate-to-severe pain, as did 61 placebo-treated patients.

V212 conferred an estimated 83.7% (95% CI, 0.446-0.952) reduction in the incidence of post-herpetic neuralgia (PHN). Three patients in the V212 consistency lot group and 18 patients in the placebo group had PHN.

PHN was defined as pain in the area of the HZ rash with a “worst pain in the last 24 hours” score of 3 or greater (on a 0-10 scale) on the ZBPI that persists or appears 90 days or beyond after HZ rash onset following HSCT.

Patients who received V212 also saw an estimated 73.5% (95% CI, 0.498-0.860) reduction in “other” HZ complications. Twelve patients in the V212 consistency group and 44 in the placebo group had such complications.

“Other” complications included hospitalization or prolongation of hospitalization due to HZ, disseminated HZ (including disseminated HZ rash or VZV viremia), visceral HZ, ophthalmic HZ, neurological impairment due to HZ, and the administration of intravenous acyclovir therapy for the treatment of HZ post-HSCT.

Safety

All patients who received at least 1 dose of the vaccine or placebo and had follow-up data were included in the safety analysis. Patients were followed for AEs up to 28 days after the fourth vaccination dose.

AEs occurred in 97% of patients who received the vaccine (consistency and high-antigen groups assessed together) and 96.9% of placebo-treated patients. Vaccine-related AEs occurred in 32.6% and 12.6%, respectively.

“Of course, in this population of autologous stem cell transplant patients, adverse events of any type were very common in almost all patients,” Dr Winston said. “However, vaccine-related adverse events were greater in the vaccine recipients compared to the placebo patients, but this was primarily due to an increased incidence of injection-site adverse events in the vaccine recipients.”

Injection-site reactions occurred in 191 vaccinated patients and 36 placebo-treated patients.

The most common systemic AEs—in vaccinated and placebo-treated patients, respectively—were diarrhea (60.1% and 61.9%), nausea (56.5% and 57.8%), pyrexia (49.8% and 46.9%), mucosal inflammation (39.7% and 41.7%), thrombocytopenia (36.4% and 38.4%), febrile neutropenia (33.9% and 28.3%), vomiting (32.6% and 36.6%), anemia (26.6% and 24.4%), neutropenia (25.1% and 23.5%), decreased appetite (23.1% and 23.8%), fatigue (21.8% and 20.7%), hypokalemia (21.3% and 19.9%), and constipation (16.1% and 18.4%).

The incidence of serious AEs was 32.9% in vaccinated patients and 32.7% in the placebo group. The incidence of serious vaccine-related AEs was 0.8% and 0.9%, respectively.

The most common serious AEs—in vaccinated and placebo-treated patients, respectively—were infection (12.3% and 11.9%), relapsed malignancy (7.8% for both), febrile neutropenia (5.3% and 4.9%), pyrexia (3.2% and 4.0%), gastrointestinal disorders (3.2% and 3.6%), respiratory failure (2.7% and 2.2%), cardiac disorders (1.7% and 1.6%), and mucositis (1.2% and 0.9%).

Death occurred in 6.2% of vaccinated patients and 6.3% of placebo-treated patients. Three percent and 3.1%, respectively, discontinued the study due to AEs.

Photo by Bill Branson

ORLANDO, FL—Results of a phase 3 trial suggest an inactivated varicella zoster virus (VZV) vaccine known as V212 can reduce the risk of herpes zoster (HZ) in patients who have undergone autologous hematopoietic stem cell transplant (HSCT).

V212 reduced the hazard rate of HZ by an estimated 64% compared to placebo.

The vaccine also reduced the incidence of moderate-to-severe HZ pain and other HZ-related complications, such as hospitalization.

The overall incidence of adverse events (AEs) and the incidence of serious AEs were similar among vaccinated patients and those who received placebo.

Drew J. Winston, MD, of the University of California Los Angeles Medical Center, presented these results as one of the “Best Abstracts” at the 2017 BMT Tandem Meetings (abstract 6). The trial was sponsored by Merck, the company developing V212.

Treatment

This randomized, double-blind trial enrolled 1230 patients age 18 and older who were undergoing HSCT for any indication and had a history of varicella infection and/or were seropositive for VZV antibody.

The patients were randomized to receive:

• A 4-dose regimen of V212 (n=560) from a consistency lot (a lot having a targeted potency as required by regulators in order to demonstrate that the vaccine can be manufactured consistently)
• A 4-dose regimen of V212 (n=106) from a high-antigen lot (a lot having a higher antigen potency added to assess the safety profile of V212)
• Placebo (n=564).

Randomization was stratified by age (< 50 years vs ≥ 50 years) and by intended duration of post-transplant antiviral prophylaxis (≤3 months vs >3 to 6 months).

Dose 1 of V212 or placebo was given within approximately 30 days before HSCT, and doses 2, 3, and 4 were given approximately 30, 60, and 90 days after HSCT.

Patient characteristics

The median patient age was 57 (range, 19-76) for the consistency lot group, 56 (range, 21-75) for the high-antigen lot group, and 56 (range, 19-79) for the placebo group.

Underlying diseases were non-Hodgkin lymphoma (42%, 40%, and 44%, respectively), Hodgkin lymphoma (10%, 9%, and 9%, respectively), multiple myeloma (44%, 47% and 41%, respectively), acute leukemia (2%, 1%, and 2%, respectively), and “other” diseases (2%, 3% and 4%, respectively).

Roughly 30% of patients in each group received anti-viral agents for 3 months or less after HSCT. Twenty percent to 25% received antiviral therapy for more than 3 months to 6 months.

Thirty-seven percent to 40% received antiviral agents for more than 6 months. And 7% to 12% of patients did not receive any antiviral therapy.

HZ incidence

The average follow-up time for HZ surveillance was approximately 2.3 years (median: 2.6 years) post-vaccination.

Confirmed HZ occurred in 42 of the 538 patients who received V212 from a consistency lot and 113 of the 535 patients who received placebo. (Patients receiving V212 from a high-antigen lot were only included in the safety analysis.)

The estimated efficacy of V212 was 63.8% after adjustment for patient age and the duration of antiviral prophylaxis. Vaccine efficacy against HZ was defined as the relative reduction of hazard rate of HZ in vaccine recipients compared with placebo recipients.

The vaccine met the pre-specified criterion for success, as the lower bound of the 95% confidence interval (CI) was greater than 25%. The 95% CI was 48.4% to 74.6% (P<0.0001).

“The study demonstrates that the inactivated varicella vaccine is very effective for preventing herpes zoster after autologous stem cell transplantation,” Dr Winston said.

Pain, PHN, and other complications

V212 also reduced the incidence of moderate-to-severe HZ pain—according to the Zoster Brief Pain Inventory (ZBPI) score—by an estimated 69.5% (95% CI, 0.490-0.818).

Nineteen patients in the V212 consistency lot group had moderate-to-severe pain, as did 61 placebo-treated patients.

V212 conferred an estimated 83.7% (95% CI, 0.446-0.952) reduction in the incidence of post-herpetic neuralgia (PHN). Three patients in the V212 consistency lot group and 18 patients in the placebo group had PHN.

PHN was defined as pain in the area of the HZ rash with a “worst pain in the last 24 hours” score of 3 or greater (on a 0-10 scale) on the ZBPI that persists or appears 90 days or beyond after HZ rash onset following HSCT.

Patients who received V212 also saw an estimated 73.5% (95% CI, 0.498-0.860) reduction in “other” HZ complications. Twelve patients in the V212 consistency group and 44 in the placebo group had such complications.

“Other” complications included hospitalization or prolongation of hospitalization due to HZ, disseminated HZ (including disseminated HZ rash or VZV viremia), visceral HZ, ophthalmic HZ, neurological impairment due to HZ, and the administration of intravenous acyclovir therapy for the treatment of HZ post-HSCT.

Safety

All patients who received at least 1 dose of the vaccine or placebo and had follow-up data were included in the safety analysis. Patients were followed for AEs up to 28 days after the fourth vaccination dose.

AEs occurred in 97% of patients who received the vaccine (consistency and high-antigen groups assessed together) and 96.9% of placebo-treated patients. Vaccine-related AEs occurred in 32.6% and 12.6%, respectively.

“Of course, in this population of autologous stem cell transplant patients, adverse events of any type were very common in almost all patients,” Dr Winston said. “However, vaccine-related adverse events were greater in the vaccine recipients compared to the placebo patients, but this was primarily due to an increased incidence of injection-site adverse events in the vaccine recipients.”

Injection-site reactions occurred in 191 vaccinated patients and 36 placebo-treated patients.

The most common systemic AEs—in vaccinated and placebo-treated patients, respectively—were diarrhea (60.1% and 61.9%), nausea (56.5% and 57.8%), pyrexia (49.8% and 46.9%), mucosal inflammation (39.7% and 41.7%), thrombocytopenia (36.4% and 38.4%), febrile neutropenia (33.9% and 28.3%), vomiting (32.6% and 36.6%), anemia (26.6% and 24.4%), neutropenia (25.1% and 23.5%), decreased appetite (23.1% and 23.8%), fatigue (21.8% and 20.7%), hypokalemia (21.3% and 19.9%), and constipation (16.1% and 18.4%).

The incidence of serious AEs was 32.9% in vaccinated patients and 32.7% in the placebo group. The incidence of serious vaccine-related AEs was 0.8% and 0.9%, respectively.

The most common serious AEs—in vaccinated and placebo-treated patients, respectively—were infection (12.3% and 11.9%), relapsed malignancy (7.8% for both), febrile neutropenia (5.3% and 4.9%), pyrexia (3.2% and 4.0%), gastrointestinal disorders (3.2% and 3.6%), respiratory failure (2.7% and 2.2%), cardiac disorders (1.7% and 1.6%), and mucositis (1.2% and 0.9%).

Death occurred in 6.2% of vaccinated patients and 6.3% of placebo-treated patients. Three percent and 3.1%, respectively, discontinued the study due to AEs.

