Lymphoma & Plasma Cell Disorders

The Food and Drug Administration has approved duvelisib (Copiktra), a dual PI3K delta/gamma inhibitor, for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma.

Duvelisib has full FDA approval to treat adults with relapsed or refractory CLL/SLL who have received at least two prior therapies. Duvelisib also has accelerated approval to treat adults with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.

Accelerated approval is based on a surrogate or intermediate endpoint – in this case, overall response rate – that is reasonably likely to predict clinical benefit. Continued approval of duvelisib in FL may be contingent upon results of confirmatory trials verifying that the drug provides a clinical benefit.

Duvelisib will be available in the U.S. immediately, according to Verastem, the company marketing the drug. The prescribing information for duvelisib includes a boxed warning detailing four fatal and/or serious toxicities associated with the drug – infections, diarrhea or colitis, cutaneous reactions, and pneumonitis. Verastem said it is implementing an informational risk evaluation and mitigation strategy to provide appropriate dosing and safety information for duvelisib.

The recommended dose of duvelisib is 25 mg orally twice daily, taken continuously in 28-day treatment cycles.

The FDA’s approval of duvelisib is supported by data from the phase 3 DUO trial and the phase 2 DYNAMO trial. The DUO trial included 319 patients with CLL (n=312) or SLL (n=7) who had received at least one prior therapy. They were randomized to receive either duvelisib (25 mg orally twice daily) or ofatumumab (initial infusion of 300 mg followed by 7 weekly infusions and 4 monthly infusions of 2,000 mg).

Efficacy results are based on patients who had received at least two prior therapies, including 95 patients in the duvelisib arm and 101 in the ofatumumab arm. The overall response rate was 78% in the duvelisib arm and 39% in the ofatumumab arm. All responses in both arms were partial responses.

The median progression-free survival was 16.4 months with duvelisib and 9.1 months with ofatumumab.

The safety results include all patients treated with duvelisib or ofatumumab in this trial. In the duvelisib arm, 12% of patients had fatal adverse events (AEs) within 30 days of the last dose. The same was true of 4% of patients treated with ofatumumab. Serious AEs occurred in 73% of patients treated with duvelisib. The most common were infection and diarrhea/colitis. The DYNAMO trial enrolled patients with indolent non-Hodgkin lymphoma whose disease was refractory to both rituximab and chemotherapy or radioimmunotherapy. There were 83 patients with FL.

Patients received duvelisib at 25 mg orally twice daily until disease progression or unacceptable toxicity.

The overall response rate was 42%. One patient achieved a complete response, and 34 had a partial response.

Forty-three percent of responders maintained their response at 6 months, and 17% maintained their response at 12 months.

Serious AEs occurred in 58% of FL patients. The most common were diarrhea/colitis, pneumonia, renal insufficiency, rash, and sepsis.

jensmith@mdedge.com

The Food and Drug Administration has approved duvelisib (Copiktra), a dual PI3K delta/gamma inhibitor, for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma.

Duvelisib has full FDA approval to treat adults with relapsed or refractory CLL/SLL who have received at least two prior therapies. Duvelisib also has accelerated approval to treat adults with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.

Accelerated approval is based on a surrogate or intermediate endpoint – in this case, overall response rate – that is reasonably likely to predict clinical benefit. Continued approval of duvelisib in FL may be contingent upon results of confirmatory trials verifying that the drug provides a clinical benefit.

Duvelisib will be available in the U.S. immediately, according to Verastem, the company marketing the drug. The prescribing information for duvelisib includes a boxed warning detailing four fatal and/or serious toxicities associated with the drug – infections, diarrhea or colitis, cutaneous reactions, and pneumonitis. Verastem said it is implementing an informational risk evaluation and mitigation strategy to provide appropriate dosing and safety information for duvelisib.

The recommended dose of duvelisib is 25 mg orally twice daily, taken continuously in 28-day treatment cycles.

The FDA’s approval of duvelisib is supported by data from the phase 3 DUO trial and the phase 2 DYNAMO trial. The DUO trial included 319 patients with CLL (n=312) or SLL (n=7) who had received at least one prior therapy. They were randomized to receive either duvelisib (25 mg orally twice daily) or ofatumumab (initial infusion of 300 mg followed by 7 weekly infusions and 4 monthly infusions of 2,000 mg).

Efficacy results are based on patients who had received at least two prior therapies, including 95 patients in the duvelisib arm and 101 in the ofatumumab arm. The overall response rate was 78% in the duvelisib arm and 39% in the ofatumumab arm. All responses in both arms were partial responses.

The median progression-free survival was 16.4 months with duvelisib and 9.1 months with ofatumumab.

The safety results include all patients treated with duvelisib or ofatumumab in this trial. In the duvelisib arm, 12% of patients had fatal adverse events (AEs) within 30 days of the last dose. The same was true of 4% of patients treated with ofatumumab. Serious AEs occurred in 73% of patients treated with duvelisib. The most common were infection and diarrhea/colitis. The DYNAMO trial enrolled patients with indolent non-Hodgkin lymphoma whose disease was refractory to both rituximab and chemotherapy or radioimmunotherapy. There were 83 patients with FL.

Patients received duvelisib at 25 mg orally twice daily until disease progression or unacceptable toxicity.

The overall response rate was 42%. One patient achieved a complete response, and 34 had a partial response.

Forty-three percent of responders maintained their response at 6 months, and 17% maintained their response at 12 months.

Serious AEs occurred in 58% of FL patients. The most common were diarrhea/colitis, pneumonia, renal insufficiency, rash, and sepsis.

jensmith@mdedge.com

The Food and Drug Administration has approved duvelisib (Copiktra), a dual PI3K delta/gamma inhibitor, for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma.

Duvelisib has full FDA approval to treat adults with relapsed or refractory CLL/SLL who have received at least two prior therapies. Duvelisib also has accelerated approval to treat adults with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.

Accelerated approval is based on a surrogate or intermediate endpoint – in this case, overall response rate – that is reasonably likely to predict clinical benefit. Continued approval of duvelisib in FL may be contingent upon results of confirmatory trials verifying that the drug provides a clinical benefit.

Duvelisib will be available in the U.S. immediately, according to Verastem, the company marketing the drug. The prescribing information for duvelisib includes a boxed warning detailing four fatal and/or serious toxicities associated with the drug – infections, diarrhea or colitis, cutaneous reactions, and pneumonitis. Verastem said it is implementing an informational risk evaluation and mitigation strategy to provide appropriate dosing and safety information for duvelisib.

The recommended dose of duvelisib is 25 mg orally twice daily, taken continuously in 28-day treatment cycles.

The FDA’s approval of duvelisib is supported by data from the phase 3 DUO trial and the phase 2 DYNAMO trial. The DUO trial included 319 patients with CLL (n=312) or SLL (n=7) who had received at least one prior therapy. They were randomized to receive either duvelisib (25 mg orally twice daily) or ofatumumab (initial infusion of 300 mg followed by 7 weekly infusions and 4 monthly infusions of 2,000 mg).

Efficacy results are based on patients who had received at least two prior therapies, including 95 patients in the duvelisib arm and 101 in the ofatumumab arm. The overall response rate was 78% in the duvelisib arm and 39% in the ofatumumab arm. All responses in both arms were partial responses.

The median progression-free survival was 16.4 months with duvelisib and 9.1 months with ofatumumab.

The safety results include all patients treated with duvelisib or ofatumumab in this trial. In the duvelisib arm, 12% of patients had fatal adverse events (AEs) within 30 days of the last dose. The same was true of 4% of patients treated with ofatumumab. Serious AEs occurred in 73% of patients treated with duvelisib. The most common were infection and diarrhea/colitis. The DYNAMO trial enrolled patients with indolent non-Hodgkin lymphoma whose disease was refractory to both rituximab and chemotherapy or radioimmunotherapy. There were 83 patients with FL.

Patients received duvelisib at 25 mg orally twice daily until disease progression or unacceptable toxicity.

The overall response rate was 42%. One patient achieved a complete response, and 34 had a partial response.

Forty-three percent of responders maintained their response at 6 months, and 17% maintained their response at 12 months.

