Response-adapted anti-PD1 based salvage therapy for Hodgkin lymphoma with nivolumab +/- ICE (NICE)

This phase 2 trial evaluated PET-adapted nivolumab (Nivo) alone or in combination with ifosfamide, carboplatin, and etoposide (NICE) as first salvage therapy and bridge to autologous hematopoietic cell transplantation (AHCT) in relapsed/refractory (RR) classical Hodgkin lymphoma (cHL). Patients with RR cHL received 240mg Nivo every 2 weeks for up to 6 cycles (C). Patients in complete response (CR) after C6 proceeded to AHCT, while patients with progressive disease (PD) at any point or not in CR after C6 received NICE for 2 cycles. The primary endpoint was CR rate per the 2014 Lugano classification at completion of protocol therapy. 43 patients were evaluable for toxicity; 42 were evaluable for response. 34 patients received Nivo alone and 9 patients received Nivo+NICE. No unexpected toxicities were observed after Nivo or NICE. After Nivo, the overall response rate (ORR) was 81% and the CR rate was 71%. Among the 9 patients who received NICE, all responded with 8 (89%) achieving CR. At the end of all protocol therapy, the ORR and CR rates were 93% and 91%. Thirty-three patients were bridged directly to AHCT, including 26 after Nivo alone. The 2-year progression-free survival (PFS) and overall survival in all treated patients (n=43) were 72% (95%CI:56-83) and 95% (95%CI:82-99), respectively. Among the 33 patients who bridged directly to AHCT after protocol therapy, the 2-year PFS was 94% (95%CI:78-98). PET-adapted sequential salvage therapy with Nivo or Nivo+NICE was well-tolerated and effective, resulting in a high CR rate and bridging most patients to AHCT without chemotherapy. This Clinical Trial is registered under NCT03016871