Owen A. O’Connor, MD
A phase I/II trial has shown that the addition of brentuximab vedotin (Adcetris) to bendamustine is active in relapsed or refractory Hodgkin lymphoma. The study findings were reported in The Lancet Oncology by Owen A. O’Connor, MD, of the Center for Lymphoid Malignancies, Columbia University Medical Center, and colleagues.
In the study, 64 patients with Hodgkin lymphoma and 1 with anaplastic large T-cell lymphoma (28 in phase I, 37 in phase II) were enrolled between July 2012 and May 2017. In phase I, patients received 1 dose of either 1.2 or 1.8 mg/kg of brentuximab vedotin on day 1 of a 21-day cycle plus 1 dose of bendamustine at 70, 80, or 90 mg/m2 on days 1 and 2 of the cycle. In phase II, patients received the recommended phase II dose from phase I of 1.8 mg/kg of brentuximab vedotin and 90 mg/m2 of bendamustine.
All patients had biopsy--proven CD30-positive tumors and had received at least one previous multi-agent chemotherapy regimen. The median number of prior therapies was five in phase I and three in phase II.
No maximum tolerated dose of the combination was reached in phase I. Dose-limiting toxicities were observed in 3 of 28 patients (11%), including grade 4 neutropenia in 2 patients and diffuse rash in 1 patient. Objective response was observed in 17 patients (61%), including a complete response in 5 (18%), in phase I and in 29 of 37 patients (78%), including a complete response, in 16 (43%) in phase II. Median durations of response were 4.3 months in phase I and 3.95 months in phase II.
The most common grade 3 or 4 adverse events in phase I were anemia (18%), decreased platelet count (14%), neutropenia (11%), and infusion reaction (8%). Grade 3 or 4 adverse events in phase II consisted of neutropenia in 35% and lung infection in 14%. Adverse events led to discontinuation of treatment in two patients in phase I and two patients in phase II. No treatment-related deaths were observed.
The investigators concluded: “This study shows that brentuximab vedotin plus bendamustine, with a favourable safety profile, is an active salvage regimen for heavily pretreated patients with relapsed or refractory Hodgkin’s lymphoma. This salvage regimen can potentially serve as an efficacious and safe alternative to platinum-based chemotherapy before autologous stem cell transplant.” ■
