Conventional salvage therapy for patients (pts) with relapsed/refractory (R/R) Hodgkin lymphoma (HL) is associated with variable complete remission (CR) rates (19%-60%) and substantial toxicity. Brentuximab vedotin (BV) and bendamustine are active as single agents in pts with R/R HL (34% and 33% CR rates, respectively), with manageable safety profiles. This phase 1/2 open-label study was designed to evaluate the safety and efficacy of BV in combination with bendamustine in pts with primary refractory disease or in first relapse (NCT01874054). Pts received BV (1.8 mg/kg on Day 1) plus bendamustine (90 mg/m^2 on Days 1 and 2) in 3-week cycles (up to 6 cycles total). Pts could undergo autologous stem cell transplant (ASCT) any time after Cycle 2 and could receive BV monotherapy (up to 16 total doses) post-ASCT, or after completion of combination therapy if not proceeding to ASCT. Response was assessed by the investigator per Cheson 2007. A total of 55 pts (51% refractory; 49% relapsed) were enrolled. Median age was 36 years (range 19-79), 56% were female, and median time from HL diagnosis was 14 months (range 3-98). Pts received a median of 2 cycles (range 1-6) of the combination and 11 cycles (range 1-14) of BV monotherapy. Infusion-related reactions (IRRs) were reported in 58% of pts; however, a protocol amendment requiring premedication with corticosteroids and antihistamines during combination therapy reduced the IRR-related discontinuation rate from 24% (6/25 pts) to 7% (2/30 pts). Common IRR symptoms (≥10%) were pyrexia (26%), chills (20%), dyspnea (16%), nausea and flushing (15% each), and hypotension and pruritus (11% each). The CR rate of the combination was 74% (39/53 pts evaluable for response); objective response rate (CR and partial remission) was 93% (49/53 pts). Stem cell mobilization succeeded with 1st-line agents in 39/41 pts (95%); median yield was 4.2x10^6 CD34+ cells/kg. Median follow-up was 19 months (range 1-33). To date, 17 progression events have occurred in 53 pts: 11 in 40 pts who underwent ASCT and 6 in 13 pts who did not. The estimated 24-month progression-free survival was 68% for the ASCT population (95% CI: 48%, 82%) and 61% for the overall population (95% CI: 44%, 75%). Of 3 deaths, 2 were attributed to HL progression and 1 to septic shock after ASCT. Overall, these data demonstrate that the outpatient regimen of BV plus bendamustine is an active salvage therapy for pts with HL in first relapse and can be used prior to ASCT.