Brentuximab vedotin plus bendamustine: a highly active first salvage regimen for relapsed or refractory Hodgkin lymphoma

Abstract

Autologous stem cell transplantation (ASCT) is standard of care for patients with Hodgkin lymphoma (HL) who have relapsed/refractory disease after frontline chemotherapy. Achievement of complete remission (CR) with pre-ASCT salvage chemotherapy predicts favorable outcomes post-ASCT. This phase 1/2 study evaluated the combination of brentuximab vedotin (BV) plus bendamustine as a first salvage regimen in relapsed/refractory HL. A total of 55 patients (28 primary refractory and 27 relapsed) were enrolled. Patients received BV (1.8 mg/kg) on day 1 and bendamustine (90 mg/m²) on days 1 and 2 of a 21-day cycle for up to 6 cycles. Patients could undergo ASCT any time after cycle 2. Following ASCT or completion of combination therapy if not proceeding to ASCT, patients could receive BV monotherapy for up to 16 cycles of total therapy. After a median of 2 cycles of combination therapy (range, 1-6), the objective response rate among 53 efficacy-evaluable patients was 92.5%, with 39 patients (73.6%) achieving CR. Forty patients underwent ASCT. Thirty-one patients (25 of whom underwent ASCT) received BV monotherapy (median, 10 cycles; range, 1-14). After a median of 20.9 months of follow-up, the estimated 2-year progression-free survival was 69.8% and 62.6% for patients who received ASCT and all patients, respectively. Thirty-one patients (56.4%) experienced infusion-related reactions (IRRs), with a majority occurring during cycle 2 of combination therapy. A protocol amendment requiring premedication reduced IRR severity. BV plus bendamustine as first salvage therapy in relapsed/refractory HL is highly active with a manageable toxicity profile. This trial was registered at www.clinicaltrials.gov as #NCT01874054.

Graphical abstract

Figure 1.

Study design. CT, computed tomography; EOT, End-of-Treatment; PET, positron emission tomography.

Figure 2.

Patient disposition. Boxes highlighted in pink indicate best response to combination therapy among subpopulations of patients who did and did not proceed to ASCT. Efficacy-evaluable patients who discontinued treatment owing to AEs during combination therapy are indicated by dashed lines; patients who completed combination therapy but did not enroll in the brentuximab monotherapy phase are shown separately.

Figure 3.

Kaplan-Meier analyses. (A) Overall survival for all patients and for those who underwent ASCT. (B) Progression-free survival for all patients and for those who underwent ASCT. (C) Duration of complete remission according to ASCT status.

Figure 4.

Influence of premedication and ATA status on infusion-related reactions. (A) Incidence of IRRs by category (all IRRs and those reported as SAEs, grade 3/4, or leading to treatment discontinuation) among patients in the safety population (N = 55), according to whether the first dose of combination therapy was administered before or after a protocol amendment requiring premedication with antihistamines and corticosteroids. Inset, ATA incidence among immunogenicity-evaluable patients (N = 48) before and after the amendment. (B) ATA status of patients in each IRR category in the population of 54 patients with any ATA assessment (42 ATA⁺ at any time during the study and12 ATA⁻ throughout the study). IRR, infusion-related reaction; SAE, serious adverse event.