In the Journals

Brentuximab vedotin data ‘practice changing’ for older patients with Hodgkin lymphoma

Brentuximab vedotin administered sequentially before and after standard chemotherapy appeared effective and safe for older patients with previously untreated Hodgkin lymphoma, according to results of a multicenter, phase 2 study.

Also, geriatric-based measures were strongly associated with patient survival.

“Historically, survival rates for older patients with Hodgkin lymphoma, typically defined as 60 years and older, have been shown to be disproportionately and markedly inferior compared with younger patients. Compounding this has been the underrepresentation of older Hodgkin lymphoma patients in clinical trials over the past several decades,” Andrew M. Evens, DO, MSc, associate director for clinical services and director of the Lymphoma Program at Rutgers Cancer Institute of New Jersey, said in a press release. “In this current study, the survival rates are among the best reported compared with prior Hodgkin lymphoma studies.”

Evens and colleagues assessed the safety and efficacy of brentuximab vedotin (Adcetris, Seattle Genetics) before and after standard chemotherapy — which consists of doxorubicin, vinblastine and dacarbazine (AVD) — among older patients with previously untreated Hodgkin lymphoma.

The analysis included 48 patients aged 60 years or older (median age, 69 years; range, 60-88; 63% men). Median ECOG performance status was 1, and 81% of patients had stage III to stage IV disease.

The median Cumulative Illness Rating Scale-Geriatric comorbidity score was 7, and 12% of the patients had loss of instrumental daily living activities at diagnosis.

Patients received two lead-in doses of single-agent brentuximab vedotin (1.8 mg/kg every 3 weeks) in combination with six cycles of AVD chemotherapy. Responding patients then received four consolidative doses of brentuximab vedotin.

The complete remission rate served as the primary endpoint. Objective response rate, prognostic relevance of PET and CT scans, safety, and 2-year PFS and OS rates served as secondary endpoints.

Results showed an ORR of 82% and complete remission rate of 36% among the first 22 evaluable patients after the initial lead-in dose of brentuximab vedotin. After six cycles of AVD, ORR increased to 95% and complete remission rate to 90% among 42 response-evaluable patients.

After median follow-up of 23 months (range, 2-49), researchers reported a 2-year EFS rate in the intent-to-treat population of 80% (95% CI, 65-89), PFS of 84% (95% CI, 69-92), and OS of 93% (95% CI, 80-98).

Moreover, 2-year PFS was 45% for patients with a Cumulative Illness Rating Scale-Geriatric comorbidity score of 10 or higher compared with 100% for those with a score of less than 10 (P < .001). Also, fewer patients with baseline loss of instrumental daily living activities achieved 2-year PFS (25% vs. 94%; P < .001).

Forty-two percent of patients experienced a serious adverse event.

The most common grade 3 or grade 4 adverse events included neutropenia (44%), febrile neutropenia and pneumonia (8%), or diarrhea (6%). One patient died of treatment-related pancreatitis and two patients died of progressive disease.

“Overall, therapy was well tolerated when compared with other analyses studying similar patients. These data will be practice-changing for our field,” Evens said in the release. “Next steps are to continue to maintain these robust remission and survival rates with less chemotherapy for older Hodgkin lymphoma patients.” – by Jennifer Southall

Disclosures: Evens reports consultant/advisory roles with Afmed Therapeutics, Celgene, Kite Pharma, Merck, Millennium Pharmaceuticals, Pharmacyclics, Seattle Genetics and Spectrum Pharmaceuticals; and research funding from 3-V Biosciences, Celgene, Innity Pharmaceuticals, Millennium Pharmaceuticals and TESARO. Please see the study for all other authors’ relevant financial disclosures.

Brentuximab vedotin administered sequentially before and after standard chemotherapy appeared effective and safe for older patients with previously untreated Hodgkin lymphoma, according to results of a multicenter, phase 2 study.

Also, geriatric-based measures were strongly associated with patient survival.

“Historically, survival rates for older patients with Hodgkin lymphoma, typically defined as 60 years and older, have been shown to be disproportionately and markedly inferior compared with younger patients. Compounding this has been the underrepresentation of older Hodgkin lymphoma patients in clinical trials over the past several decades,” Andrew M. Evens, DO, MSc, associate director for clinical services and director of the Lymphoma Program at Rutgers Cancer Institute of New Jersey, said in a press release. “In this current study, the survival rates are among the best reported compared with prior Hodgkin lymphoma studies.”

Evens and colleagues assessed the safety and efficacy of brentuximab vedotin (Adcetris, Seattle Genetics) before and after standard chemotherapy — which consists of doxorubicin, vinblastine and dacarbazine (AVD) — among older patients with previously untreated Hodgkin lymphoma.

The analysis included 48 patients aged 60 years or older (median age, 69 years; range, 60-88; 63% men). Median ECOG performance status was 1, and 81% of patients had stage III to stage IV disease.

The median Cumulative Illness Rating Scale-Geriatric comorbidity score was 7, and 12% of the patients had loss of instrumental daily living activities at diagnosis.

Patients received two lead-in doses of single-agent brentuximab vedotin (1.8 mg/kg every 3 weeks) in combination with six cycles of AVD chemotherapy. Responding patients then received four consolidative doses of brentuximab vedotin.

The complete remission rate served as the primary endpoint. Objective response rate, prognostic relevance of PET and CT scans, safety, and 2-year PFS and OS rates served as secondary endpoints.

Results showed an ORR of 82% and complete remission rate of 36% among the first 22 evaluable patients after the initial lead-in dose of brentuximab vedotin. After six cycles of AVD, ORR increased to 95% and complete remission rate to 90% among 42 response-evaluable patients.

After median follow-up of 23 months (range, 2-49), researchers reported a 2-year EFS rate in the intent-to-treat population of 80% (95% CI, 65-89), PFS of 84% (95% CI, 69-92), and OS of 93% (95% CI, 80-98).

Moreover, 2-year PFS was 45% for patients with a Cumulative Illness Rating Scale-Geriatric comorbidity score of 10 or higher compared with 100% for those with a score of less than 10 (P < .001). Also, fewer patients with baseline loss of instrumental daily living activities achieved 2-year PFS (25% vs. 94%; P < .001).

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Forty-two percent of patients experienced a serious adverse event.

The most common grade 3 or grade 4 adverse events included neutropenia (44%), febrile neutropenia and pneumonia (8%), or diarrhea (6%). One patient died of treatment-related pancreatitis and two patients died of progressive disease.

“Overall, therapy was well tolerated when compared with other analyses studying similar patients. These data will be practice-changing for our field,” Evens said in the release. “Next steps are to continue to maintain these robust remission and survival rates with less chemotherapy for older Hodgkin lymphoma patients.” – by Jennifer Southall

Disclosures: Evens reports consultant/advisory roles with Afmed Therapeutics, Celgene, Kite Pharma, Merck, Millennium Pharmaceuticals, Pharmacyclics, Seattle Genetics and Spectrum Pharmaceuticals; and research funding from 3-V Biosciences, Celgene, Innity Pharmaceuticals, Millennium Pharmaceuticals and TESARO. Please see the study for all other authors’ relevant financial disclosures.