Kristyna Wentz-Graff

A newly discovered issue with the Ba/F3 transformation assay could “jeopardize attempts to characterize the signaling mechanisms and drug sensitivities of leukemic oncogenes,” researchers reported in Oncotarget.

The researchers said the assay “remains an invaluable tool” for validating activating mutations in primary leukemias.

However, the assay is prone to a previously unreported flaw, where Ba/F3 cells can acquire additional mutations.

This issue was discovered by Kevin Watanabe-Smith, PhD, of Oregon Health & Science University in Portland.

He identified the problem while studying a growth-activating mutation in a patient with T-cell leukemia. (The results of that research were published in Leukemia in April 2016).

“When I was sequencing the patient’s DNA to make sure the original, known mutation is there, I was finding additional, unexpected mutations in the gene that I didn’t put there,” Dr Watanabe-Smith said. “And I was getting different mutations every time.”

“After we saw this in several cases, we knew it was worth further study,” added Cristina Tognon, PhD, of Oregon Health & Science University.

So the researchers decided to study Ba/F3 cell lines with and without 4 mutations (found in 3 cytokine receptors) that have “known transformative capacity,” including:

• CSF2RB R461C, a germline mutation found in a patient with T-cell acute lymphoblastic leukemia (ALL)
• CSF3R T618I, a mutation found in chronic neutrophilic leukemia (CNL) and atypical chronic myelogenous leukemia (aCML)
• CSF3R W791X, also found in CNL and aCML
• IL7R 243InsPPCL, which was found in a patient with B-cell ALL.

The researchers said they observed acquired mutations in 1 of 3 CSF2RB wild-type cell lines that transformed and all 4 CSF3R wild-type cell lines, which all transformed.

Furthermore, most CSF2RB R461C lines (4/5) and CSF3R W791X lines (3/4) had additional acquired mutations. However, the CSF3R T618I lines and the IL7R 243InsPPCL lines did not contain acquired mutations.

The researchers said acquired mutations were observed only in weakly transforming oncogenes, which were defined as mutations with a weaker ability to transform cells (less than 1 in every 200 cells) or a slower time to outgrowth (5 days or longer to reach a 5-fold increase over the initial cell number).

The team also said their findings indicate that the majority of the acquired mutations likely exist before IL-3 withdrawal but only expand to levels detectable by Sanger sequencing in the absence of IL-3.

“The potential impact [of these acquired mutations] is that a non-functional mutation could appear functional, and a researcher could publish results that would not be reproducible,” Dr Watanabe-Smith said.

To overcome this problem, Dr Watanabe-Smith and his colleagues recommended taking an additional step when using the Ba/F3 assay—sequencing outgrown cell lines. They also said additional research is needed to devise methods that reduce the incidence of acquired mutations in such assays. 

Kristyna Wentz-Graff

A newly discovered issue with the Ba/F3 transformation assay could “jeopardize attempts to characterize the signaling mechanisms and drug sensitivities of leukemic oncogenes,” researchers reported in Oncotarget.

The researchers said the assay “remains an invaluable tool” for validating activating mutations in primary leukemias.

However, the assay is prone to a previously unreported flaw, where Ba/F3 cells can acquire additional mutations.

This issue was discovered by Kevin Watanabe-Smith, PhD, of Oregon Health & Science University in Portland.

He identified the problem while studying a growth-activating mutation in a patient with T-cell leukemia. (The results of that research were published in Leukemia in April 2016).

“When I was sequencing the patient’s DNA to make sure the original, known mutation is there, I was finding additional, unexpected mutations in the gene that I didn’t put there,” Dr Watanabe-Smith said. “And I was getting different mutations every time.”

“After we saw this in several cases, we knew it was worth further study,” added Cristina Tognon, PhD, of Oregon Health & Science University.

So the researchers decided to study Ba/F3 cell lines with and without 4 mutations (found in 3 cytokine receptors) that have “known transformative capacity,” including:

• CSF2RB R461C, a germline mutation found in a patient with T-cell acute lymphoblastic leukemia (ALL)
• CSF3R T618I, a mutation found in chronic neutrophilic leukemia (CNL) and atypical chronic myelogenous leukemia (aCML)
• CSF3R W791X, also found in CNL and aCML
• IL7R 243InsPPCL, which was found in a patient with B-cell ALL.

The researchers said they observed acquired mutations in 1 of 3 CSF2RB wild-type cell lines that transformed and all 4 CSF3R wild-type cell lines, which all transformed.

Furthermore, most CSF2RB R461C lines (4/5) and CSF3R W791X lines (3/4) had additional acquired mutations. However, the CSF3R T618I lines and the IL7R 243InsPPCL lines did not contain acquired mutations.

The researchers said acquired mutations were observed only in weakly transforming oncogenes, which were defined as mutations with a weaker ability to transform cells (less than 1 in every 200 cells) or a slower time to outgrowth (5 days or longer to reach a 5-fold increase over the initial cell number).

The team also said their findings indicate that the majority of the acquired mutations likely exist before IL-3 withdrawal but only expand to levels detectable by Sanger sequencing in the absence of IL-3.

“The potential impact [of these acquired mutations] is that a non-functional mutation could appear functional, and a researcher could publish results that would not be reproducible,” Dr Watanabe-Smith said.

To overcome this problem, Dr Watanabe-Smith and his colleagues recommended taking an additional step when using the Ba/F3 assay—sequencing outgrown cell lines. They also said additional research is needed to devise methods that reduce the incidence of acquired mutations in such assays. 

Kristyna Wentz-Graff

A newly discovered issue with the Ba/F3 transformation assay could “jeopardize attempts to characterize the signaling mechanisms and drug sensitivities of leukemic oncogenes,” researchers reported in Oncotarget.

The researchers said the assay “remains an invaluable tool” for validating activating mutations in primary leukemias.

However, the assay is prone to a previously unreported flaw, where Ba/F3 cells can acquire additional mutations.

This issue was discovered by Kevin Watanabe-Smith, PhD, of Oregon Health & Science University in Portland.

He identified the problem while studying a growth-activating mutation in a patient with T-cell leukemia. (The results of that research were published in Leukemia in April 2016).

“When I was sequencing the patient’s DNA to make sure the original, known mutation is there, I was finding additional, unexpected mutations in the gene that I didn’t put there,” Dr Watanabe-Smith said. “And I was getting different mutations every time.”

“After we saw this in several cases, we knew it was worth further study,” added Cristina Tognon, PhD, of Oregon Health & Science University.

So the researchers decided to study Ba/F3 cell lines with and without 4 mutations (found in 3 cytokine receptors) that have “known transformative capacity,” including:

• CSF2RB R461C, a germline mutation found in a patient with T-cell acute lymphoblastic leukemia (ALL)
• CSF3R T618I, a mutation found in chronic neutrophilic leukemia (CNL) and atypical chronic myelogenous leukemia (aCML)
• CSF3R W791X, also found in CNL and aCML
• IL7R 243InsPPCL, which was found in a patient with B-cell ALL.

The researchers said they observed acquired mutations in 1 of 3 CSF2RB wild-type cell lines that transformed and all 4 CSF3R wild-type cell lines, which all transformed.

Furthermore, most CSF2RB R461C lines (4/5) and CSF3R W791X lines (3/4) had additional acquired mutations. However, the CSF3R T618I lines and the IL7R 243InsPPCL lines did not contain acquired mutations.

The researchers said acquired mutations were observed only in weakly transforming oncogenes, which were defined as mutations with a weaker ability to transform cells (less than 1 in every 200 cells) or a slower time to outgrowth (5 days or longer to reach a 5-fold increase over the initial cell number).

The team also said their findings indicate that the majority of the acquired mutations likely exist before IL-3 withdrawal but only expand to levels detectable by Sanger sequencing in the absence of IL-3.

“The potential impact [of these acquired mutations] is that a non-functional mutation could appear functional, and a researcher could publish results that would not be reproducible,” Dr Watanabe-Smith said.

To overcome this problem, Dr Watanabe-Smith and his colleagues recommended taking an additional step when using the Ba/F3 assay—sequencing outgrown cell lines. They also said additional research is needed to devise methods that reduce the incidence of acquired mutations in such assays. 

Photo courtesy of CDC

ORLANDO, FL—New research shows that patients who received inpatient palliative care while undergoing hematopoietic stem cell transplant (HSCT) experienced significant improvements in quality of life (QOL), decreases in depression, and reductions in symptom burden compared to patients who received transplant care alone.

Areej R. El-Jawahri, MD, of Harvard Medical School in Boston, Massachusetts, presented these results at the 2017 BMT Tandem Meetings (abstract 49).

She noted that palliative care is rarely used for patients with hematologic malignancies, “in part, because of misperceptions equating palliative care with just end-of-life care.”

So Dr El-Jawahri and her colleagues decided to evaluate palliative care in patients with hematologic malignancies who were scheduled to undergo HSCT.

The researchers enrolled 160 patients on the trial. Eighty-one were randomized to receive inpatient palliative care integrated with transplant care (intervention arm), and 79 were randomized to transplant care alone (control).

The latter group could request palliative care consultations, but only 2 patients did so, Dr El-Jawahri pointed out.

Patients receiving the intervention had at least twice-weekly visits with a palliative care clinician throughout their hospitalization.

“Importantly, palliative care only followed patients during their transplant hospitalization,” Dr El-Jawahri noted. “This was purely an inpatient palliative care intervention.”

Palliative care focused primarily on managing patients’ symptoms, establishing rapport with patients and families, and helping them cope with their illness. The predominant symptoms addressed included pain, nausea, diarrhea, constipation, insomnia, fatigue, depression, and anxiety.

Researchers assessed QOL, symptom burden, and mood at baseline, during hospitalization (Week 2), and at 3 and 6 months using well-validated scales.

