Brentuximab Vedotin Plus Gemcitabine in Pediatric and Young Adult Patients With Relapsed/Refractory Hodgkin Lymphoma
In a Children’s Oncology Group phase I/II trial reported in The Lancet Oncology, Cole et al found that the combination of brentuximab vedotin (Adcetris) and gemcitabine was active in pediatric and young adult patients with relapsed or refractory Hodgkin lymphoma. As noted by the investigators, preclinical data indicate that brentuximab vedotin can sensitize lymphoma cells to gemcitabine.
The study included 45 patients aged < 30 years enrolled between February 2013 and August 2016 from sites in the United States and Canada who had no previous brentuximab vedotin exposure and had primary refractory disease or relapse within 1 year from completion of initial treatment. Treatment consisted of gemcitabine at 1,000 mg/m2 on days 1 and 8, and brentuximab vedotin at 1.4 mg/kg or 1.8 mg/kg on day 1 in 21-day cycles. The primary objectives included establishing the recommended phase II dose of brentuximab vedotin in the combination and the proportion of patients achieving complete response at the selected phase II dose within 4 cycles of treatment.
Response Rates and Adverse Events
The recommended phase II dose of brentuximab vedotin was 1.8 mg/kg in combination with gemcitabine at 1,000 mg/m2. Among 42 evaluable patients, 24 (57%, 95% confidence interval [CI] = 41%–72%) treated at this dose achieved a complete response within 4 cycles of treatment.
Among 13 patients with a partial response or stable disease, 4 (31%) had Deauville scores ≤ 3 in all target lesions. On modern response criteria, these 4 patients also had a complete response, yielding a complete response rate of 67% (28 of 42 patients; 95% CI = 51%–80%) with inclusion of these patients.
The most common grade 3 or 4 adverse events in 42 patients receiving the recommended phase II dose were neutropenia (36%), rash (36%), elevated transaminases (21%), and pruritus (10%). No treatment-related deaths were observed.
The investigators concluded, “Brentuximab vedotin with gemcitabine is a safe combination treatment with a tolerable toxicity profile for patients with primary refractory Hodgkin’s lymphoma or high-risk relapse. The preliminary activity of this combination shown in this trial warrants further investigation in randomised controlled trials.”
The study was funded by the National Institutes of Health and St. Baldrick's Foundation.
Peter D. Cole, MD, of The Children’s Hospital at Montefiore, is the corresponding author for The Lancet Oncology article.
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