Serious AEs occurred in 58% of FL patients. The most common were diarrhea/colitis, pneumonia, renal insufficiency, rash, and sepsis.

jensmith@mdedge.com

Micrograph showing CLL

The U.S. Food and Drug Administration (FDA) has approved duvelisib (Copiktra™), a dual PI3K delta/gamma inhibitor, for two indications.

Duvelisib has full FDA approval to treat adults with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have received at least two prior therapies.

Duvelisib also has accelerated approval to treat adults with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.

Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit. Continued approval of duvelisib in FL may be contingent upon results of confirmatory trials verifying that the drug provides a clinical benefit.

Duvelisib will be available in the U.S. immediately, according to Verastem Inc., the company marketing the drug.

Verastem said it will help patients access duvelisib through the Verastem Cares™ program, which is designed to provide information and assistance to patients who are prescribed duvelisib.

The prescribing information for duvelisib includes a boxed warning detailing four fatal and/or serious toxicities associated with the drug—infections, diarrhea or colitis, cutaneous reactions, and pneumonitis.

Verastem said it is implementing an informational risk evaluation and mitigation strategy to provide appropriate dosing and safety information for duvelisib.

The recommended dose of duvelisib is 25 mg orally twice daily, taken continuously in 28-day treatment cycles.

The FDA assessed the new drug application for duvelisib under priority review. The FDA also granted duvelisib fast track designation in CLL and FL as well as orphan drug designation for CLL/SLL and FL.

The FDA’s approval of duvelisib is supported by data from the phase 3 DUO trial and the phase 2 DYNAMO trial. Updated results from both studies are available in the prescribing information for duvelisib.

DUO trial

DUO included 319 patients with CLL (n=312) or SLL (n=7) who had received at least one prior therapy. They were randomized to receive either duvelisib (25 mg orally twice daily) or ofatumumab (initial infusion of 300 mg followed by 7 weekly infusions and 4 monthly infusions of 2000 mg).

The following efficacy results were observed in patients who had received at least two prior therapies, which includes 95 patients in the duvelisib arm and 101 in the ofatumumab arm.

The overall response rate was 78% in the duvelisib arm and 39% in the ofatumumab arm. All responses in both arms were partial responses.

The median progression-free survival was 16.4 months with duvelisib and 9.1 months with ofatumumab (hazard ratio=0.40).

The safety results include all patients treated with duvelisib or ofatumumab.

Twelve percent of patients in the duvelisib arm had fatal adverse events (AEs) within 30 days of the last dose. The same was true of 4% of patients treated with ofatumumab.

Serious AEs occurred in 73% of patients treated with duvelisib. The most common were infection (38%) and diarrhea/colitis (23%).

Thirty-six percent of patients discontinued duvelisib. Most discontinuations were due to diarrhea/ colitis, infection, and rash. Twenty-nine percent of patients in the duvelisib arm required dose reductions, most often due to diarrhea/colitis and rash.

DYNAMO trial

DYNAMO enrolled patients with indolent non-Hodgkin lymphoma whose disease was refractory to both rituximab and chemotherapy or radioimmunotherapy.

There were 83 patients with FL. They had a median of 3 prior anticancer regimens (range, 1-10).

The patients received duvelisib at 25 mg orally twice daily until disease progression or unacceptable toxicity.

The overall response rate was 42%. One patient achieved a complete response, and 34 had a partial response.

Forty-three percent of responders maintained their response at 6 months, and 17% maintained their response at 12 months.

Serious AEs occurred in 58% of FL patients. The most common were diarrhea/colitis, pneumonia, renal insufficiency, rash, and sepsis.

AEs occurring in at least 20% of FL patients included diarrhea/colitis, nausea, fatigue, musculoskeletal pain, rash, neutropenia, cough, anemia, pyrexia, headache, mucositis, abdominal pain, vomiting, transaminase elevation, and thrombocytopenia.

Twenty-nine percent of FL patients discontinued duvelisib, and 23% had dose reductions. Most discontinuations were due to diarrhea/colitis and rash, and most dose reductions were due to transaminase elevation, diarrhea/colitis, lipase increase, and infection.

Micrograph showing CLL

The U.S. Food and Drug Administration (FDA) has approved duvelisib (Copiktra™), a dual PI3K delta/gamma inhibitor, for two indications.

Duvelisib has full FDA approval to treat adults with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have received at least two prior therapies.

Duvelisib also has accelerated approval to treat adults with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.

Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit. Continued approval of duvelisib in FL may be contingent upon results of confirmatory trials verifying that the drug provides a clinical benefit.

Duvelisib will be available in the U.S. immediately, according to Verastem Inc., the company marketing the drug.

Verastem said it will help patients access duvelisib through the Verastem Cares™ program, which is designed to provide information and assistance to patients who are prescribed duvelisib.

The prescribing information for duvelisib includes a boxed warning detailing four fatal and/or serious toxicities associated with the drug—infections, diarrhea or colitis, cutaneous reactions, and pneumonitis.

Verastem said it is implementing an informational risk evaluation and mitigation strategy to provide appropriate dosing and safety information for duvelisib.

The recommended dose of duvelisib is 25 mg orally twice daily, taken continuously in 28-day treatment cycles.

The FDA assessed the new drug application for duvelisib under priority review. The FDA also granted duvelisib fast track designation in CLL and FL as well as orphan drug designation for CLL/SLL and FL.

The FDA’s approval of duvelisib is supported by data from the phase 3 DUO trial and the phase 2 DYNAMO trial. Updated results from both studies are available in the prescribing information for duvelisib.

DUO trial

DUO included 319 patients with CLL (n=312) or SLL (n=7) who had received at least one prior therapy. They were randomized to receive either duvelisib (25 mg orally twice daily) or ofatumumab (initial infusion of 300 mg followed by 7 weekly infusions and 4 monthly infusions of 2000 mg).

The following efficacy results were observed in patients who had received at least two prior therapies, which includes 95 patients in the duvelisib arm and 101 in the ofatumumab arm.

The overall response rate was 78% in the duvelisib arm and 39% in the ofatumumab arm. All responses in both arms were partial responses.

The median progression-free survival was 16.4 months with duvelisib and 9.1 months with ofatumumab (hazard ratio=0.40).

The safety results include all patients treated with duvelisib or ofatumumab.

Twelve percent of patients in the duvelisib arm had fatal adverse events (AEs) within 30 days of the last dose. The same was true of 4% of patients treated with ofatumumab.

Serious AEs occurred in 73% of patients treated with duvelisib. The most common were infection (38%) and diarrhea/colitis (23%).

Thirty-six percent of patients discontinued duvelisib. Most discontinuations were due to diarrhea/ colitis, infection, and rash. Twenty-nine percent of patients in the duvelisib arm required dose reductions, most often due to diarrhea/colitis and rash.

DYNAMO trial

DYNAMO enrolled patients with indolent non-Hodgkin lymphoma whose disease was refractory to both rituximab and chemotherapy or radioimmunotherapy.

There were 83 patients with FL. They had a median of 3 prior anticancer regimens (range, 1-10).

The patients received duvelisib at 25 mg orally twice daily until disease progression or unacceptable toxicity.

The overall response rate was 42%. One patient achieved a complete response, and 34 had a partial response.

Forty-three percent of responders maintained their response at 6 months, and 17% maintained their response at 12 months.

Serious AEs occurred in 58% of FL patients. The most common were diarrhea/colitis, pneumonia, renal insufficiency, rash, and sepsis.

AEs occurring in at least 20% of FL patients included diarrhea/colitis, nausea, fatigue, musculoskeletal pain, rash, neutropenia, cough, anemia, pyrexia, headache, mucositis, abdominal pain, vomiting, transaminase elevation, and thrombocytopenia.

Twenty-nine percent of FL patients discontinued duvelisib, and 23% had dose reductions. Most discontinuations were due to diarrhea/colitis and rash, and most dose reductions were due to transaminase elevation, diarrhea/colitis, lipase increase, and infection.

Micrograph showing CLL

The U.S. Food and Drug Administration (FDA) has approved duvelisib (Copiktra™), a dual PI3K delta/gamma inhibitor, for two indications.

Duvelisib has full FDA approval to treat adults with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have received at least two prior therapies.

Duvelisib also has accelerated approval to treat adults with relapsed or refractory follicular lymphoma (FL) who have received at least two prior systemic therapies.

Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit. Continued approval of duvelisib in FL may be contingent upon results of confirmatory trials verifying that the drug provides a clinical benefit.

Duvelisib will be available in the U.S. immediately, according to Verastem Inc., the company marketing the drug.

Verastem said it will help patients access duvelisib through the Verastem Cares™ program, which is designed to provide information and assistance to patients who are prescribed duvelisib.

The prescribing information for duvelisib includes a boxed warning detailing four fatal and/or serious toxicities associated with the drug—infections, diarrhea or colitis, cutaneous reactions, and pneumonitis.

Verastem said it is implementing an informational risk evaluation and mitigation strategy to provide appropriate dosing and safety information for duvelisib.

The recommended dose of duvelisib is 25 mg orally twice daily, taken continuously in 28-day treatment cycles.

The FDA assessed the new drug application for duvelisib under priority review. The FDA also granted duvelisib fast track designation in CLL and FL as well as orphan drug designation for CLL/SLL and FL.

The FDA’s approval of duvelisib is supported by data from the phase 3 DUO trial and the phase 2 DYNAMO trial. Updated results from both studies are available in the prescribing information for duvelisib.

DUO trial

DUO included 319 patients with CLL (n=312) or SLL (n=7) who had received at least one prior therapy. They were randomized to receive either duvelisib (25 mg orally twice daily) or ofatumumab (initial infusion of 300 mg followed by 7 weekly infusions and 4 monthly infusions of 2000 mg).

The following efficacy results were observed in patients who had received at least two prior therapies, which includes 95 patients in the duvelisib arm and 101 in the ofatumumab arm.

The overall response rate was 78% in the duvelisib arm and 39% in the ofatumumab arm. All responses in both arms were partial responses.

The median progression-free survival was 16.4 months with duvelisib and 9.1 months with ofatumumab (hazard ratio=0.40).

The safety results include all patients treated with duvelisib or ofatumumab.

Twelve percent of patients in the duvelisib arm had fatal adverse events (AEs) within 30 days of the last dose. The same was true of 4% of patients treated with ofatumumab.

Serious AEs occurred in 73% of patients treated with duvelisib. The most common were infection (38%) and diarrhea/colitis (23%).

Thirty-six percent of patients discontinued duvelisib. Most discontinuations were due to diarrhea/ colitis, infection, and rash. Twenty-nine percent of patients in the duvelisib arm required dose reductions, most often due to diarrhea/colitis and rash.

DYNAMO trial

DYNAMO enrolled patients with indolent non-Hodgkin lymphoma whose disease was refractory to both rituximab and chemotherapy or radioimmunotherapy.

There were 83 patients with FL. They had a median of 3 prior anticancer regimens (range, 1-10).

The patients received duvelisib at 25 mg orally twice daily until disease progression or unacceptable toxicity.

The overall response rate was 42%. One patient achieved a complete response, and 34 had a partial response.

Forty-three percent of responders maintained their response at 6 months, and 17% maintained their response at 12 months.

Serious AEs occurred in 58% of FL patients. The most common were diarrhea/colitis, pneumonia, renal insufficiency, rash, and sepsis.

AEs occurring in at least 20% of FL patients included diarrhea/colitis, nausea, fatigue, musculoskeletal pain, rash, neutropenia, cough, anemia, pyrexia, headache, mucositis, abdominal pain, vomiting, transaminase elevation, and thrombocytopenia.

Twenty-nine percent of FL patients discontinued duvelisib, and 23% had dose reductions. Most discontinuations were due to diarrhea/colitis and rash, and most dose reductions were due to transaminase elevation, diarrhea/colitis, lipase increase, and infection.

Photo from Business Wire

The Japanese Ministry of Health, Labour and Welfare has approved brentuximab vedotin (Adcetris) in combination with doxorubicin, vinblastine, and dacarbazine as a frontline treatment option for CD30-positive Hodgkin lymphoma (HL).

The approval was based on the phase 3 ECHELON-1 trial.

Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.

In this trial, researchers compared brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for 1334 patients with advanced HL.

The primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.

According to an independent review committee, A+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.

The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm.

There was no significant difference between the treatment arms when it came to response rates or overall survival.

The objective response rate was 86% in the A+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).

The interim 2-year overall survival rate was 97% in the A+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).

The overall incidence of adverse events (AEs) was 99% in the A+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.

Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with A+AVD, while pulmonary toxicity was more common with ABVD. 

Photo from Business Wire

The Japanese Ministry of Health, Labour and Welfare has approved brentuximab vedotin (Adcetris) in combination with doxorubicin, vinblastine, and dacarbazine as a frontline treatment option for CD30-positive Hodgkin lymphoma (HL).

The approval was based on the phase 3 ECHELON-1 trial.

Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.

In this trial, researchers compared brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for 1334 patients with advanced HL.

The primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.

According to an independent review committee, A+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.

The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm.

There was no significant difference between the treatment arms when it came to response rates or overall survival.

The objective response rate was 86% in the A+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).

The interim 2-year overall survival rate was 97% in the A+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).

The overall incidence of adverse events (AEs) was 99% in the A+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.

Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with A+AVD, while pulmonary toxicity was more common with ABVD. 

Photo from Business Wire

The Japanese Ministry of Health, Labour and Welfare has approved brentuximab vedotin (Adcetris) in combination with doxorubicin, vinblastine, and dacarbazine as a frontline treatment option for CD30-positive Hodgkin lymphoma (HL).

The approval was based on the phase 3 ECHELON-1 trial.

Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in The New England Journal of Medicine.

In this trial, researchers compared brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline treatment for 1334 patients with advanced HL.

The primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.

According to an independent review committee, A+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.

The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm.

There was no significant difference between the treatment arms when it came to response rates or overall survival.

The objective response rate was 86% in the A+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).

The interim 2-year overall survival rate was 97% in the A+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).

The overall incidence of adverse events (AEs) was 99% in the A+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.

Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with A+AVD, while pulmonary toxicity was more common with ABVD. 

Photo from Amgen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for three proposed biosimilars of pegfilgrastim—Ziextenzo, Pelmeg, and Fulphila.

If approved by the European Commission (EC), these products would be used for the same indication as the reference medicine, Neulasta (pegfilgrastim).

Neulasta has been EC-approved since 2002 to reduce the duration of neutropenia and the incidence of febrile neutropenia in adults who receive cytotoxic chemotherapy to treat malignancies except chronic myeloid leukemia and myelodysplastic syndromes.

According to the CHMP, data suggest that Ziextenzo, Pelmeg, and Fulphila all have quality, efficacy, and safety profiles comparable to Neulasta.

The EC is expected to make a decision on the approval of Ziextenzo, Pelmeg, and Fulphila within 67 days of the CHMP’s opinion.

The EC’s decision will apply to the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions based on the EC’s judgement.

Ziextenzo is being developed by Sandoz GmbH, Pelmeg is being developed by Cinfa Biotech S.L., and Fulphila is being developed by MYLAN S.A.S.

Photo from Amgen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for three proposed biosimilars of pegfilgrastim—Ziextenzo, Pelmeg, and Fulphila.

If approved by the European Commission (EC), these products would be used for the same indication as the reference medicine, Neulasta (pegfilgrastim).

Neulasta has been EC-approved since 2002 to reduce the duration of neutropenia and the incidence of febrile neutropenia in adults who receive cytotoxic chemotherapy to treat malignancies except chronic myeloid leukemia and myelodysplastic syndromes.

According to the CHMP, data suggest that Ziextenzo, Pelmeg, and Fulphila all have quality, efficacy, and safety profiles comparable to Neulasta.

The EC is expected to make a decision on the approval of Ziextenzo, Pelmeg, and Fulphila within 67 days of the CHMP’s opinion.

The EC’s decision will apply to the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions based on the EC’s judgement.

Ziextenzo is being developed by Sandoz GmbH, Pelmeg is being developed by Cinfa Biotech S.L., and Fulphila is being developed by MYLAN S.A.S.

Photo from Amgen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for three proposed biosimilars of pegfilgrastim—Ziextenzo, Pelmeg, and Fulphila.

If approved by the European Commission (EC), these products would be used for the same indication as the reference medicine, Neulasta (pegfilgrastim).

