Brentuximab vedotin achieves durable clinical response in Hodgkin lymphoma.
Major finding: Brentuximab vedotin achieves durable clinical response in Hodgkin lymphoma.
Approach: A phase II study evaluated safety and efficacy in relapsed or refractory Hodgkin lymphoma.
Impact: Patients with earlier-stage disease may also benefit from brentuximab vedotin.
Patients with Hodgkin lymphoma who relapse after autologous stem cell transplantation (SCT) have a very poor prognosis. Because CD30 is expressed on malignant Hodgkin lymphoma cells, phase I studies have investigated the use of the antibody–drug conjugate brentuximab vedotin, which delivers the antimicrotubule agent monomethyl auristatin E into CD30-expressing cells, in patients with relapsed or refractory Hodgkin lymphoma. The high objective response rates observed prompted Younes and colleagues to conduct an open-label, phase II study further evaluating the safety and efficacy of brentuximab vedotin in 102 patients with relapsed or refractory Hodgkin lymphoma after autologous SCT. The authors observed an overall objective response rate of 75%, with 34% of patients achieving a complete response. For all patients included in the study, the median progression-free survival was 5.6 months. Significantly, for patients who achieved a complete response, the median progression-free survival and duration of response were 21.7 and 20.5 months, respectively, and 31 patients were still alive without evidence of disease progression at the time of the most recent follow-up. Peripheral neuropathy was the most clinically relevant adverse event and was mostly reversible after treatment discontinuation or dose reduction. Together, these findings are especially notable given that this cohort of patients had failed a median of 3.5 prior chemotherapy regimens and the majority had relapsed within a year of autologous SCT. As a result, brentuximab vedotin was granted accelerated approval by the U.S. Food and Drug Administration for refractory Hodgkin lymphoma in August 2011. Additional studies investigating the clinical response to this agent in patients with earlier-stage Hodgkin lymphoma are in progress.
Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol 2012 Mar 26 [Epub ahead of print].
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