Autologous Stem Cell Transplantation After Second Line Brentuximab Vedotin in Relapsed or Refractory Hodgkin Lymphoma

Abstract

Background: We previously demonstrated that brentuximab vedotin (BV) used as second-line therapy in patients with Hodgkin lymphoma is a tolerable and effective bridge to autologous hematopoietic cell transplantation (AHCT). Here we report the post-AHCT outcomes of patients treated with second-line standard/fixed-dose BV and an additional cohort of patients where positron-emission tomography (PET) adapted dose-escalation of second-line BV was utilized. Patients and Methods: Patients on the dose-escalation cohort received 1.8 mg/kg of BV intravenously every 3 weeks for 2 cycles. Patients in complete remission (CR) after 2 cycles received 2 additional cycles of BV at 1.8 mg/kg, while patients with stable disease or partial response were escalated to 2.4 mg/kg for 2 cycles. All patients, regardless of treatment cohort, proceeded directly to AHCT or received additional pre-AHCT therapy at the discretion of the treating physician based on remission status after second-line BV.Results: Of the 20 patients enrolled to the BV dose-escalation cohort, 8 patients underwent BV dose-escalation. BV escalation was well-tolerated, but no patients who were escalated converted to CR. Of 56 evaluable patients treated across cohorts, the ORR to second-line BV was 77% with 43% CR. Twenty-seven (48%) patients proceeded directly to AHCT after BV alone, and a total of 50 patients proceeded to AHCT. Thirteen patients received consolidative post-AHCT therapy with either radiation, BV, or a PD-1 inhibitor. After AHCT, the 2-year progression-free survival (PFS) and overall survival were 67% and 93%, respectively. The 2-year PFS among patients in CR at the time of AHCT (n=37) was 71% compared to 54% in patients not in CR (p=0.12). The 2-year PFS in patients who proceeded to AHCT directly after receiving BV alone was 77%.Conclusions: Second-line BV is an effective bridge to AHCT that produces responses of sufficient depth to provide durable remission in conjunction with AHCT. (clinicaltrials.gov: NCT01393717)