Neulasta has been EC-approved since 2002 to reduce the duration of neutropenia and the incidence of febrile neutropenia in adults who receive cytotoxic chemotherapy to treat malignancies except chronic myeloid leukemia and myelodysplastic syndromes.

According to the CHMP, data suggest that Ziextenzo, Pelmeg, and Fulphila all have quality, efficacy, and safety profiles comparable to Neulasta.

The EC is expected to make a decision on the approval of Ziextenzo, Pelmeg, and Fulphila within 67 days of the CHMP’s opinion.

The EC’s decision will apply to the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions based on the EC’s judgement.

Ziextenzo is being developed by Sandoz GmbH, Pelmeg is being developed by Cinfa Biotech S.L., and Fulphila is being developed by MYLAN S.A.S.

For elderly patients with untreated Hodgkin lymphoma (HL), adding brentuximab vedotin (Bv) before and after standard chemotherapy significantly improved survival, a recent study found.

In patients with low comorbidity scores, responses were even more robust, reported Andrew M. Evens, DO, of the Rutgers Cancer Institute of New Jersey in New Brunswick and his colleagues.

“Causes of poor outcomes for older patients with HL are not fully understood but have been attributed to a combination of factors, including presence of comorbidities, poorer performance status, disease and biological differences, inability to tolerate chemotherapy at the full dose, and increased treatment-related toxicities,” the authors wrote in the Journal of Clinical Oncology.

The primary goal of the study was to improve outcomes for untreated, older patients, a group that’s historically been a difficult-to-treat patient population.

The phase 2 trial included 48 elderly patients (median age, 69 years) with Hodgkin lymphoma. All patients underwent geriatric assessment for comorbidities and loss of activities of daily living. Treatment consisted of two doses of Bv followed by six cycles of doxorubicin, vinblastine, and dacarbazine (AVD), then four more doses of Bv (consolidation doses). The primary endpoint was complete remission at completion of AVD. Secondary outcomes included overall response rate, 2-year progression-free survival, 2-year overall survival, and safety.

Just over half of the patients (52%) completed all cycles of therapy, and almost three-quarters (72%) received at least one consolidation dose of Bv.

Among the first 23 evaluable patients, both the complete remission rate and overall response rate were 96%. Intention-to-treat survival rates for all 48 patients were 84% for 2-year progression-free survival and 93% for 2-year overall survival.

SOURCE: Evens AM et al. J Clin Oncol. 2018 Sep 4. doi: 10.1200/JCO.2018.79.0139

For elderly patients with untreated Hodgkin lymphoma (HL), adding brentuximab vedotin (Bv) before and after standard chemotherapy significantly improved survival, a recent study found.

In patients with low comorbidity scores, responses were even more robust, reported Andrew M. Evens, DO, of the Rutgers Cancer Institute of New Jersey in New Brunswick and his colleagues.

“Causes of poor outcomes for older patients with HL are not fully understood but have been attributed to a combination of factors, including presence of comorbidities, poorer performance status, disease and biological differences, inability to tolerate chemotherapy at the full dose, and increased treatment-related toxicities,” the authors wrote in the Journal of Clinical Oncology.

The primary goal of the study was to improve outcomes for untreated, older patients, a group that’s historically been a difficult-to-treat patient population.

The phase 2 trial included 48 elderly patients (median age, 69 years) with Hodgkin lymphoma. All patients underwent geriatric assessment for comorbidities and loss of activities of daily living. Treatment consisted of two doses of Bv followed by six cycles of doxorubicin, vinblastine, and dacarbazine (AVD), then four more doses of Bv (consolidation doses). The primary endpoint was complete remission at completion of AVD. Secondary outcomes included overall response rate, 2-year progression-free survival, 2-year overall survival, and safety.

Just over half of the patients (52%) completed all cycles of therapy, and almost three-quarters (72%) received at least one consolidation dose of Bv.

Among the first 23 evaluable patients, both the complete remission rate and overall response rate were 96%. Intention-to-treat survival rates for all 48 patients were 84% for 2-year progression-free survival and 93% for 2-year overall survival.

SOURCE: Evens AM et al. J Clin Oncol. 2018 Sep 4. doi: 10.1200/JCO.2018.79.0139

For elderly patients with untreated Hodgkin lymphoma (HL), adding brentuximab vedotin (Bv) before and after standard chemotherapy significantly improved survival, a recent study found.

In patients with low comorbidity scores, responses were even more robust, reported Andrew M. Evens, DO, of the Rutgers Cancer Institute of New Jersey in New Brunswick and his colleagues.

“Causes of poor outcomes for older patients with HL are not fully understood but have been attributed to a combination of factors, including presence of comorbidities, poorer performance status, disease and biological differences, inability to tolerate chemotherapy at the full dose, and increased treatment-related toxicities,” the authors wrote in the Journal of Clinical Oncology.

The primary goal of the study was to improve outcomes for untreated, older patients, a group that’s historically been a difficult-to-treat patient population.

The phase 2 trial included 48 elderly patients (median age, 69 years) with Hodgkin lymphoma. All patients underwent geriatric assessment for comorbidities and loss of activities of daily living. Treatment consisted of two doses of Bv followed by six cycles of doxorubicin, vinblastine, and dacarbazine (AVD), then four more doses of Bv (consolidation doses). The primary endpoint was complete remission at completion of AVD. Secondary outcomes included overall response rate, 2-year progression-free survival, 2-year overall survival, and safety.

Just over half of the patients (52%) completed all cycles of therapy, and almost three-quarters (72%) received at least one consolidation dose of Bv.

Among the first 23 evaluable patients, both the complete remission rate and overall response rate were 96%. Intention-to-treat survival rates for all 48 patients were 84% for 2-year progression-free survival and 93% for 2-year overall survival.

SOURCE: Evens AM et al. J Clin Oncol. 2018 Sep 4. doi: 10.1200/JCO.2018.79.0139

Photo courtesy of Abbvie

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that the European Commission (EC) approve a new indication for venetoclax (Venclyxto®).

AbbVie is seeking EC approval for venetoclax in combination with rituximab for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.

The EC typically makes an approval decision within 67 days of the CHMP’s opinion.

The EC’s decision will apply to the European Union, Norway, Iceland, and Liechtenstein.

Venetoclax is already EC-approved as monotherapy for:

• Adults with CLL who have 17p deletion or TP53 mutation and are unsuitable for or have failed treatment with a B-cell receptor pathway inhibitor
• Adults with CLL who do not have 17p deletion or TP53 mutation but have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.

The CHMP’s recommendation to approve venetoclax in combination with rituximab is supported by the phase 3 MURANO trial. Results from MURANO were published in The New England Journal of Medicine in March.

The trial included 389 CLL patients who were randomized to receive venetoclax plus rituximab (VEN+R) or bendamustine plus rituximab (B+R). The median follow-up was 23.8 months.

According to investigators, the median progression-free survival was not reached in the VEN+R arm and was 17.0 months in the B+R arm (hazard ratio, 0.17; P<0.0001).

According to an independent review committee, the median progression-free survival was not reached in the VEN+R arm and was 18.1 months in the B+R arm (hazard ratio, 0.20; P<0.0001).

Grade 3/4 adverse events (AEs) with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) included:

• Neutropenia (57.7% and 38.8%)
• Infections and infestations (17.5% and 21.8%)
• Anemia (10.8% and 13.8%)
• Thrombocytopenia (5.7% and 10.1%)
• Febrile neutropenia (3.6% and 9.6%)
• Pneumonia (5.2% and 8.0%)
• Infusion-related reaction (1.5% and 5.3%)
• Tumor lysis syndrome (3.1% and 1.1%)
• Hypotension (0% and 2.7%)
• Hyperglycemia (2.1% and 0%)
• Hypogammaglobulinemia (2.1% and 0%).

Serious AEs with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) were:

• Pneumonia (8.2% and 8.0%)
• Febrile neutropenia (3.6% and 8.5%)
• Pyrexia (2.6% and 6.9%)
• Anemia (1.5% and 2.7%)
• Infusion-related reaction (0.5% and 3.2%)
• Sepsis (0.5% and 2.1%)
• Tumor lysis syndrome (2.1% and 0.5%)
• Hypotension (0% and 2.7%).