They assessed QOL using the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) scale, mood using the Hospital Anxiety and Depression Scale (HADS) and Patient Health Questionnaire (PHQ-9), and symptom burden using the Edmonton Symptom Assessment Scale (ESAS).

They also measured post-traumatic stress (PTSD) at baseline as well as 3 and 6 months after HSCT using the PTSD checklist.

The primary endpoint of the study was patient-reported QOL at Week 2 of hospitalization. Researchers chose Week 2 because studies have shown the highest symptom burden and QOL deterioration during that period.

Demographics

Patients were a mean age of 57, and a little more than half were female. Most were white, had a college degree or higher, and were married.

Their diagnoses included, for the control and intervention arms, respectively: acute lymphoblastic leukemia (9%, 5%), acute myeloid leukemia/myelodysplastic syndromes (30%, 30%), myelofibrosis/chronic myeloid leukemia (9%, 10%), lymphoma (33%, 23%), and multiple myeloma (19%, 33%).

Results

At baseline, patients in each group had comparable QOL and mood scores.

However, at Week 2, after ANCOVA adjustment for baseline scores, patients in the intervention arm had a clinically and statistically significant effect of the intervention in all areas measured except for the PHQ-9 depression score.

In particular, the HADS depression and anxiety scores were significantly improved, at P=0.008 and P<0.001, respectively, compared to control.

At 3 months, the FACT-BMT (P=0.048), HADS-Depression (P=0.002), PHQ-9-Depression (P=0.002), and  PTSD symptom (P=0.002) scores were significantly improved in the intervention group.

And at 6 months, the HADS-Depression assessment (P=0.024), the PHQ-9-Depression assessment (P=0.027), and the PTSD symptom assessment (P=0.013) remained significantly improved. However, there were no significant differences in anxiety between the 2 groups.

The researchers concluded that a relatively brief inpatient care intervention led to “remarkable sustained improvements” in depression and post-traumatic stress symptoms at 3 and 6 months after HSCT.

“This is the first study showing the benefits of palliative care for patients with hematologic malignancies undergoing stem cell transplant,” Dr El-Jawahri said.

“It’s also the first study showing the benefits of palliative care for patients with cancer pursuing curative therapy and extends the potential benefit of palliative care in a population of patients with serious illness. [T]he significant part of what palliative care does is helping patients and families cope with serious and potentially life-threatening illness.”

The researchers recommend future studies to evaluate the impact of early integration of palliative care for this patient population.

Photo courtesy of CDC

ORLANDO, FL—New research shows that patients who received inpatient palliative care while undergoing hematopoietic stem cell transplant (HSCT) experienced significant improvements in quality of life (QOL), decreases in depression, and reductions in symptom burden compared to patients who received transplant care alone.

Areej R. El-Jawahri, MD, of Harvard Medical School in Boston, Massachusetts, presented these results at the 2017 BMT Tandem Meetings (abstract 49).

She noted that palliative care is rarely used for patients with hematologic malignancies, “in part, because of misperceptions equating palliative care with just end-of-life care.”

So Dr El-Jawahri and her colleagues decided to evaluate palliative care in patients with hematologic malignancies who were scheduled to undergo HSCT.

The researchers enrolled 160 patients on the trial. Eighty-one were randomized to receive inpatient palliative care integrated with transplant care (intervention arm), and 79 were randomized to transplant care alone (control).

The latter group could request palliative care consultations, but only 2 patients did so, Dr El-Jawahri pointed out.

Patients receiving the intervention had at least twice-weekly visits with a palliative care clinician throughout their hospitalization.

“Importantly, palliative care only followed patients during their transplant hospitalization,” Dr El-Jawahri noted. “This was purely an inpatient palliative care intervention.”

Palliative care focused primarily on managing patients’ symptoms, establishing rapport with patients and families, and helping them cope with their illness. The predominant symptoms addressed included pain, nausea, diarrhea, constipation, insomnia, fatigue, depression, and anxiety.

Researchers assessed QOL, symptom burden, and mood at baseline, during hospitalization (Week 2), and at 3 and 6 months using well-validated scales.

They assessed QOL using the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) scale, mood using the Hospital Anxiety and Depression Scale (HADS) and Patient Health Questionnaire (PHQ-9), and symptom burden using the Edmonton Symptom Assessment Scale (ESAS).

They also measured post-traumatic stress (PTSD) at baseline as well as 3 and 6 months after HSCT using the PTSD checklist.

The primary endpoint of the study was patient-reported QOL at Week 2 of hospitalization. Researchers chose Week 2 because studies have shown the highest symptom burden and QOL deterioration during that period.

Demographics

Patients were a mean age of 57, and a little more than half were female. Most were white, had a college degree or higher, and were married.

Their diagnoses included, for the control and intervention arms, respectively: acute lymphoblastic leukemia (9%, 5%), acute myeloid leukemia/myelodysplastic syndromes (30%, 30%), myelofibrosis/chronic myeloid leukemia (9%, 10%), lymphoma (33%, 23%), and multiple myeloma (19%, 33%).

Results

At baseline, patients in each group had comparable QOL and mood scores.

However, at Week 2, after ANCOVA adjustment for baseline scores, patients in the intervention arm had a clinically and statistically significant effect of the intervention in all areas measured except for the PHQ-9 depression score.

In particular, the HADS depression and anxiety scores were significantly improved, at P=0.008 and P<0.001, respectively, compared to control.

At 3 months, the FACT-BMT (P=0.048), HADS-Depression (P=0.002), PHQ-9-Depression (P=0.002), and  PTSD symptom (P=0.002) scores were significantly improved in the intervention group.

And at 6 months, the HADS-Depression assessment (P=0.024), the PHQ-9-Depression assessment (P=0.027), and the PTSD symptom assessment (P=0.013) remained significantly improved. However, there were no significant differences in anxiety between the 2 groups.

The researchers concluded that a relatively brief inpatient care intervention led to “remarkable sustained improvements” in depression and post-traumatic stress symptoms at 3 and 6 months after HSCT.

“This is the first study showing the benefits of palliative care for patients with hematologic malignancies undergoing stem cell transplant,” Dr El-Jawahri said.

“It’s also the first study showing the benefits of palliative care for patients with cancer pursuing curative therapy and extends the potential benefit of palliative care in a population of patients with serious illness. [T]he significant part of what palliative care does is helping patients and families cope with serious and potentially life-threatening illness.”

The researchers recommend future studies to evaluate the impact of early integration of palliative care for this patient population.

Photo courtesy of CDC

ORLANDO, FL—New research shows that patients who received inpatient palliative care while undergoing hematopoietic stem cell transplant (HSCT) experienced significant improvements in quality of life (QOL), decreases in depression, and reductions in symptom burden compared to patients who received transplant care alone.

Areej R. El-Jawahri, MD, of Harvard Medical School in Boston, Massachusetts, presented these results at the 2017 BMT Tandem Meetings (abstract 49).

She noted that palliative care is rarely used for patients with hematologic malignancies, “in part, because of misperceptions equating palliative care with just end-of-life care.”

So Dr El-Jawahri and her colleagues decided to evaluate palliative care in patients with hematologic malignancies who were scheduled to undergo HSCT.

The researchers enrolled 160 patients on the trial. Eighty-one were randomized to receive inpatient palliative care integrated with transplant care (intervention arm), and 79 were randomized to transplant care alone (control).

The latter group could request palliative care consultations, but only 2 patients did so, Dr El-Jawahri pointed out.

Patients receiving the intervention had at least twice-weekly visits with a palliative care clinician throughout their hospitalization.

“Importantly, palliative care only followed patients during their transplant hospitalization,” Dr El-Jawahri noted. “This was purely an inpatient palliative care intervention.”

Palliative care focused primarily on managing patients’ symptoms, establishing rapport with patients and families, and helping them cope with their illness. The predominant symptoms addressed included pain, nausea, diarrhea, constipation, insomnia, fatigue, depression, and anxiety.

Researchers assessed QOL, symptom burden, and mood at baseline, during hospitalization (Week 2), and at 3 and 6 months using well-validated scales.

They assessed QOL using the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) scale, mood using the Hospital Anxiety and Depression Scale (HADS) and Patient Health Questionnaire (PHQ-9), and symptom burden using the Edmonton Symptom Assessment Scale (ESAS).

They also measured post-traumatic stress (PTSD) at baseline as well as 3 and 6 months after HSCT using the PTSD checklist.

The primary endpoint of the study was patient-reported QOL at Week 2 of hospitalization. Researchers chose Week 2 because studies have shown the highest symptom burden and QOL deterioration during that period.

Demographics

Patients were a mean age of 57, and a little more than half were female. Most were white, had a college degree or higher, and were married.

Their diagnoses included, for the control and intervention arms, respectively: acute lymphoblastic leukemia (9%, 5%), acute myeloid leukemia/myelodysplastic syndromes (30%, 30%), myelofibrosis/chronic myeloid leukemia (9%, 10%), lymphoma (33%, 23%), and multiple myeloma (19%, 33%).

Results

At baseline, patients in each group had comparable QOL and mood scores.

However, at Week 2, after ANCOVA adjustment for baseline scores, patients in the intervention arm had a clinically and statistically significant effect of the intervention in all areas measured except for the PHQ-9 depression score.

In particular, the HADS depression and anxiety scores were significantly improved, at P=0.008 and P<0.001, respectively, compared to control.

At 3 months, the FACT-BMT (P=0.048), HADS-Depression (P=0.002), PHQ-9-Depression (P=0.002), and  PTSD symptom (P=0.002) scores were significantly improved in the intervention group.

And at 6 months, the HADS-Depression assessment (P=0.024), the PHQ-9-Depression assessment (P=0.027), and the PTSD symptom assessment (P=0.013) remained significantly improved. However, there were no significant differences in anxiety between the 2 groups.

The researchers concluded that a relatively brief inpatient care intervention led to “remarkable sustained improvements” in depression and post-traumatic stress symptoms at 3 and 6 months after HSCT.

