Phase 2 trial of brentuximab vedotin and gemcitabine for pediatric and young adult patients with relapsed or refractory Hodgkin lymphoma (HL): A Children’s Oncology Group (COG) report.

Abstract

7527 Background: AHOD1221 (NCT01780662) tested Brentuximab vedotin (Bv) with gemcitabine (GEM) in children or young adults with HL. The primary objective was to describe the complete response (CR) rate within 4 cycles of therapy. Methods: Eligibility criteria included age ≤30 years; no prior Bv exposure; and primary refractory HL or advanced stage disease with early relapse. Each 21-day cycle consisted of Bv on day 1 at the recommended phase 2 dose (RP2D), 1.8 mg/kg and GEM 1000mg/m2 on days 1 and 8. Patients were evaluable for response if they completed 4 cycles of Bv+GEM, had a CR after 2 cycles, or progressive disease at any time. Response was assessed after even cycles, and confirmed by central review. CR was defined by FDG-PET negativity (Deauville 1-2) regardless of residual lesion size. Results: 42 patients were treated with Bv+GEM. Median age was 17.4 years (range 5.4-28.7), and 23 (55%) were female. The majority (n=35; 83%) had primary refractory disease or early relapse <6 months after completion of primary treatment. Common (>10%) adverse events included maculopapular rash (36% in cycle 1), neutropenia (33%) and elevated serum transaminases (21%). GCSF-stimulated peripheral blood stem cell (PBSC) collection was successful in all patients (n=23) for whom it was attempted, with median total collection of 9.4x106CD34+ cells/kg (range 3.5-36.8). 23 of 40 evaluable patients experienced a CR (58%; 95% CI 42-73%) within four cycles, and 6 had a partial response (PR), for an ORR of 73% (95% CI, 59-86%). For 4 patients with PR or stable disease, all target lesions were Deauville 3 or less after cycle 4, considered a CR by modern response criteria (Cheson et al. Blood 2016;128(21): 2489). Conclusions: Bv+GEM is a highly active combination for primary refractory or high-risk relapse of HL, with a CR rate exceeding that seen after either Bv (34%) or GEM (9%) alone. PBSCs can be collected successfully following Bv+GEM, making this an effective reinduction regimen when autologous stem cell transplantation is indicated. Compared to alternate retrieval regimens, Bv+GEM offers the advantage of avoiding agents associated with late treatment sequelae. Clinical trial information: NCT01780662.