Fatal AEs occurred in 5.2% of patients in the VEN+R arm and 5.9% in the B+R arm.

Fatal AEs in the VEN+R arm included pneumonia (n=3), sepsis (n=1), thrombocytopenia (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1). Two cases of pneumonia occurred in the setting of progression/Richter transformation.

Photo courtesy of Abbvie

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that the European Commission (EC) approve a new indication for venetoclax (Venclyxto®).

AbbVie is seeking EC approval for venetoclax in combination with rituximab for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.

The EC typically makes an approval decision within 67 days of the CHMP’s opinion.

The EC’s decision will apply to the European Union, Norway, Iceland, and Liechtenstein.

Venetoclax is already EC-approved as monotherapy for:

• Adults with CLL who have 17p deletion or TP53 mutation and are unsuitable for or have failed treatment with a B-cell receptor pathway inhibitor
• Adults with CLL who do not have 17p deletion or TP53 mutation but have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.

The CHMP’s recommendation to approve venetoclax in combination with rituximab is supported by the phase 3 MURANO trial. Results from MURANO were published in The New England Journal of Medicine in March.

The trial included 389 CLL patients who were randomized to receive venetoclax plus rituximab (VEN+R) or bendamustine plus rituximab (B+R). The median follow-up was 23.8 months.

According to investigators, the median progression-free survival was not reached in the VEN+R arm and was 17.0 months in the B+R arm (hazard ratio, 0.17; P<0.0001).

According to an independent review committee, the median progression-free survival was not reached in the VEN+R arm and was 18.1 months in the B+R arm (hazard ratio, 0.20; P<0.0001).

Grade 3/4 adverse events (AEs) with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) included:

• Neutropenia (57.7% and 38.8%)
• Infections and infestations (17.5% and 21.8%)
• Anemia (10.8% and 13.8%)
• Thrombocytopenia (5.7% and 10.1%)
• Febrile neutropenia (3.6% and 9.6%)
• Pneumonia (5.2% and 8.0%)
• Infusion-related reaction (1.5% and 5.3%)
• Tumor lysis syndrome (3.1% and 1.1%)
• Hypotension (0% and 2.7%)
• Hyperglycemia (2.1% and 0%)
• Hypogammaglobulinemia (2.1% and 0%).

Serious AEs with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) were:

• Pneumonia (8.2% and 8.0%)
• Febrile neutropenia (3.6% and 8.5%)
• Pyrexia (2.6% and 6.9%)
• Anemia (1.5% and 2.7%)
• Infusion-related reaction (0.5% and 3.2%)
• Sepsis (0.5% and 2.1%)
• Tumor lysis syndrome (2.1% and 0.5%)
• Hypotension (0% and 2.7%).

Fatal AEs occurred in 5.2% of patients in the VEN+R arm and 5.9% in the B+R arm.

Fatal AEs in the VEN+R arm included pneumonia (n=3), sepsis (n=1), thrombocytopenia (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1). Two cases of pneumonia occurred in the setting of progression/Richter transformation.

Photo courtesy of Abbvie

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that the European Commission (EC) approve a new indication for venetoclax (Venclyxto®).

AbbVie is seeking EC approval for venetoclax in combination with rituximab for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.

The EC typically makes an approval decision within 67 days of the CHMP’s opinion.

The EC’s decision will apply to the European Union, Norway, Iceland, and Liechtenstein.

Venetoclax is already EC-approved as monotherapy for:

• Adults with CLL who have 17p deletion or TP53 mutation and are unsuitable for or have failed treatment with a B-cell receptor pathway inhibitor
• Adults with CLL who do not have 17p deletion or TP53 mutation but have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.

The CHMP’s recommendation to approve venetoclax in combination with rituximab is supported by the phase 3 MURANO trial. Results from MURANO were published in The New England Journal of Medicine in March.

The trial included 389 CLL patients who were randomized to receive venetoclax plus rituximab (VEN+R) or bendamustine plus rituximab (B+R). The median follow-up was 23.8 months.

According to investigators, the median progression-free survival was not reached in the VEN+R arm and was 17.0 months in the B+R arm (hazard ratio, 0.17; P<0.0001).

According to an independent review committee, the median progression-free survival was not reached in the VEN+R arm and was 18.1 months in the B+R arm (hazard ratio, 0.20; P<0.0001).

Grade 3/4 adverse events (AEs) with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) included:

• Neutropenia (57.7% and 38.8%)
• Infections and infestations (17.5% and 21.8%)
• Anemia (10.8% and 13.8%)
• Thrombocytopenia (5.7% and 10.1%)
• Febrile neutropenia (3.6% and 9.6%)
• Pneumonia (5.2% and 8.0%)
• Infusion-related reaction (1.5% and 5.3%)
• Tumor lysis syndrome (3.1% and 1.1%)
• Hypotension (0% and 2.7%)
• Hyperglycemia (2.1% and 0%)
• Hypogammaglobulinemia (2.1% and 0%).

Serious AEs with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) were:

• Pneumonia (8.2% and 8.0%)
• Febrile neutropenia (3.6% and 8.5%)
• Pyrexia (2.6% and 6.9%)
• Anemia (1.5% and 2.7%)
• Infusion-related reaction (0.5% and 3.2%)
• Sepsis (0.5% and 2.1%)
• Tumor lysis syndrome (2.1% and 0.5%)
• Hypotension (0% and 2.7%).

Fatal AEs occurred in 5.2% of patients in the VEN+R arm and 5.9% in the B+R arm.

Fatal AEs in the VEN+R arm included pneumonia (n=3), sepsis (n=1), thrombocytopenia (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1). Two cases of pneumonia occurred in the setting of progression/Richter transformation.

mycosis fungoides

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for mogamulizumab (Poteligeo).

Kyowa Kirin Limited is seeking European Commission (EC) approval for mogamulizumab as a treatment for adults with mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy.

The CHMP’s recommendation to approve mogamulizumab will be reviewed by the EC, and the EC is expected to make its decision about the drug by the end of this year.

The decision will apply to the European Union, Norway, Iceland, and Liechtenstein.

The CHMP’s recommendation for mogamulizumab is supported by the phase 3 MAVORIC trial. Results from this trial were published in The Lancet Oncology in August.

MAVORIC was a comparison of mogamulizumab and vorinostat in 372 adults with MF or SS who had received at least one prior systemic therapy.

Mogamulizumab provided a significant improvement in progression-free survival (PFS), the study’s primary endpoint.

According to investigators, the median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).

According to independent review, the median PFS was 6.7 months and 3.8 months, respectively (hazard ratio=0.64, P<0.0007).

There was a significant improvement in overall response rate (ORR) with mogamulizumab.

According to independent review, the global ORR was 23% (43/186) in the mogamulizumab arm and 4% (7/186) in the vorinostat arm (risk ratio=19.4, P<0.0001).

According to investigators, the global ORR was 28% (52/186) and 5% (9/186), respectively (risk ratio=23.1, P<0.0001).

For patients with MF, the investigator-assessed ORR was 21% (22/105) with mogamulizumab and 7% (7/99) with vorinostat.

For SS patients, the investigator-assessed ORR was 37% (30/81) and 2% (2/87), respectively.

Grade 3 adverse events (AEs) in the mogamulizumab arm included drug eruptions (n=8), hypertension (n=8), pneumonia (n=6), fatigue (n=3), cellulitis (n=3), infusion-related reactions (n=3), sepsis (n=2), decreased appetite (n=2), AST increase (n=2), weight decrease (n=1), pyrexia (n=1), constipation (n=1), nausea (n=1), and diarrhea (n=1).

Grade 4 AEs with mogamulizumab were cellulitis (n=1) and pneumonia (n=1). Grade 5 AEs included pneumonia (n=1) and sepsis (n=1).

mycosis fungoides

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for mogamulizumab (Poteligeo).

Kyowa Kirin Limited is seeking European Commission (EC) approval for mogamulizumab as a treatment for adults with mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy.

The CHMP’s recommendation to approve mogamulizumab will be reviewed by the EC, and the EC is expected to make its decision about the drug by the end of this year.

The decision will apply to the European Union, Norway, Iceland, and Liechtenstein.