“This is the first study showing the benefits of palliative care for patients with hematologic malignancies undergoing stem cell transplant,” Dr El-Jawahri said.

“It’s also the first study showing the benefits of palliative care for patients with cancer pursuing curative therapy and extends the potential benefit of palliative care in a population of patients with serious illness. [T]he significant part of what palliative care does is helping patients and families cope with serious and potentially life-threatening illness.”

The researchers recommend future studies to evaluate the impact of early integration of palliative care for this patient population.

Photo by Rhoda Baer

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for the antiemetic agent rolapitant (Varuby) as a treatment for adults with cancer.

The drug is intended to be used in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with highly and moderately emetogenic chemotherapy.

The CHMP’s recommendation regarding rolapitant has been forwarded to the European Commission, which is expected to make a decision about the drug within 2 months.

If the commission authorizes marketing of rolapitant, the drug will be available as 90 mg film-coated tablets.

The applicant for rolapitant is Tesaro UK Limited.

Rolapitant clinical trials

Results from three phase 3 trials suggested that rolapitant (at 180 mg) in combination with a 5-HT3 receptor antagonist and dexamethasone was more effective than the 5-HT3 receptor antagonist and dexamethasone on their own (active control).

The 3-drug combination demonstrated a significant reduction in episodes of vomiting or use of rescue medication during the 25- to 120-hour period following administration of highly emetogenic and moderately emetogenic chemotherapy regimens.

In addition, patients who received rolapitant reported experiencing less nausea that interfered with normal daily life and fewer episodes of vomiting or retching over multiple cycles of chemotherapy.

Highly emetogenic chemotherapy

The clinical profile of rolapitant in cisplatin-based, highly emetogenic chemotherapy (HEC) was confirmed in two phase 3 studies: HEC1 and HEC2. Results from these trials were published in The Lancet Oncology in August 2015.

Both trials met their primary endpoint of complete response (CR) and demonstrated statistical superiority of the rolapitant combination compared to active control.

In HEC1, 264 patients received the rolapitant combination, and 262 received active control. The proportion of patients achieving a CR was 72.7% and 58.4%, respectively (P<0.001).

In HEC2, 271 patients received the rolapitant combination, and 273 received active control. The proportion of patients achieving a CR was 70.1% and 61.9%, respectively (P=0.043).

The most common adverse events (in the rolapitant and control groups, respectively) were neutropenia (9% and 8%), hiccups (5% and 4%), and abdominal pain (3% and 2%).

Moderately emetogenic chemotherapy

Researchers conducted another phase 3 trial to compare the rolapitant combination with active control in 1332 patients receiving moderately emetogenic chemotherapy. Results from this trial were also published in The Lancet Oncology in August 2015.

This trial met its primary endpoint of CR and demonstrated statistical superiority of the rolapitant combination compared to active control. The proportion of patients achieving a CR was 71.3% and 61.6%, respectively (P<0.001).

The most common adverse events (in the rolapitant and control groups, respectively) were decreased appetite (9% and 7%), neutropenia (7% and 6%), dizziness (6% and 4%), dyspepsia (4% and 2%), urinary tract infection (4% and 3%), stomatitis (4% and 2%), and anemia (3% and 2%).

Photo by Rhoda Baer

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for the antiemetic agent rolapitant (Varuby) as a treatment for adults with cancer.

The drug is intended to be used in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with highly and moderately emetogenic chemotherapy.

The CHMP’s recommendation regarding rolapitant has been forwarded to the European Commission, which is expected to make a decision about the drug within 2 months.

If the commission authorizes marketing of rolapitant, the drug will be available as 90 mg film-coated tablets.

The applicant for rolapitant is Tesaro UK Limited.

Rolapitant clinical trials

Results from three phase 3 trials suggested that rolapitant (at 180 mg) in combination with a 5-HT3 receptor antagonist and dexamethasone was more effective than the 5-HT3 receptor antagonist and dexamethasone on their own (active control).

The 3-drug combination demonstrated a significant reduction in episodes of vomiting or use of rescue medication during the 25- to 120-hour period following administration of highly emetogenic and moderately emetogenic chemotherapy regimens.

In addition, patients who received rolapitant reported experiencing less nausea that interfered with normal daily life and fewer episodes of vomiting or retching over multiple cycles of chemotherapy.

Highly emetogenic chemotherapy

The clinical profile of rolapitant in cisplatin-based, highly emetogenic chemotherapy (HEC) was confirmed in two phase 3 studies: HEC1 and HEC2. Results from these trials were published in The Lancet Oncology in August 2015.

Both trials met their primary endpoint of complete response (CR) and demonstrated statistical superiority of the rolapitant combination compared to active control.

In HEC1, 264 patients received the rolapitant combination, and 262 received active control. The proportion of patients achieving a CR was 72.7% and 58.4%, respectively (P<0.001).

In HEC2, 271 patients received the rolapitant combination, and 273 received active control. The proportion of patients achieving a CR was 70.1% and 61.9%, respectively (P=0.043).

The most common adverse events (in the rolapitant and control groups, respectively) were neutropenia (9% and 8%), hiccups (5% and 4%), and abdominal pain (3% and 2%).

Moderately emetogenic chemotherapy

Researchers conducted another phase 3 trial to compare the rolapitant combination with active control in 1332 patients receiving moderately emetogenic chemotherapy. Results from this trial were also published in The Lancet Oncology in August 2015.

This trial met its primary endpoint of CR and demonstrated statistical superiority of the rolapitant combination compared to active control. The proportion of patients achieving a CR was 71.3% and 61.6%, respectively (P<0.001).

The most common adverse events (in the rolapitant and control groups, respectively) were decreased appetite (9% and 7%), neutropenia (7% and 6%), dizziness (6% and 4%), dyspepsia (4% and 2%), urinary tract infection (4% and 3%), stomatitis (4% and 2%), and anemia (3% and 2%).

Photo by Rhoda Baer

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for the antiemetic agent rolapitant (Varuby) as a treatment for adults with cancer.

The drug is intended to be used in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with highly and moderately emetogenic chemotherapy.

The CHMP’s recommendation regarding rolapitant has been forwarded to the European Commission, which is expected to make a decision about the drug within 2 months.

If the commission authorizes marketing of rolapitant, the drug will be available as 90 mg film-coated tablets.

The applicant for rolapitant is Tesaro UK Limited.

Rolapitant clinical trials

Results from three phase 3 trials suggested that rolapitant (at 180 mg) in combination with a 5-HT3 receptor antagonist and dexamethasone was more effective than the 5-HT3 receptor antagonist and dexamethasone on their own (active control).

The 3-drug combination demonstrated a significant reduction in episodes of vomiting or use of rescue medication during the 25- to 120-hour period following administration of highly emetogenic and moderately emetogenic chemotherapy regimens.

In addition, patients who received rolapitant reported experiencing less nausea that interfered with normal daily life and fewer episodes of vomiting or retching over multiple cycles of chemotherapy.

Highly emetogenic chemotherapy

The clinical profile of rolapitant in cisplatin-based, highly emetogenic chemotherapy (HEC) was confirmed in two phase 3 studies: HEC1 and HEC2. Results from these trials were published in The Lancet Oncology in August 2015.

Both trials met their primary endpoint of complete response (CR) and demonstrated statistical superiority of the rolapitant combination compared to active control.

In HEC1, 264 patients received the rolapitant combination, and 262 received active control. The proportion of patients achieving a CR was 72.7% and 58.4%, respectively (P<0.001).

In HEC2, 271 patients received the rolapitant combination, and 273 received active control. The proportion of patients achieving a CR was 70.1% and 61.9%, respectively (P=0.043).

The most common adverse events (in the rolapitant and control groups, respectively) were neutropenia (9% and 8%), hiccups (5% and 4%), and abdominal pain (3% and 2%).

Moderately emetogenic chemotherapy

Researchers conducted another phase 3 trial to compare the rolapitant combination with active control in 1332 patients receiving moderately emetogenic chemotherapy. Results from this trial were also published in The Lancet Oncology in August 2015.

This trial met its primary endpoint of CR and demonstrated statistical superiority of the rolapitant combination compared to active control. The proportion of patients achieving a CR was 71.3% and 61.6%, respectively (P<0.001).

The most common adverse events (in the rolapitant and control groups, respectively) were decreased appetite (9% and 7%), neutropenia (7% and 6%), dizziness (6% and 4%), dyspepsia (4% and 2%), urinary tract infection (4% and 3%), stomatitis (4% and 2%), and anemia (3% and 2%).

ORLANDO – Performing a comprehensive geriatric assessment of patients with acute myeloid leukemia (AML) does more than provide fine-tuned risk stratification; spotting areas of vulnerability and frailty can also identify targets for prehabilitation, support, and remediation as older patients face transplant.

A program at the University of Chicago termed the Transplant Optimization Program, or TOP, uses the geriatric assessment as the foundation of an interdisciplinary, customized intervention for older adults facing hematopoietic cell transplant (HCT). The team includes the transplant physician and a geriatric oncologist; however, social work, dietetics, psychology, and physical therapy professionals also are brought on board.

Courtesy University of Chicago Medicine

“High comorbidities and functional limitations influence overall survival,” Dr. Artz said. “Non-relapse mortality remains a major barrier; of course, the attendant morbidity before it is perhaps a bigger concern, and our patients’ concern.”

Dr. Artz said that he and his colleagues at the University of Chicago, where he is a professor of medicine, had adapted the geriatric assessment developed by the Cancer and Aging Group, and now administer it to all prospective transplant patients aged 50 years and older. Dr. Artz said that, at his center, they have found that 25% of patients aged 50 and older were frail according to the Fried Frailty Index. “That’s what we expect for people in the community who are aged 80 and older, so we’re painting a picture of accelerated aging for patients before they undergo allograft,” he said.

