Cole PD, et al. - In children and young adults with primary refractory Hodgkin's lymphoma or early relapse, authors assessed the safety and effectiveness of brentuximab vedotin with gemcitabine. Findings suggested a safety of brentuximab vedotin with gemcitabine as combination treatment with a tolerable toxicity profile for patients with primary refractory Hodgkin's lymphoma or high-risk relapse.

Methods

• Experts in this Children's Oncology Group, multicenter, single-arm, phase 1-2 trial recruited patients with Hodgkin's lymphoma from hospitals across the US and Canada.
• Patients eligible for this trial were younger than 30 years old, had no previous brentuximab vedotin exposure, and had primary refractory disease or relapse of less than 1 year from completion of initial treatment.
• Each 21-day cycle consisted of 1,000 mg/m² intravenous gemcitabine on days 1 and 8 and intravenous brentuximab vedotin on day 1 at 1.4 mg/kg or 1.8 mg/kg.
• To establish the recommended phase 2 dose of brentuximab vedotin in this combination, the safety of the combination, and the proportion of patients who achieved a complete response among those treated at the recommended phase 2 level within four cycles of treatment were included in the primary objectives.

Results

• In the two phases of the study, 46 patients were enrolled, including one who was deemed ineligible, between February 5, 2013 and August 19, 2016.
• Findings suggested that the recommended phase 2 dose of brentuximab vedotin was 1.8 mg/kg in combination with gemcitabine 1,000 mg/m^2.
• A complete response within the first four cycles of treatment was demonstrated by 24 (57%) of 42 evaluable patients (95% CI 41–72) at this dose level.
• All target lesions with Deauville scores of 3 or less after cycle 4 were seen in 4 (31%) of 13 patients with a partial response or stable disease.
• Results demonstrated that, by modern response criteria, these were also complete responses (total number with complete response 28 [67%] of 42 [95% CI 51–80]).
• Neutropenia (15 [36%]), rash (15 [36%]), transaminitis (9 [21%]), and pruritus (4 [10%]) were the most common grade 3–4 adverse events in all 42 participants treated at the recommended phase 2 dose.
• No treatment-related deaths were noted.