The CHMP’s recommendation for mogamulizumab is supported by the phase 3 MAVORIC trial. Results from this trial were published in The Lancet Oncology in August.

MAVORIC was a comparison of mogamulizumab and vorinostat in 372 adults with MF or SS who had received at least one prior systemic therapy.

Mogamulizumab provided a significant improvement in progression-free survival (PFS), the study’s primary endpoint.

According to investigators, the median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).

According to independent review, the median PFS was 6.7 months and 3.8 months, respectively (hazard ratio=0.64, P<0.0007).

There was a significant improvement in overall response rate (ORR) with mogamulizumab.

According to independent review, the global ORR was 23% (43/186) in the mogamulizumab arm and 4% (7/186) in the vorinostat arm (risk ratio=19.4, P<0.0001).

According to investigators, the global ORR was 28% (52/186) and 5% (9/186), respectively (risk ratio=23.1, P<0.0001).

For patients with MF, the investigator-assessed ORR was 21% (22/105) with mogamulizumab and 7% (7/99) with vorinostat.

For SS patients, the investigator-assessed ORR was 37% (30/81) and 2% (2/87), respectively.

Grade 3 adverse events (AEs) in the mogamulizumab arm included drug eruptions (n=8), hypertension (n=8), pneumonia (n=6), fatigue (n=3), cellulitis (n=3), infusion-related reactions (n=3), sepsis (n=2), decreased appetite (n=2), AST increase (n=2), weight decrease (n=1), pyrexia (n=1), constipation (n=1), nausea (n=1), and diarrhea (n=1).

Grade 4 AEs with mogamulizumab were cellulitis (n=1) and pneumonia (n=1). Grade 5 AEs included pneumonia (n=1) and sepsis (n=1).

mycosis fungoides

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for mogamulizumab (Poteligeo).

Kyowa Kirin Limited is seeking European Commission (EC) approval for mogamulizumab as a treatment for adults with mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy.

The CHMP’s recommendation to approve mogamulizumab will be reviewed by the EC, and the EC is expected to make its decision about the drug by the end of this year.

The decision will apply to the European Union, Norway, Iceland, and Liechtenstein.

The CHMP’s recommendation for mogamulizumab is supported by the phase 3 MAVORIC trial. Results from this trial were published in The Lancet Oncology in August.

MAVORIC was a comparison of mogamulizumab and vorinostat in 372 adults with MF or SS who had received at least one prior systemic therapy.

Mogamulizumab provided a significant improvement in progression-free survival (PFS), the study’s primary endpoint.

According to investigators, the median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).

According to independent review, the median PFS was 6.7 months and 3.8 months, respectively (hazard ratio=0.64, P<0.0007).

There was a significant improvement in overall response rate (ORR) with mogamulizumab.

According to independent review, the global ORR was 23% (43/186) in the mogamulizumab arm and 4% (7/186) in the vorinostat arm (risk ratio=19.4, P<0.0001).

According to investigators, the global ORR was 28% (52/186) and 5% (9/186), respectively (risk ratio=23.1, P<0.0001).

For patients with MF, the investigator-assessed ORR was 21% (22/105) with mogamulizumab and 7% (7/99) with vorinostat.

For SS patients, the investigator-assessed ORR was 37% (30/81) and 2% (2/87), respectively.

Grade 3 adverse events (AEs) in the mogamulizumab arm included drug eruptions (n=8), hypertension (n=8), pneumonia (n=6), fatigue (n=3), cellulitis (n=3), infusion-related reactions (n=3), sepsis (n=2), decreased appetite (n=2), AST increase (n=2), weight decrease (n=1), pyrexia (n=1), constipation (n=1), nausea (n=1), and diarrhea (n=1).

Grade 4 AEs with mogamulizumab were cellulitis (n=1) and pneumonia (n=1). Grade 5 AEs included pneumonia (n=1) and sepsis (n=1).

Mantle cell lymphoma

Researchers say they have found evidence to suggest that patients with mantle cell lymphoma (MCL) should be evaluated for TP53 mutation and complex karyotype (CK) simultaneously before treatment.

The team’s study showed that TP53 mutation and CK occurred independently, but patients with both characteristics had poor prognosis.

All patients with TP53 mutation and CK died within 1.2 years of diagnosis, whereas about 94% of patients with neither characteristic were still alive at 2 years.

The researchers also found that, by combining TP53 mutation and CK, patients could be stratified into three prognostic groups that had distinct outcomes, regardless of treatment.

Vít Procházka, MD, PhD, of Palacký University in Olomouc, Czech Republic, and his colleagues reported these findings in Clinical Lymphoma, Myeloma & Leukemia.

The study included 74 consecutive adults newly diagnosed with MCL from 2000 through 2014. Seventy-three patients were treated with a rituximab-containing regimen. One patient, who did not have TP53 mutation or CK, was under observation without therapy.

Altogether, 48 patients (64.9%) had biological material available to perform analyses for TP53 mutation and CK. Of those, 4 patients were found to have both TP53 mutation and CK, 12 had one of the two markers, and 32 had neither.

While all patients with both markers died within 1.2 years, 2-year overall survival was 50.0% for those with one marker and 93.8% for those with neither marker (P<0.001).

Progression-free survival analyses showed similar results. The 2-year progression-free survival rate was 41.7% for patients with one marker and 78% for patients with neither marker (P<0.001).

Multivariate analysis showed that both TP53 mutation and CK were predictors of inferior progression-free survival and overall survival, independent of age and scores on the MCL International Prognostic Index.

While larger studies are needed to confirm these results, the researchers suggested that novel treatment approaches might be warranted for patients in the highest risk subgroup.

“The patients harboring the negative prognostic markers [TP53 mutation] and CK might be indicated for a novel induction treatment strategy probably in combination with maintenance therapy different from rituximab,” the researchers said.

This study was supported by grants from the Czech Ministry of Health and Palacký University. The researchers reported having no conflicts of interest.

Mantle cell lymphoma

Researchers say they have found evidence to suggest that patients with mantle cell lymphoma (MCL) should be evaluated for TP53 mutation and complex karyotype (CK) simultaneously before treatment.

The team’s study showed that TP53 mutation and CK occurred independently, but patients with both characteristics had poor prognosis.

All patients with TP53 mutation and CK died within 1.2 years of diagnosis, whereas about 94% of patients with neither characteristic were still alive at 2 years.

The researchers also found that, by combining TP53 mutation and CK, patients could be stratified into three prognostic groups that had distinct outcomes, regardless of treatment.

Vít Procházka, MD, PhD, of Palacký University in Olomouc, Czech Republic, and his colleagues reported these findings in Clinical Lymphoma, Myeloma & Leukemia.

The study included 74 consecutive adults newly diagnosed with MCL from 2000 through 2014. Seventy-three patients were treated with a rituximab-containing regimen. One patient, who did not have TP53 mutation or CK, was under observation without therapy.

Altogether, 48 patients (64.9%) had biological material available to perform analyses for TP53 mutation and CK. Of those, 4 patients were found to have both TP53 mutation and CK, 12 had one of the two markers, and 32 had neither.

While all patients with both markers died within 1.2 years, 2-year overall survival was 50.0% for those with one marker and 93.8% for those with neither marker (P<0.001).

Progression-free survival analyses showed similar results. The 2-year progression-free survival rate was 41.7% for patients with one marker and 78% for patients with neither marker (P<0.001).

Multivariate analysis showed that both TP53 mutation and CK were predictors of inferior progression-free survival and overall survival, independent of age and scores on the MCL International Prognostic Index.

While larger studies are needed to confirm these results, the researchers suggested that novel treatment approaches might be warranted for patients in the highest risk subgroup.

“The patients harboring the negative prognostic markers [TP53 mutation] and CK might be indicated for a novel induction treatment strategy probably in combination with maintenance therapy different from rituximab,” the researchers said.

This study was supported by grants from the Czech Ministry of Health and Palacký University. The researchers reported having no conflicts of interest.

Mantle cell lymphoma

Researchers say they have found evidence to suggest that patients with mantle cell lymphoma (MCL) should be evaluated for TP53 mutation and complex karyotype (CK) simultaneously before treatment.

The team’s study showed that TP53 mutation and CK occurred independently, but patients with both characteristics had poor prognosis.

