PET-ADAPTED NIVOLUMAB +/- ICE AS INITIAL SALVAGE THERAPY IN RELAPSED/REFRACTORY HODGKIN LYMPHOMA

Introduction: Nivolumab (nivo) is an anti-PD-1 antibody that restores effective anti-tumor immune responses and is tolerable and effective in patients (pts) with relapsed/refractory (RR) Hodgkin lymphoma (HL). Nivo combined with brentuximab vedotin (BV) as initial salvage therapy yields high response rates and favorable progression-free survival as a bridge to autologous stem cell transplantation (ASCT) in pts with RR HL. With the frontline approval of BV, it is necessary to evaluate the role of nivo as salvage therapy separate from BV. We report the preliminary results of a phase 2 trial evaluating PET-adapted nivo +/- ICE chemotherapy as initial salvage treatment in RR HL prior to ASCT. Methods: In this prospective, multicenter trial, pts with biopsy-proven RR HL after frontline therapy received 3 mg/kg nivo every 2 weeks for up to 6 cycles. PET-CT was performed after cycle 3 and cycle 6. After cycle 6, pts in CR proceeded to ASCT while pts not in CR received nivo + ICE (NICE) for 2 cycles. The primary endpoint was complete response rate according to 2014 Lugano classification. Results: 28 pts were evaluable for toxicity; 26 were evaluable for response. 68% were male, median age 35 years, 46% were primary refractory; at baseline, 50% had stage III-IV, 43% had B symptoms, and 68% had bulky disease (> 5cm). 22 pts received nivo alone and 6 pts received nivo/NICE. 25 pts completed therapy, 1 pt discontinued early in CR to undergo ASCT, 2 pts discontinued nivo early due to adverse events (AE, 1 pt = Gr 4 altered mental status, 1 pt = Gr 2 pneumonitis). Nivo-related AEs were consistent with known AE profile, rash (21%, all grade 1) was the most common AE and only 1 pt had grade 3-4 AEs (1 HIV+ pt with Gr 4 altered mental status and Gr 3 tumor lysis syndrome). In pts who received NICE, the most common AEs were nausea and vomiting (50%, all Gr 1) and the only Gr 3-4 event was Gr 4 neutropenia in one pt. 25 out of 26 evaluable pts (96%) responded to nivo, with a best CR rate of 81% (21/26). 3 pts who initially responded to nivo (1 CR, 2 PR) had progressive disease at the end of 6 cycles. At the end of nivo, the CR rate was 77% (20/26) and overall response rate was 85% (22/26). 6 pts were treated with NICE and 5 achieved CR (83%). Overall, at the end of protocol therapy (nivo or nivo/NICE), 96% (25/26) of evaluable pts were in CR. 22 pts proceeded to ASCT directly after protocol therapy and 3 pts in CR refused ASCT. One pt with PR after NICE subsequently responded to additional salvage therapy and is proceeding to ASCT. In pts who proceeded to ASCT, a median of 2 stem cell collections were required, a median of 4.8x106 CD34+ cells/kg (range 3.12 – 16.23) were collected, and the median time to neutrophil and platelet engraftment were 11 and 13 days, respectively. All transplanted pts remain in CR with median follow-up time of 5 months (range, 0-19mo). Conclusion: PET-adapted Nivo followed by NICE is a well-tolerated and highly effective first salvage regimen in pts with RR HL that merits further exploration. AFH and RC contributed equally Keywords: Hodgkin lymphoma (HL); ICE; nivolumab. Disclosures: Herrera, A: Consultant Advisory Role: Bristol-Myers Squibb, Genentech, Merck, Adaptive Biotechnologies and Kite Pharma/Gilead; Research Funding: Bristol-Myers Squibb, Genentech, Immune Design, AstraZeneca, Merck, Seattle Genetics and Kite Pharma, Gilead Sciences.