Results of a Multicenter Phase II Trial of Brentuximab Vedotin as Second-Line Therapy before Autologous Transplantation in Relapsed/Refractory Hodgkin Lymphoma

Abstract

This multicenter prospective phase II study examines the activity and tolerability of brentuximab vedotin as second-line therapy in patients with Hodgkin lymphoma that was relapsed or refractory after induction therapy. Brentuximab vedotin (1.8 mg/kg) was administered i.v. on day 1 of a 21-day cycle for a total of 4 cycles. Patients then proceeded to autologous hematopoietic cell transplantation (AHCT), if eligible, with or without additional salvage therapy, based on remission status after brentuximab vedotin. The primary endpoint was overall response rate (ORR). Secondary endpoints were safety, stem cell mobilization/collection, AHCT outcomes, and association of CD68(+) with outcomes. Of 37 patients, the ORR was 68% (13 complete remission, 12 partial remission). The regimen was well tolerated with few grade 3/4 adverse events, including lymphopenia (1), neutropenia (3), rash (2), and hyperuricemia (1). Thirty-two patients (86%) were able to proceed to AHCT, with 24 patients (65%) in complete remission at time of AHCT. Thirteen patients in complete remission, 4 in partial remission, and 1 with stable disease (49%) received AHCT without salvage combination chemotherapy. CD68 expression did not correlate with response to brentuximab vedotin. The median number of stem cells mobilized was 6.0 × 10(6) (range, 2.6 to 34), and median number of days to obtain minimum collection (2 × 10(6)) was 2 (range, 1 to 6). Brentuximab vedotin as second-line therapy is active, well tolerated, and allows adequate stem cell collection and engraftment. For Hodgkin lymphoma patients with relapsed/refractory disease after induction therapy, second-line brentuximab vedotin, followed by combination chemotherapy for residual disease, can effectively bridge patients to AHCT.

Trial registration: ClinicalTrials.gov NCT01393717.

Keywords: Autologous hematopoietic transplantation; Brentuximab vedotin; Hodgkin lymphoma; Salvage.

Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. Study Schema

Patients with relapsed/refractory HL were treated with brentuximab vedotin 1.8 mg/kg intravenously every 3 weeks for maximum of 4 cycles. Radiographic assessment was done at the end of cycle 2 with CT or CT/PET scan. Patients were allowed to continue study if they achieved CR/PR/SD after 2 cycles. Radiographic assessment at end of study was done with CT/PET scan. Patients who achieved CR went directly to AHCT. Patients who achieved PR had the option of going directly to AHCT or receiving other salvage chemotherapy by investigators choice. *XRT denotes local radiation therapy.