All patients with TP53 mutation and CK died within 1.2 years of diagnosis, whereas about 94% of patients with neither characteristic were still alive at 2 years.

The researchers also found that, by combining TP53 mutation and CK, patients could be stratified into three prognostic groups that had distinct outcomes, regardless of treatment.

Vít Procházka, MD, PhD, of Palacký University in Olomouc, Czech Republic, and his colleagues reported these findings in Clinical Lymphoma, Myeloma & Leukemia.

The study included 74 consecutive adults newly diagnosed with MCL from 2000 through 2014. Seventy-three patients were treated with a rituximab-containing regimen. One patient, who did not have TP53 mutation or CK, was under observation without therapy.

Altogether, 48 patients (64.9%) had biological material available to perform analyses for TP53 mutation and CK. Of those, 4 patients were found to have both TP53 mutation and CK, 12 had one of the two markers, and 32 had neither.

While all patients with both markers died within 1.2 years, 2-year overall survival was 50.0% for those with one marker and 93.8% for those with neither marker (P<0.001).

Progression-free survival analyses showed similar results. The 2-year progression-free survival rate was 41.7% for patients with one marker and 78% for patients with neither marker (P<0.001).

Multivariate analysis showed that both TP53 mutation and CK were predictors of inferior progression-free survival and overall survival, independent of age and scores on the MCL International Prognostic Index.

While larger studies are needed to confirm these results, the researchers suggested that novel treatment approaches might be warranted for patients in the highest risk subgroup.

“The patients harboring the negative prognostic markers [TP53 mutation] and CK might be indicated for a novel induction treatment strategy probably in combination with maintenance therapy different from rituximab,” the researchers said.

This study was supported by grants from the Czech Ministry of Health and Palacký University. The researchers reported having no conflicts of interest.

Micrograph showing CLL

New research has linked stress levels to markers of progressive disease in patients with chronic lymphocytic leukemia (CLL).

Researchers found that CLL patients who reported more stress also had higher absolute lymphocyte counts and elevated levels of three other markers of more advanced disease—tumor necrosis factor-α (TNFα), interleukin 16 (IL-16), and chemokine ligand 3 (CCL3).

“All four variables we measured are related to prognosis in CLL patients, so they have a lot of relevance,” said study author Barbara L. Andersen, PhD, of The Ohio State University in Columbus.

She and her colleagues described this research in Cancer.

The study involved 96 patients with relapsed/refractory CLL who were entering a phase 2 trial of ibrutinib (NCT01589302). Data collection for this study was done before patients received their first dose of ibrutinib.

All patients completed a survey that measured CLL-related stress. They were asked questions like how often they had intrusive thoughts about their disease, how often they tried to avoid thinking about it, and how often they felt jumpy and easily startled.

The researchers used blood samples to determine patients’ absolute lymphocyte counts and to measure levels of eight cytokines known to promote unhealthy levels of inflammation—IL-6, IL-10, IL-16, TNFα, a proliferation‐inducing ligand (APRIL), B‐cell activating factor (BAFF), vascular endothelial growth factor (VEGF), and CCL3.

In an analysis controlling for demographic characteristics, comorbidities, the presence of 17p deletion, and correlates of inflammation, higher stress was significantly associated with higher:

• Absolute lymphocyte counts (P<0.05)
• Levels of TNFα (P<0.05)
• Levels of IL‐16 (P<0.01)
• Levels of CCL3 (P<0.05).

“The fact that stress shows an effect on CLL even after we controlled for other factors suggests it may be relevant to the course of CLL,” Dr. Andersen said.

She added that the researchers are still following these patients and will examine the relationship between stress and disease markers throughout treatment.

This study was supported by the National Cancer Institute, Pharmacylics (the company developing ibrutinib), and a Pelotonia Idea Award from The Ohio State University Comprehensive Cancer Center.

Micrograph showing CLL

New research has linked stress levels to markers of progressive disease in patients with chronic lymphocytic leukemia (CLL).

Researchers found that CLL patients who reported more stress also had higher absolute lymphocyte counts and elevated levels of three other markers of more advanced disease—tumor necrosis factor-α (TNFα), interleukin 16 (IL-16), and chemokine ligand 3 (CCL3).

“All four variables we measured are related to prognosis in CLL patients, so they have a lot of relevance,” said study author Barbara L. Andersen, PhD, of The Ohio State University in Columbus.

She and her colleagues described this research in Cancer.

The study involved 96 patients with relapsed/refractory CLL who were entering a phase 2 trial of ibrutinib (NCT01589302). Data collection for this study was done before patients received their first dose of ibrutinib.

All patients completed a survey that measured CLL-related stress. They were asked questions like how often they had intrusive thoughts about their disease, how often they tried to avoid thinking about it, and how often they felt jumpy and easily startled.

The researchers used blood samples to determine patients’ absolute lymphocyte counts and to measure levels of eight cytokines known to promote unhealthy levels of inflammation—IL-6, IL-10, IL-16, TNFα, a proliferation‐inducing ligand (APRIL), B‐cell activating factor (BAFF), vascular endothelial growth factor (VEGF), and CCL3.

In an analysis controlling for demographic characteristics, comorbidities, the presence of 17p deletion, and correlates of inflammation, higher stress was significantly associated with higher:

• Absolute lymphocyte counts (P<0.05)
• Levels of TNFα (P<0.05)
• Levels of IL‐16 (P<0.01)
• Levels of CCL3 (P<0.05).

“The fact that stress shows an effect on CLL even after we controlled for other factors suggests it may be relevant to the course of CLL,” Dr. Andersen said.

She added that the researchers are still following these patients and will examine the relationship between stress and disease markers throughout treatment.

This study was supported by the National Cancer Institute, Pharmacylics (the company developing ibrutinib), and a Pelotonia Idea Award from The Ohio State University Comprehensive Cancer Center.

Micrograph showing CLL

New research has linked stress levels to markers of progressive disease in patients with chronic lymphocytic leukemia (CLL).

Researchers found that CLL patients who reported more stress also had higher absolute lymphocyte counts and elevated levels of three other markers of more advanced disease—tumor necrosis factor-α (TNFα), interleukin 16 (IL-16), and chemokine ligand 3 (CCL3).

“All four variables we measured are related to prognosis in CLL patients, so they have a lot of relevance,” said study author Barbara L. Andersen, PhD, of The Ohio State University in Columbus.

She and her colleagues described this research in Cancer.

The study involved 96 patients with relapsed/refractory CLL who were entering a phase 2 trial of ibrutinib (NCT01589302). Data collection for this study was done before patients received their first dose of ibrutinib.

All patients completed a survey that measured CLL-related stress. They were asked questions like how often they had intrusive thoughts about their disease, how often they tried to avoid thinking about it, and how often they felt jumpy and easily startled.

The researchers used blood samples to determine patients’ absolute lymphocyte counts and to measure levels of eight cytokines known to promote unhealthy levels of inflammation—IL-6, IL-10, IL-16, TNFα, a proliferation‐inducing ligand (APRIL), B‐cell activating factor (BAFF), vascular endothelial growth factor (VEGF), and CCL3.

In an analysis controlling for demographic characteristics, comorbidities, the presence of 17p deletion, and correlates of inflammation, higher stress was significantly associated with higher:

• Absolute lymphocyte counts (P<0.05)
• Levels of TNFα (P<0.05)
• Levels of IL‐16 (P<0.01)
• Levels of CCL3 (P<0.05).

“The fact that stress shows an effect on CLL even after we controlled for other factors suggests it may be relevant to the course of CLL,” Dr. Andersen said.

She added that the researchers are still following these patients and will examine the relationship between stress and disease markers throughout treatment.

This study was supported by the National Cancer Institute, Pharmacylics (the company developing ibrutinib), and a Pelotonia Idea Award from The Ohio State University Comprehensive Cancer Center.

Photo from Novartis

The National Institute for Health and Care Excellence (NICE) has issued a draft guidance saying it cannot recommend tisagenlecleucel (Kymriah) as a treatment for adults with diffuse large B-cell lymphoma (DLBCL).

Tisagenlecleucel is a chimeric antigen receptor (CAR) T-cell therapy that was recently approved by the European Commission (EC) to treat adults with relapsed or refractory DLBCL who have received two or more lines of systemic therapy.