Results of the assessment are then reviewed by a multidisciplinary team, and an individualized prehabilitation and support program is developed based on those results. “Using chronologic and physiologic age in transplant can help us better risk stratify, and think about strategies to mitigate some of those risks,” Dr. Artz said.

The staging tool currently used at the University of Chicago examines seven domains and uses objective tools to deliver information in each domain. Comorbidities are assessed by the Hematopoietic Cell Transplant–Specific Comorbidity Index (HCT-CI) and the Older Americans Resources and Services (OARS) scale. “We are trying to use standardized tools such as the geriatric assessment, because our ‘eyeball test’ is quite poor,” he said.

Physical function is assessed by measuring four-meter walk speed and grip strength; by asking about falls and capacity for instrumental activities of daily living; and by administering the Karnofsky Performance Scale–MD. Patients are given the Mental Health Inventory–17 to assess psychological health.

Neurocognitive testing and the Blessed Orientation-Memory-Concentration test are used to assess cognitive function. The Medical Outcomes Study Social Activity and Social Limitations scales give an idea about social support.

Biomarkers that are tracked include C-reactive protein and ferritin, among others, Dr. Artz said. Nutritional status is assessed by measuring serum albumin as well as any weight loss.

Once the full geriatric assessment data about a patient are gathered, a plan is formulated for impairments in any given domain. For example, if significant comorbid conditions exist, the TOP team seeks subspecialty consultation for management advice in the context of transplant. “This is a consultation – not a clearance!” Dr. Artz said.

Physical and functional impairments are addressed with prehabilitation if time permits, and the home assessment is aligned with patient expectations. Sometimes, the inactivity associated with peritransplant period can worsen conditions such as osteoarthritis, so a patient who’s been functional may find themselves very stiff when going home. Caregivers can encourage early activity to help minimize this effect, Dr. Artz said.

For patients at nutritional risk, it’s vital to have a good nutrition plan for transplant and to make sure medications or social factors aren’t standing in the way of adequate nutrition, Dr. Artz said. “Don’t forget to ask about dentures,” he said, since mucositis can make dentures unbearable in the immediate posttransplant period.

It’s important to be careful when unpacking findings of cognitive impairment, Dr. Artz said, since untreated depression and anxiety can manifest as forgetfulness and perseveration. Eliminating unnecessary medication, having a good delirium protocol in place, and keeping a family member in the room with the patient can help minimize a cognitive downturn during transplant.

As patients age, it can be more common for them to have limited social support. The TOP team calls a family meeting to assess resources and appoint a “team captain” among the patient’s social circle. “We work to enlarge that circle,” by pulling in as many family members and friends as possible, Dr. Artz said. In a discussion after the talk, he said that he feels that having a family member in the hospital with the older transplant patient is important for many reasons. Not only is the patient less likely to fall, he or she may also eat better and feel better. In addition, he said he has a sense that when the caregiver has seen the patient at his or her nadir, taking that patient home isn’t as scary, since it’s easier to see that the trajectory is headed upward by the time of discharge.

Dr. Artz said that other facilities are now beginning to send patients for TOP evaluations; “the aging evaluation informs physiologic age, candidacy for transplant, and may permit optimizing outcomes,” he said. “We’re trying to ... optimize patients both before and after transplant. It’s one thing to say you’re vulnerable, but how do you take that vulnerable patient and improve their outcomes? That’s the question.” Though the proportion of older individuals receiving allogeneic transplants is growing rapidly, research is not keeping up, Dr. Artz said, calling for more prospective studies in older adults.

Dr. Artz reported that he has received research funding from Miltenyi Biotech.

[email protected]
On Twitter @karioakes

ORLANDO – Performing a comprehensive geriatric assessment of patients with acute myeloid leukemia (AML) does more than provide fine-tuned risk stratification; spotting areas of vulnerability and frailty can also identify targets for prehabilitation, support, and remediation as older patients face transplant.

A program at the University of Chicago termed the Transplant Optimization Program, or TOP, uses the geriatric assessment as the foundation of an interdisciplinary, customized intervention for older adults facing hematopoietic cell transplant (HCT). The team includes the transplant physician and a geriatric oncologist; however, social work, dietetics, psychology, and physical therapy professionals also are brought on board.

Courtesy University of Chicago Medicine

“High comorbidities and functional limitations influence overall survival,” Dr. Artz said. “Non-relapse mortality remains a major barrier; of course, the attendant morbidity before it is perhaps a bigger concern, and our patients’ concern.”

Dr. Artz said that he and his colleagues at the University of Chicago, where he is a professor of medicine, had adapted the geriatric assessment developed by the Cancer and Aging Group, and now administer it to all prospective transplant patients aged 50 years and older. Dr. Artz said that, at his center, they have found that 25% of patients aged 50 and older were frail according to the Fried Frailty Index. “That’s what we expect for people in the community who are aged 80 and older, so we’re painting a picture of accelerated aging for patients before they undergo allograft,” he said.

Results of the assessment are then reviewed by a multidisciplinary team, and an individualized prehabilitation and support program is developed based on those results. “Using chronologic and physiologic age in transplant can help us better risk stratify, and think about strategies to mitigate some of those risks,” Dr. Artz said.

The staging tool currently used at the University of Chicago examines seven domains and uses objective tools to deliver information in each domain. Comorbidities are assessed by the Hematopoietic Cell Transplant–Specific Comorbidity Index (HCT-CI) and the Older Americans Resources and Services (OARS) scale. “We are trying to use standardized tools such as the geriatric assessment, because our ‘eyeball test’ is quite poor,” he said.

Physical function is assessed by measuring four-meter walk speed and grip strength; by asking about falls and capacity for instrumental activities of daily living; and by administering the Karnofsky Performance Scale–MD. Patients are given the Mental Health Inventory–17 to assess psychological health.

Neurocognitive testing and the Blessed Orientation-Memory-Concentration test are used to assess cognitive function. The Medical Outcomes Study Social Activity and Social Limitations scales give an idea about social support.

Biomarkers that are tracked include C-reactive protein and ferritin, among others, Dr. Artz said. Nutritional status is assessed by measuring serum albumin as well as any weight loss.

Once the full geriatric assessment data about a patient are gathered, a plan is formulated for impairments in any given domain. For example, if significant comorbid conditions exist, the TOP team seeks subspecialty consultation for management advice in the context of transplant. “This is a consultation – not a clearance!” Dr. Artz said.

Physical and functional impairments are addressed with prehabilitation if time permits, and the home assessment is aligned with patient expectations. Sometimes, the inactivity associated with peritransplant period can worsen conditions such as osteoarthritis, so a patient who’s been functional may find themselves very stiff when going home. Caregivers can encourage early activity to help minimize this effect, Dr. Artz said.

For patients at nutritional risk, it’s vital to have a good nutrition plan for transplant and to make sure medications or social factors aren’t standing in the way of adequate nutrition, Dr. Artz said. “Don’t forget to ask about dentures,” he said, since mucositis can make dentures unbearable in the immediate posttransplant period.

It’s important to be careful when unpacking findings of cognitive impairment, Dr. Artz said, since untreated depression and anxiety can manifest as forgetfulness and perseveration. Eliminating unnecessary medication, having a good delirium protocol in place, and keeping a family member in the room with the patient can help minimize a cognitive downturn during transplant.

As patients age, it can be more common for them to have limited social support. The TOP team calls a family meeting to assess resources and appoint a “team captain” among the patient’s social circle. “We work to enlarge that circle,” by pulling in as many family members and friends as possible, Dr. Artz said. In a discussion after the talk, he said that he feels that having a family member in the hospital with the older transplant patient is important for many reasons. Not only is the patient less likely to fall, he or she may also eat better and feel better. In addition, he said he has a sense that when the caregiver has seen the patient at his or her nadir, taking that patient home isn’t as scary, since it’s easier to see that the trajectory is headed upward by the time of discharge.

Dr. Artz said that other facilities are now beginning to send patients for TOP evaluations; “the aging evaluation informs physiologic age, candidacy for transplant, and may permit optimizing outcomes,” he said. “We’re trying to ... optimize patients both before and after transplant. It’s one thing to say you’re vulnerable, but how do you take that vulnerable patient and improve their outcomes? That’s the question.” Though the proportion of older individuals receiving allogeneic transplants is growing rapidly, research is not keeping up, Dr. Artz said, calling for more prospective studies in older adults.

Dr. Artz reported that he has received research funding from Miltenyi Biotech.

[email protected]
On Twitter @karioakes

ORLANDO – Performing a comprehensive geriatric assessment of patients with acute myeloid leukemia (AML) does more than provide fine-tuned risk stratification; spotting areas of vulnerability and frailty can also identify targets for prehabilitation, support, and remediation as older patients face transplant.

A program at the University of Chicago termed the Transplant Optimization Program, or TOP, uses the geriatric assessment as the foundation of an interdisciplinary, customized intervention for older adults facing hematopoietic cell transplant (HCT). The team includes the transplant physician and a geriatric oncologist; however, social work, dietetics, psychology, and physical therapy professionals also are brought on board.

Courtesy University of Chicago Medicine

“High comorbidities and functional limitations influence overall survival,” Dr. Artz said. “Non-relapse mortality remains a major barrier; of course, the attendant morbidity before it is perhaps a bigger concern, and our patients’ concern.”

Dr. Artz said that he and his colleagues at the University of Chicago, where he is a professor of medicine, had adapted the geriatric assessment developed by the Cancer and Aging Group, and now administer it to all prospective transplant patients aged 50 years and older. Dr. Artz said that, at his center, they have found that 25% of patients aged 50 and older were frail according to the Fried Frailty Index. “That’s what we expect for people in the community who are aged 80 and older, so we’re painting a picture of accelerated aging for patients before they undergo allograft,” he said.

Results of the assessment are then reviewed by a multidisciplinary team, and an individualized prehabilitation and support program is developed based on those results. “Using chronologic and physiologic age in transplant can help us better risk stratify, and think about strategies to mitigate some of those risks,” Dr. Artz said.

