ASH 2014: Post-Transplant Brentuximab Vedotin Improves Progression-Free Survival in Hodgkin Lymphoma Patients
In Hodgkin lymphoma patients at risk for disease progression following autologous stem cell transplant, early consolidation post-transplant with brentuximab vedotin (Adcetris) significantly improved progression-free survival compared with placebo in the phase III AETHERA trial. The findings were presented at a press conference during the 56th American Society of Hematology Annual Meeting and Exposition (Abstract 673).
Median progression-free survival was 43 months for the brentuximab vedotin–treated group vs 24 months for placebo, representing a significant 43% reduction in risk of disease progression (P = .001).
Potential New Standard of Care
“In my opinion, once this study is published, brentuximab vedotin should be the standard of care for patients with the characteristics in this trial. That is, remission duration < 1 year, disease outside of the lymph nodes, B symptoms, two or more prior salvage therapies, and primary refractory disease,” said lead author Craig Moskowitz, MD, Clinical Director of the Division of Hematologic Oncology at Memorial Sloan Kettering Cancer Center, New York.
Dr. Moskowitz explained that autologous stem cell transplant can achieve cure in approximately 50% of patients with relapsed/refractory Hodgkin lymphoma. Over the past 2 decades, no stem cell transplant regimen for aggressive lymphoma has improved outcomes further. About 50% of patients will relapse after stem cell transplant, reflecting the need for better treatments.
Brentuximab is an antibody drug conjugate directed to CD30, which is expressed almost universally in Reed-Sternberg cells (classical lymphoma cells). The drug is FDA-approved for relapsed/refractory Hodgkin lymphoma and for systemic anaplastic large cell lymphoma, but not as post-transplant consolidation.
“AETHERA is the only placebo-controlled randomized study ever done in Hodgkin lymphoma to compare brentuximab vedotin vs placebo in patients at risk for disease progression after autologous stem cell transplant,” Dr. Moskowitz said.
AETHERA Trial
The multicenter trial was conducted at 78 sites in the United States, Europe, and Russia. A total of 329 Hodgkin lymphoma patients at risk of relapse were randomly assigned to 16 cycles of treatment with brentuximab vedotin or placebo. Patients who relapsed on placebo were allowed to crossover to the brentuximab vedotin arm. Nearly 50% of patients had three or more risk factors for disease progression.
Two-year progression-free survival as assessed by investigator was 65% vs 45%, respectively. “A 20% difference in progression-free survival has never been seen in refractory lymphoma before, let alone in Hodgkin lymphoma,” Dr. Moskowitz said.
The progression-free survival benefit was consistent across all prespecified subgroups, including primary refractory patients who relapsed within 12 months of front-line therapy and patients who relapsed after 12 months with extranodal disease.
At the interim analysis, overall survival was similar in both groups at 2 years. Dr. Moskowitz attributed this to the large percentage of patients who crossed over to active treatment from the placebo arm (85%). The final overall survival analysis is expected in 2016.
In the brentuximab vedotin arm, peripheral sensory neuropathy was the most common adverse event (56%), followed by neutropenia (35%), upper respiratory tract infection (26%), fatigue (24%), and peripheral motor neuropathy (23%). With dose reductions, peripheral sensory neuropathy resolved in 85% of patients on the brentuximab vedotin arm.
Dr. Moskowitz reported research funding from Genentech, Merck, and Seattle Genetics, and consultancy with Seattle Genetics. For full disclosures of the study authors, view the study abstract.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