Tisagenlecleucel is also EC-approved to treat patients up to 25 years of age who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant, or in second or later relapse.

Earlier this month, the National Health Service (NHS) of England announced that tisagenlecleucel will be made available for these ALL patients through the Cancer Drugs Fund.

However, NICE’s new draft guidance, issued September 19, says tisagenlecleucel cannot be made available for adults with relapsed/refractory DLBCL who have received two or more lines of systemic therapy.

NICE noted that there is no standard treatment for this patient group, and salvage chemotherapy is the most common treatment option.

Although the latest results from the JULIET trial¹ suggest tisagenlecleucel can produce responses in patients with relapsed/refractory DLBCL, there are no data comparing tisagenlecleucel with salvage chemotherapy.

In addition, tisagenlecleucel cannot be considered a life-extending treatment at the end of life, according to NICE criteria.

Furthermore, NICE said all cost-effectiveness estimates for tisagenlecleucel are above the range NICE normally considers acceptable, and tisagenlecleucel does not meet criteria for inclusion in the Cancer Drugs Fund.

The list price for tisagenlecleucel is £282,000. However, Novartis, the company developing tisagenlecleucel, has a confidential commercial arrangement with the NHS that lowers the price of tisagenlecleucel for the ALL indication. This arrangement would apply if tisagenlecleucel were recommended for the DLBCL indication.

All of the aforementioned issues aside, NICE said it does recognize that tisagenlecleucel has significant clinical benefits, and the agency welcomes further discussions on the CAR T-cell therapy’s cost-effectiveness.

NICE will consider comments on its draft guidance for tisagenlecleucel, together with any new evidence, at its next meeting on October 23, 2018.

Last month, NICE expressed similar sentiments about another CAR T-cell therapy, axicabtagene ciloleucel (Yescarta).

Axicabtagene ciloleucel is EC-approved to treat patients with relapsed/refractory DLBCL or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy.

However, NICE said it isn’t clear how much of a benefit axicabtagene ciloleucel may provide over salvage chemotherapy. Additionally, the cost of axicabtagene ciloleucel is too high for it to be considered a cost-effective use of NHS resources, and the therapy does not meet criteria for inclusion in the Cancer Drugs Fund.

1. Borchmann P et al. AN UPDATED ANALYSIS OF JULIET, A GLOBAL PIVOTAL PHASE 2 TRIAL OF TISAGENLECLEUCEL IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL). EHA 2018. Abstract S799.

Photo from Novartis

The National Institute for Health and Care Excellence (NICE) has issued a draft guidance saying it cannot recommend tisagenlecleucel (Kymriah) as a treatment for adults with diffuse large B-cell lymphoma (DLBCL).

Tisagenlecleucel is a chimeric antigen receptor (CAR) T-cell therapy that was recently approved by the European Commission (EC) to treat adults with relapsed or refractory DLBCL who have received two or more lines of systemic therapy.

Tisagenlecleucel is also EC-approved to treat patients up to 25 years of age who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant, or in second or later relapse.

Earlier this month, the National Health Service (NHS) of England announced that tisagenlecleucel will be made available for these ALL patients through the Cancer Drugs Fund.

However, NICE’s new draft guidance, issued September 19, says tisagenlecleucel cannot be made available for adults with relapsed/refractory DLBCL who have received two or more lines of systemic therapy.

NICE noted that there is no standard treatment for this patient group, and salvage chemotherapy is the most common treatment option.

Although the latest results from the JULIET trial¹ suggest tisagenlecleucel can produce responses in patients with relapsed/refractory DLBCL, there are no data comparing tisagenlecleucel with salvage chemotherapy.

In addition, tisagenlecleucel cannot be considered a life-extending treatment at the end of life, according to NICE criteria.

Furthermore, NICE said all cost-effectiveness estimates for tisagenlecleucel are above the range NICE normally considers acceptable, and tisagenlecleucel does not meet criteria for inclusion in the Cancer Drugs Fund.

The list price for tisagenlecleucel is £282,000. However, Novartis, the company developing tisagenlecleucel, has a confidential commercial arrangement with the NHS that lowers the price of tisagenlecleucel for the ALL indication. This arrangement would apply if tisagenlecleucel were recommended for the DLBCL indication.

All of the aforementioned issues aside, NICE said it does recognize that tisagenlecleucel has significant clinical benefits, and the agency welcomes further discussions on the CAR T-cell therapy’s cost-effectiveness.

NICE will consider comments on its draft guidance for tisagenlecleucel, together with any new evidence, at its next meeting on October 23, 2018.

Last month, NICE expressed similar sentiments about another CAR T-cell therapy, axicabtagene ciloleucel (Yescarta).

Axicabtagene ciloleucel is EC-approved to treat patients with relapsed/refractory DLBCL or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy.

However, NICE said it isn’t clear how much of a benefit axicabtagene ciloleucel may provide over salvage chemotherapy. Additionally, the cost of axicabtagene ciloleucel is too high for it to be considered a cost-effective use of NHS resources, and the therapy does not meet criteria for inclusion in the Cancer Drugs Fund.

1. Borchmann P et al. AN UPDATED ANALYSIS OF JULIET, A GLOBAL PIVOTAL PHASE 2 TRIAL OF TISAGENLECLEUCEL IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL). EHA 2018. Abstract S799.

Photo from Novartis

The National Institute for Health and Care Excellence (NICE) has issued a draft guidance saying it cannot recommend tisagenlecleucel (Kymriah) as a treatment for adults with diffuse large B-cell lymphoma (DLBCL).

Tisagenlecleucel is a chimeric antigen receptor (CAR) T-cell therapy that was recently approved by the European Commission (EC) to treat adults with relapsed or refractory DLBCL who have received two or more lines of systemic therapy.

Tisagenlecleucel is also EC-approved to treat patients up to 25 years of age who have B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant, or in second or later relapse.

Earlier this month, the National Health Service (NHS) of England announced that tisagenlecleucel will be made available for these ALL patients through the Cancer Drugs Fund.

However, NICE’s new draft guidance, issued September 19, says tisagenlecleucel cannot be made available for adults with relapsed/refractory DLBCL who have received two or more lines of systemic therapy.

NICE noted that there is no standard treatment for this patient group, and salvage chemotherapy is the most common treatment option.

Although the latest results from the JULIET trial¹ suggest tisagenlecleucel can produce responses in patients with relapsed/refractory DLBCL, there are no data comparing tisagenlecleucel with salvage chemotherapy.

In addition, tisagenlecleucel cannot be considered a life-extending treatment at the end of life, according to NICE criteria.

Furthermore, NICE said all cost-effectiveness estimates for tisagenlecleucel are above the range NICE normally considers acceptable, and tisagenlecleucel does not meet criteria for inclusion in the Cancer Drugs Fund.

The list price for tisagenlecleucel is £282,000. However, Novartis, the company developing tisagenlecleucel, has a confidential commercial arrangement with the NHS that lowers the price of tisagenlecleucel for the ALL indication. This arrangement would apply if tisagenlecleucel were recommended for the DLBCL indication.

All of the aforementioned issues aside, NICE said it does recognize that tisagenlecleucel has significant clinical benefits, and the agency welcomes further discussions on the CAR T-cell therapy’s cost-effectiveness.

NICE will consider comments on its draft guidance for tisagenlecleucel, together with any new evidence, at its next meeting on October 23, 2018.

Last month, NICE expressed similar sentiments about another CAR T-cell therapy, axicabtagene ciloleucel (Yescarta).

Axicabtagene ciloleucel is EC-approved to treat patients with relapsed/refractory DLBCL or primary mediastinal B-cell lymphoma who have received two or more lines of systemic therapy.

However, NICE said it isn’t clear how much of a benefit axicabtagene ciloleucel may provide over salvage chemotherapy. Additionally, the cost of axicabtagene ciloleucel is too high for it to be considered a cost-effective use of NHS resources, and the therapy does not meet criteria for inclusion in the Cancer Drugs Fund.

1. Borchmann P et al. AN UPDATED ANALYSIS OF JULIET, A GLOBAL PIVOTAL PHASE 2 TRIAL OF TISAGENLECLEUCEL IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL). EHA 2018. Abstract S799.