The staging tool currently used at the University of Chicago examines seven domains and uses objective tools to deliver information in each domain. Comorbidities are assessed by the Hematopoietic Cell Transplant–Specific Comorbidity Index (HCT-CI) and the Older Americans Resources and Services (OARS) scale. “We are trying to use standardized tools such as the geriatric assessment, because our ‘eyeball test’ is quite poor,” he said.

Physical function is assessed by measuring four-meter walk speed and grip strength; by asking about falls and capacity for instrumental activities of daily living; and by administering the Karnofsky Performance Scale–MD. Patients are given the Mental Health Inventory–17 to assess psychological health.

Neurocognitive testing and the Blessed Orientation-Memory-Concentration test are used to assess cognitive function. The Medical Outcomes Study Social Activity and Social Limitations scales give an idea about social support.

Biomarkers that are tracked include C-reactive protein and ferritin, among others, Dr. Artz said. Nutritional status is assessed by measuring serum albumin as well as any weight loss.

Once the full geriatric assessment data about a patient are gathered, a plan is formulated for impairments in any given domain. For example, if significant comorbid conditions exist, the TOP team seeks subspecialty consultation for management advice in the context of transplant. “This is a consultation – not a clearance!” Dr. Artz said.

Physical and functional impairments are addressed with prehabilitation if time permits, and the home assessment is aligned with patient expectations. Sometimes, the inactivity associated with peritransplant period can worsen conditions such as osteoarthritis, so a patient who’s been functional may find themselves very stiff when going home. Caregivers can encourage early activity to help minimize this effect, Dr. Artz said.

For patients at nutritional risk, it’s vital to have a good nutrition plan for transplant and to make sure medications or social factors aren’t standing in the way of adequate nutrition, Dr. Artz said. “Don’t forget to ask about dentures,” he said, since mucositis can make dentures unbearable in the immediate posttransplant period.

It’s important to be careful when unpacking findings of cognitive impairment, Dr. Artz said, since untreated depression and anxiety can manifest as forgetfulness and perseveration. Eliminating unnecessary medication, having a good delirium protocol in place, and keeping a family member in the room with the patient can help minimize a cognitive downturn during transplant.

As patients age, it can be more common for them to have limited social support. The TOP team calls a family meeting to assess resources and appoint a “team captain” among the patient’s social circle. “We work to enlarge that circle,” by pulling in as many family members and friends as possible, Dr. Artz said. In a discussion after the talk, he said that he feels that having a family member in the hospital with the older transplant patient is important for many reasons. Not only is the patient less likely to fall, he or she may also eat better and feel better. In addition, he said he has a sense that when the caregiver has seen the patient at his or her nadir, taking that patient home isn’t as scary, since it’s easier to see that the trajectory is headed upward by the time of discharge.

Dr. Artz said that other facilities are now beginning to send patients for TOP evaluations; “the aging evaluation informs physiologic age, candidacy for transplant, and may permit optimizing outcomes,” he said. “We’re trying to ... optimize patients both before and after transplant. It’s one thing to say you’re vulnerable, but how do you take that vulnerable patient and improve their outcomes? That’s the question.” Though the proportion of older individuals receiving allogeneic transplants is growing rapidly, research is not keeping up, Dr. Artz said, calling for more prospective studies in older adults.

Dr. Artz reported that he has received research funding from Miltenyi Biotech.

[email protected]
On Twitter @karioakes

Bone marrow aspirate Photo by Chad McNeeley

Two physician groups have published an evidence-based guideline that addresses the initial workup of acute leukemia.

The guideline includes 27 recommendations intended to aid treating physicians and pathologists involved in the diagnostic and prognostic evaluation of acute leukemia samples, including those from patients with acute lymphoblastic leukemia, acute myeloid leukemia, and acute leukemias of ambiguous lineage.

The guideline, which was developed through a collaboration between the College of American Pathologists (CAP) and the American Society of Hematology (ASH), has been published in the Archives of Pathology and Laboratory Medicine.

The recommendations in the guideline will also be available in a pocket guide and via the ASH Pocket Guides app in March.

“With its multidisciplinary perspective, this guideline reflects contemporary, integrated cancer care, and, therefore, it will also help providers realize efficiencies in test management,” said ASH guideline co-chair James W. Vardiman, MD, of the University of Chicago in Illinois.

To create this guideline, Dr Vardiman and his colleagues sought and reviewed relevant published evidence.

The group set out to answer 6 questions for the initial diagnosis of acute leukemias:

1) What clinical and laboratory information should be available?

2) What samples and specimen types should be evaluated?

3) What tests are required for all patients during the initial evaluation?

4) What tests are required for only a subset of patients?

5) Where should laboratory testing be performed?

6) How should the results be reported?

The authors say the guideline’s 27 recommendations answer these questions, providing a framework for the steps involved in the evaluation of acute leukemia samples.

In particular, the guideline includes steps to coordinate and communicate across clinical teams, specifying information that must be shared—particularly among treating physicians and pathologists—for optimal patient outcomes and to avoid duplicative testing.

“The laboratory testing to diagnose acute leukemia and inform treatment is increasingly complex, making this guideline essential,” said CAP guideline co-chair Daniel A. Arber, MD, of the University of Chicago.

“New gene mutations and protein expressions have been described over the last decade in all types of acute leukemia, and many of them impact diagnosis or inform prognosis.”

Bone marrow aspirate Photo by Chad McNeeley

Two physician groups have published an evidence-based guideline that addresses the initial workup of acute leukemia.

The guideline includes 27 recommendations intended to aid treating physicians and pathologists involved in the diagnostic and prognostic evaluation of acute leukemia samples, including those from patients with acute lymphoblastic leukemia, acute myeloid leukemia, and acute leukemias of ambiguous lineage.

The guideline, which was developed through a collaboration between the College of American Pathologists (CAP) and the American Society of Hematology (ASH), has been published in the Archives of Pathology and Laboratory Medicine.

The recommendations in the guideline will also be available in a pocket guide and via the ASH Pocket Guides app in March.

“With its multidisciplinary perspective, this guideline reflects contemporary, integrated cancer care, and, therefore, it will also help providers realize efficiencies in test management,” said ASH guideline co-chair James W. Vardiman, MD, of the University of Chicago in Illinois.

To create this guideline, Dr Vardiman and his colleagues sought and reviewed relevant published evidence.

The group set out to answer 6 questions for the initial diagnosis of acute leukemias:

1) What clinical and laboratory information should be available?

2) What samples and specimen types should be evaluated?

3) What tests are required for all patients during the initial evaluation?

4) What tests are required for only a subset of patients?

5) Where should laboratory testing be performed?

6) How should the results be reported?

The authors say the guideline’s 27 recommendations answer these questions, providing a framework for the steps involved in the evaluation of acute leukemia samples.

In particular, the guideline includes steps to coordinate and communicate across clinical teams, specifying information that must be shared—particularly among treating physicians and pathologists—for optimal patient outcomes and to avoid duplicative testing.

“The laboratory testing to diagnose acute leukemia and inform treatment is increasingly complex, making this guideline essential,” said CAP guideline co-chair Daniel A. Arber, MD, of the University of Chicago.

“New gene mutations and protein expressions have been described over the last decade in all types of acute leukemia, and many of them impact diagnosis or inform prognosis.”

Bone marrow aspirate Photo by Chad McNeeley

Two physician groups have published an evidence-based guideline that addresses the initial workup of acute leukemia.

The guideline includes 27 recommendations intended to aid treating physicians and pathologists involved in the diagnostic and prognostic evaluation of acute leukemia samples, including those from patients with acute lymphoblastic leukemia, acute myeloid leukemia, and acute leukemias of ambiguous lineage.

The guideline, which was developed through a collaboration between the College of American Pathologists (CAP) and the American Society of Hematology (ASH), has been published in the Archives of Pathology and Laboratory Medicine.

The recommendations in the guideline will also be available in a pocket guide and via the ASH Pocket Guides app in March.

“With its multidisciplinary perspective, this guideline reflects contemporary, integrated cancer care, and, therefore, it will also help providers realize efficiencies in test management,” said ASH guideline co-chair James W. Vardiman, MD, of the University of Chicago in Illinois.

To create this guideline, Dr Vardiman and his colleagues sought and reviewed relevant published evidence.

The group set out to answer 6 questions for the initial diagnosis of acute leukemias:

1) What clinical and laboratory information should be available?

2) What samples and specimen types should be evaluated?

3) What tests are required for all patients during the initial evaluation?

4) What tests are required for only a subset of patients?

5) Where should laboratory testing be performed?

6) How should the results be reported?

The authors say the guideline’s 27 recommendations answer these questions, providing a framework for the steps involved in the evaluation of acute leukemia samples.

In particular, the guideline includes steps to coordinate and communicate across clinical teams, specifying information that must be shared—particularly among treating physicians and pathologists—for optimal patient outcomes and to avoid duplicative testing.

“The laboratory testing to diagnose acute leukemia and inform treatment is increasingly complex, making this guideline essential,” said CAP guideline co-chair Daniel A. Arber, MD, of the University of Chicago.

“New gene mutations and protein expressions have been described over the last decade in all types of acute leukemia, and many of them impact diagnosis or inform prognosis.”

Follicular lymphoma

The European Commission has approved a biosimilar rituximab product, Truxima™, for all the same indications as the reference product, MabThera.

This means Truxima (formerly called CT-P10) is approved for use in the European Union to treat patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA).

Truxima, a product of Celltrion Healthcare Hungary Kft, is the first biosimilar monoclonal antibody approved in an oncology indication worldwide.

The approval is based on data submitted to the European Medicines Agency.

The agency’s Committee for Medicinal Products for Human Use (CHMP) said the evidence suggests Truxima and MabThera are similar in terms of efficacy, safety, immunogenicity, pharmacodynamics, and pharmacokinetics in patients with RA and advanced follicular lymphoma (FL).

Therefore, the European Commission approved Truxima for the following indications.

