Brentuximab Vedotin in Combination with Bendamustine for Patients with Hodgkin Lymphoma who are Relapsed or Refractory after Frontline Therapy

• Published in: Blood 2014-12, Vol.124 (21), p.293-293
• Main Authors: LaCasce, Ann, Bociek, R. Gregory, Matous, Jeffrey, Sawas, Ahmed, Caimi, Paolo, Ansell, Stephen M., Islas-Ohlmayer, Miguel, Cheung, Eric, Agura, Edward, Behler, Caroline, Crosswell, Howland, Vose, Julie M., Josephson, Neil, Advani, Ranjana
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V124.21.293.293

▪ Background Patients (pts) with Hodgkin lymphoma (HL) who have relapsed/refractory disease after frontline therapy typically undergo salvage chemotherapy followed by high-dose conditioning and autologous stem cell transplant (ASCT). Improved outcomes have been reported for pts who achieve complete remission (CR) with salvage chemotherapy prior to ASCT. Variable CR rates (19%-60%) and significant toxicities are associated with standard salvage therapy in the first relapse setting. Brentuximab vedotin and bendamustine have independent mechanisms of action and are highly active with manageable safety profiles when administered as single agents to pts with HL who relapse after ASCT (brentuximab vedotin: 34% CR [Younes, 2012]; bendamustine: 33% CR [Moskowitz, 2013]). This phase 1/2, single-arm, 2-stage, open-label study was designed to evaluate the safety and efficacy of brentuximab vedotin in combination with bendamustine for the treatment of pts with HL in first relapse (ClinicalTrials.gov #NCT01874054). Methods Pts received an outpatient IV infusion of 1.8 mg/kg brentuximab vedotin on Day 1 with 90 mg/m2 bendamustine on Days 1 and 2 of 3-week cycles for up to 6 cycles. Pts could undergo ASCT any time after Cycle (C) 2 and post-transplant resume treatment with brentuximab vedotin as monotherapy for up to16 total doses. Phase 1 was designed to determine the recommended dose of bendamustine in combination with brentuximab vedotin. During this phase, the dose of bendamustine was to be de-escalated if ≥4/10 pts experienced dose-limiting toxicity (DLT), defined as any C1 toxicity requiring a dose delay of ≥14 days. During phase 2, bendamustine was administered at the recommended dose in order to assess the CR rate of the combination. Response was assessed by the investigator per Cheson 2007. Results Forty-five pts (58% female) with a median age of 35 yrs (range, 19-79) have been enrolled. Fifty-eight percent of pts had relapsed disease and 42% of pts primary refractory disease after frontline therapy. A median of 13.1 mos (range, 3- 98) had elapsed since initial diagnosis. No DLTs were observed in the safety cohort, thus the recommended dose of bendamustine in combination with brentuximab vedotin was 90 mg/m2. Pts received a median of 2 cycles (range, 1-6) of the combination. The main toxicity observed with the combination was infusion-related reactions. The most common symptoms (≥10%) were dyspnea (13%), flushing (13%), and chills (11%). The majority of reaction