Non-Hodgkin lymphoma 

Truxima is indicated for use in combination with chemotherapy to treat previously untreated patients with stage III-IV FL.

Truxima maintenance therapy is indicated for the treatment of FL patients responding to induction therapy.

Truxima monotherapy is indicated for the treatment of patients with stage III-IV FL who are chemo-resistant or are in their second or subsequent relapse after chemotherapy.

Truxima is indicated for use in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) for the treatment of patients with CD20-positive diffuse large B-cell lymphoma.

Chronic lymphocytic leukemia

Truxima in combination with chemotherapy is indicated for the treatment of patients with previously untreated and relapsed/refractory chronic lymphocytic leukemia.

The CHMP noted that limited efficacy and safety data are available for patients previously treated with monoclonal antibodies, including rituximab, or patients who are refractory to previous rituximab plus chemotherapy.

RA, GPA, and MPA 

Truxima in combination with methotrexate is indicated for the treatment of adults with severe, active RA who have had an inadequate response to or cannot tolerate other disease-modifying anti-rheumatic drugs, including one or more tumor necrosis factor inhibitor therapies.

Truxima in combination with glucocorticoids is indicated for the induction of remission in adults with severe, active GPA or MPA.

Truxima studies

There are 3 ongoing, phase 3 trials of Truxima in patients with RA (NCT02149121), advanced FL (NCT02162771), and low-tumor-burden FL (NCT02260804).

Results from the phase 1/3 trial in patients with newly diagnosed, advanced FL suggest that Truxima and the reference rituximab are similar with regard to pharmacokinetics, immunogenicity, and safety (B Coiffier et al. ASH 2016, abstract 1807).

Results from the phase 3 study of RA patients indicate that Truxima is similar to reference products (EU and US-sourced rituximab) with regard to pharmacodynamics, safety, and efficacy for up to 24 weeks (DH Yoo et al. 2016 ACR/ARHP Annual Meeting, abstract 1635).  

Follicular lymphoma

The European Commission has approved a biosimilar rituximab product, Truxima™, for all the same indications as the reference product, MabThera.

This means Truxima (formerly called CT-P10) is approved for use in the European Union to treat patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA).

Truxima, a product of Celltrion Healthcare Hungary Kft, is the first biosimilar monoclonal antibody approved in an oncology indication worldwide.

The approval is based on data submitted to the European Medicines Agency.

The agency’s Committee for Medicinal Products for Human Use (CHMP) said the evidence suggests Truxima and MabThera are similar in terms of efficacy, safety, immunogenicity, pharmacodynamics, and pharmacokinetics in patients with RA and advanced follicular lymphoma (FL).

Therefore, the European Commission approved Truxima for the following indications.

Non-Hodgkin lymphoma 

Truxima is indicated for use in combination with chemotherapy to treat previously untreated patients with stage III-IV FL.

Truxima maintenance therapy is indicated for the treatment of FL patients responding to induction therapy.

Truxima monotherapy is indicated for the treatment of patients with stage III-IV FL who are chemo-resistant or are in their second or subsequent relapse after chemotherapy.

Truxima is indicated for use in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) for the treatment of patients with CD20-positive diffuse large B-cell lymphoma.

Chronic lymphocytic leukemia

Truxima in combination with chemotherapy is indicated for the treatment of patients with previously untreated and relapsed/refractory chronic lymphocytic leukemia.

The CHMP noted that limited efficacy and safety data are available for patients previously treated with monoclonal antibodies, including rituximab, or patients who are refractory to previous rituximab plus chemotherapy.

RA, GPA, and MPA 

Truxima in combination with methotrexate is indicated for the treatment of adults with severe, active RA who have had an inadequate response to or cannot tolerate other disease-modifying anti-rheumatic drugs, including one or more tumor necrosis factor inhibitor therapies.

Truxima in combination with glucocorticoids is indicated for the induction of remission in adults with severe, active GPA or MPA.

Truxima studies

There are 3 ongoing, phase 3 trials of Truxima in patients with RA (NCT02149121), advanced FL (NCT02162771), and low-tumor-burden FL (NCT02260804).

Results from the phase 1/3 trial in patients with newly diagnosed, advanced FL suggest that Truxima and the reference rituximab are similar with regard to pharmacokinetics, immunogenicity, and safety (B Coiffier et al. ASH 2016, abstract 1807).

Results from the phase 3 study of RA patients indicate that Truxima is similar to reference products (EU and US-sourced rituximab) with regard to pharmacodynamics, safety, and efficacy for up to 24 weeks (DH Yoo et al. 2016 ACR/ARHP Annual Meeting, abstract 1635).  

Follicular lymphoma

The European Commission has approved a biosimilar rituximab product, Truxima™, for all the same indications as the reference product, MabThera.

This means Truxima (formerly called CT-P10) is approved for use in the European Union to treat patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA).

Truxima, a product of Celltrion Healthcare Hungary Kft, is the first biosimilar monoclonal antibody approved in an oncology indication worldwide.

The approval is based on data submitted to the European Medicines Agency.

The agency’s Committee for Medicinal Products for Human Use (CHMP) said the evidence suggests Truxima and MabThera are similar in terms of efficacy, safety, immunogenicity, pharmacodynamics, and pharmacokinetics in patients with RA and advanced follicular lymphoma (FL).

Therefore, the European Commission approved Truxima for the following indications.

Non-Hodgkin lymphoma 

Truxima is indicated for use in combination with chemotherapy to treat previously untreated patients with stage III-IV FL.

Truxima maintenance therapy is indicated for the treatment of FL patients responding to induction therapy.

Truxima monotherapy is indicated for the treatment of patients with stage III-IV FL who are chemo-resistant or are in their second or subsequent relapse after chemotherapy.

Truxima is indicated for use in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) for the treatment of patients with CD20-positive diffuse large B-cell lymphoma.

Chronic lymphocytic leukemia

Truxima in combination with chemotherapy is indicated for the treatment of patients with previously untreated and relapsed/refractory chronic lymphocytic leukemia.

The CHMP noted that limited efficacy and safety data are available for patients previously treated with monoclonal antibodies, including rituximab, or patients who are refractory to previous rituximab plus chemotherapy.

RA, GPA, and MPA 

Truxima in combination with methotrexate is indicated for the treatment of adults with severe, active RA who have had an inadequate response to or cannot tolerate other disease-modifying anti-rheumatic drugs, including one or more tumor necrosis factor inhibitor therapies.

Truxima in combination with glucocorticoids is indicated for the induction of remission in adults with severe, active GPA or MPA.

Truxima studies

There are 3 ongoing, phase 3 trials of Truxima in patients with RA (NCT02149121), advanced FL (NCT02162771), and low-tumor-burden FL (NCT02260804).

Results from the phase 1/3 trial in patients with newly diagnosed, advanced FL suggest that Truxima and the reference rituximab are similar with regard to pharmacokinetics, immunogenicity, and safety (B Coiffier et al. ASH 2016, abstract 1807).

Results from the phase 3 study of RA patients indicate that Truxima is similar to reference products (EU and US-sourced rituximab) with regard to pharmacodynamics, safety, and efficacy for up to 24 weeks (DH Yoo et al. 2016 ACR/ARHP Annual Meeting, abstract 1635).  

Photo courtesy of CDC

A new analysis indicates that cancer survivors may be more likely than the rest of the US population to change their prescription drug use due to financial concerns.

The study showed that cancer survivors were more likely to delay filling prescriptions, skip medication doses, request cheaper medications from their doctors, and engage in other cost-saving behaviors.

However, this was only true for non-elderly individuals.

There was no significant difference in cost-saving behaviors between elderly (age 65 and older) cancer survivors and elderly individuals in the general population.

Ahmedin Jemal, DVM, PhD, of the American Cancer Society in Atlanta, Georgia, and his colleagues reported these findings in Cancer.

The researchers used 2011-2014 data from the National Health Interview Survey, an annual household interview survey conducted by the US Centers for Disease Control and Prevention.

The survey included 8931 cancer survivors and 126,287 individuals without a cancer history.

Among non-elderly adults, 31.6% of those who had been diagnosed with cancer recently and 27.9% of those who had been diagnosed at least 2 years earlier reported a change in prescription drug use for financial reasons, compared with 21.4% of individuals without a history of cancer (P<0.05).

“Specifically, non-elderly cancer survivors were more likely to skip medication, delay filling a prescription, ask their doctor for lower-cost medication, and use alternative therapies for financial reasons compared with non-elderly individuals without a cancer history,” Dr Jemal said.

On the other hand, changes in prescription drug use for financial reasons were generally similar between elderly cancer survivors and elderly individuals without a cancer history.

The proportion of elderly individuals who changed their drug use for financial reasons was 24.9% among those who had been diagnosed with cancer recently, 21.8% among those who had been diagnosed at least 2 years earlier, and 20.4% among those without a history of cancer.

The researchers said these results could be explained by uniform healthcare coverage through Medicare.

The team also said their findings may have significant policy implications.

“Healthcare reforms addressing the financial burden of cancer among survivors, including the escalating cost of prescription drugs, should consider multiple comorbid conditions and high-deductible health plans, and the working poor,” Dr Jemal said.

“Our findings also have implications for doctor and patient communication about the financial burden of cancer when making treatment decisions, especially on the use of certain drugs that cost hundreds of thousands of dollars but with very small benefit compared with alternative and more affordable drugs.”

Photo courtesy of CDC

A new analysis indicates that cancer survivors may be more likely than the rest of the US population to change their prescription drug use due to financial concerns.

The study showed that cancer survivors were more likely to delay filling prescriptions, skip medication doses, request cheaper medications from their doctors, and engage in other cost-saving behaviors.

However, this was only true for non-elderly individuals.

There was no significant difference in cost-saving behaviors between elderly (age 65 and older) cancer survivors and elderly individuals in the general population.

Ahmedin Jemal, DVM, PhD, of the American Cancer Society in Atlanta, Georgia, and his colleagues reported these findings in Cancer.

The researchers used 2011-2014 data from the National Health Interview Survey, an annual household interview survey conducted by the US Centers for Disease Control and Prevention.

The survey included 8931 cancer survivors and 126,287 individuals without a cancer history.

Among non-elderly adults, 31.6% of those who had been diagnosed with cancer recently and 27.9% of those who had been diagnosed at least 2 years earlier reported a change in prescription drug use for financial reasons, compared with 21.4% of individuals without a history of cancer (P<0.05).

“Specifically, non-elderly cancer survivors were more likely to skip medication, delay filling a prescription, ask their doctor for lower-cost medication, and use alternative therapies for financial reasons compared with non-elderly individuals without a cancer history,” Dr Jemal said.

On the other hand, changes in prescription drug use for financial reasons were generally similar between elderly cancer survivors and elderly individuals without a cancer history.

The proportion of elderly individuals who changed their drug use for financial reasons was 24.9% among those who had been diagnosed with cancer recently, 21.8% among those who had been diagnosed at least 2 years earlier, and 20.4% among those without a history of cancer.

The researchers said these results could be explained by uniform healthcare coverage through Medicare.

The team also said their findings may have significant policy implications.

“Healthcare reforms addressing the financial burden of cancer among survivors, including the escalating cost of prescription drugs, should consider multiple comorbid conditions and high-deductible health plans, and the working poor,” Dr Jemal said.

“Our findings also have implications for doctor and patient communication about the financial burden of cancer when making treatment decisions, especially on the use of certain drugs that cost hundreds of thousands of dollars but with very small benefit compared with alternative and more affordable drugs.”

Photo courtesy of CDC

A new analysis indicates that cancer survivors may be more likely than the rest of the US population to change their prescription drug use due to financial concerns.

The study showed that cancer survivors were more likely to delay filling prescriptions, skip medication doses, request cheaper medications from their doctors, and engage in other cost-saving behaviors.

However, this was only true for non-elderly individuals.

There was no significant difference in cost-saving behaviors between elderly (age 65 and older) cancer survivors and elderly individuals in the general population.

Ahmedin Jemal, DVM, PhD, of the American Cancer Society in Atlanta, Georgia, and his colleagues reported these findings in Cancer.

The researchers used 2011-2014 data from the National Health Interview Survey, an annual household interview survey conducted by the US Centers for Disease Control and Prevention.

The survey included 8931 cancer survivors and 126,287 individuals without a cancer history.

Among non-elderly adults, 31.6% of those who had been diagnosed with cancer recently and 27.9% of those who had been diagnosed at least 2 years earlier reported a change in prescription drug use for financial reasons, compared with 21.4% of individuals without a history of cancer (P<0.05).

“Specifically, non-elderly cancer survivors were more likely to skip medication, delay filling a prescription, ask their doctor for lower-cost medication, and use alternative therapies for financial reasons compared with non-elderly individuals without a cancer history,” Dr Jemal said.

On the other hand, changes in prescription drug use for financial reasons were generally similar between elderly cancer survivors and elderly individuals without a cancer history.

The proportion of elderly individuals who changed their drug use for financial reasons was 24.9% among those who had been diagnosed with cancer recently, 21.8% among those who had been diagnosed at least 2 years earlier, and 20.4% among those without a history of cancer.

The researchers said these results could be explained by uniform healthcare coverage through Medicare.

The team also said their findings may have significant policy implications.

“Healthcare reforms addressing the financial burden of cancer among survivors, including the escalating cost of prescription drugs, should consider multiple comorbid conditions and high-deductible health plans, and the working poor,” Dr Jemal said.

“Our findings also have implications for doctor and patient communication about the financial burden of cancer when making treatment decisions, especially on the use of certain drugs that cost hundreds of thousands of dollars but with very small benefit compared with alternative and more affordable drugs.”

B-cell precursor ALL

The US Food and Drug Administration (FDA) has granted priority review for inotuzumab ozogamicin as a treatment for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10-month period.

The Prescription Drug User Fee Act goal date for inotuzumab ozogamicin is August 2017.

About inotuzumab ozogamicin

Inotuzumab ozogamicin is an antibody-drug conjugate that consists of a monoclonal antibody targeting CD22 and a cytotoxic agent known as calicheamicin.

The product originates from a collaboration between Pfizer and Celltech (now UCB), but Pfizer has sole responsibility for all manufacturing and clinical development activities.

The application for inotuzumab ozogamicin is supported by results from a phase 3 trial, which were published in NEJM in June 2016.

The trial enrolled 326 adult patients with relapsed or refractory B-cell ALL and compared inotuzumab ozogamicin to standard of care chemotherapy.

The rate of complete remission, including incomplete hematologic recovery, was 80.7% in the inotuzumab arm and 29.4% in the chemotherapy arm (P<0.001). The median duration of remission was 4.6 months and 3.1 months, respectively (P=0.03).

Forty-one percent of patients treated with inotuzumab and 11% of those who received chemotherapy proceeded to stem cell transplant directly after treatment (P<0.001).

The median progression-free survival was 5.0 months in the inotuzumab arm and 1.8 months in the chemotherapy arm (P<0.001).

The median overall survival was 7.7 months and 6.7 months, respectively (P=0.04). This did not meet the prespecified boundary of significance (P=0.0208).

Liver-related adverse events were more common in the inotuzumab arm than the chemotherapy arm. The most frequent of these were increased aspartate aminotransferase level (20% vs 10%), hyperbilirubinemia (15% vs 10%), and increased alanine aminotransferase level (14% vs 11%).

Veno-occlusive liver disease occurred in 11% of patients in the inotuzumab arm and 1% in the chemotherapy arm.

There were 17 deaths during treatment in the inotuzumab arm and 11 in the chemotherapy arm. Four deaths were considered related to inotuzumab, and 2 were thought to be related to chemotherapy.

B-cell precursor ALL

The US Food and Drug Administration (FDA) has granted priority review for inotuzumab ozogamicin as a treatment for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10-month period.

The Prescription Drug User Fee Act goal date for inotuzumab ozogamicin is August 2017.

About inotuzumab ozogamicin

Inotuzumab ozogamicin is an antibody-drug conjugate that consists of a monoclonal antibody targeting CD22 and a cytotoxic agent known as calicheamicin.

The product originates from a collaboration between Pfizer and Celltech (now UCB), but Pfizer has sole responsibility for all manufacturing and clinical development activities.

The application for inotuzumab ozogamicin is supported by results from a phase 3 trial, which were published in NEJM in June 2016.

The trial enrolled 326 adult patients with relapsed or refractory B-cell ALL and compared inotuzumab ozogamicin to standard of care chemotherapy.

The rate of complete remission, including incomplete hematologic recovery, was 80.7% in the inotuzumab arm and 29.4% in the chemotherapy arm (P<0.001). The median duration of remission was 4.6 months and 3.1 months, respectively (P=0.03).

Forty-one percent of patients treated with inotuzumab and 11% of those who received chemotherapy proceeded to stem cell transplant directly after treatment (P<0.001).

The median progression-free survival was 5.0 months in the inotuzumab arm and 1.8 months in the chemotherapy arm (P<0.001).

The median overall survival was 7.7 months and 6.7 months, respectively (P=0.04). This did not meet the prespecified boundary of significance (P=0.0208).

Liver-related adverse events were more common in the inotuzumab arm than the chemotherapy arm. The most frequent of these were increased aspartate aminotransferase level (20% vs 10%), hyperbilirubinemia (15% vs 10%), and increased alanine aminotransferase level (14% vs 11%).

Veno-occlusive liver disease occurred in 11% of patients in the inotuzumab arm and 1% in the chemotherapy arm.

There were 17 deaths during treatment in the inotuzumab arm and 11 in the chemotherapy arm. Four deaths were considered related to inotuzumab, and 2 were thought to be related to chemotherapy.

B-cell precursor ALL

The US Food and Drug Administration (FDA) has granted priority review for inotuzumab ozogamicin as a treatment for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10-month period.

The Prescription Drug User Fee Act goal date for inotuzumab ozogamicin is August 2017.

About inotuzumab ozogamicin

Inotuzumab ozogamicin is an antibody-drug conjugate that consists of a monoclonal antibody targeting CD22 and a cytotoxic agent known as calicheamicin.

The product originates from a collaboration between Pfizer and Celltech (now UCB), but Pfizer has sole responsibility for all manufacturing and clinical development activities.

The application for inotuzumab ozogamicin is supported by results from a phase 3 trial, which were published in NEJM in June 2016.

The trial enrolled 326 adult patients with relapsed or refractory B-cell ALL and compared inotuzumab ozogamicin to standard of care chemotherapy.

The rate of complete remission, including incomplete hematologic recovery, was 80.7% in the inotuzumab arm and 29.4% in the chemotherapy arm (P<0.001). The median duration of remission was 4.6 months and 3.1 months, respectively (P=0.03).

Forty-one percent of patients treated with inotuzumab and 11% of those who received chemotherapy proceeded to stem cell transplant directly after treatment (P<0.001).

The median progression-free survival was 5.0 months in the inotuzumab arm and 1.8 months in the chemotherapy arm (P<0.001).

The median overall survival was 7.7 months and 6.7 months, respectively (P=0.04). This did not meet the prespecified boundary of significance (P=0.0208).

Liver-related adverse events were more common in the inotuzumab arm than the chemotherapy arm. The most frequent of these were increased aspartate aminotransferase level (20% vs 10%), hyperbilirubinemia (15% vs 10%), and increased alanine aminotransferase level (14% vs 11%).

Veno-occlusive liver disease occurred in 11% of patients in the inotuzumab arm and 1% in the chemotherapy arm.

There were 17 deaths during treatment in the inotuzumab arm and 11 in the chemotherapy arm. Four deaths were considered related to inotuzumab, and 2 were thought to be related to chemotherapy.