Response-adapted anti-PD-1–based salvage therapy for Hodgkin lymphoma with nivolumab alone or in combination with ICE

Abstract

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

Updates in the Role of Checkpoint Inhibitor Immunotherapy in Classical Hodgkin’s Lymphoma

“…On the other hand, the investigation of anti-PD-1 mAb in the first relapse in several phase II studies has demonstrated increased depth of response both as a single agent and as combination therapy ( Table 1 ) [ 33 , 34 , 35 ]. Combination BV and Nivo demonstrated ORR of 82–85% and CR of 59–67% [ 32 , 69 , 70 ] At 3 year follow-up after combination achieved a PFS of 77%, and in patients who responded to induction and proceeded to ASCT, PFS improved to 91% [ 33 ].…”

“…In a small phase II PET-adapted study evaluating nivolumab monotherapy followed by escalation to nivolumab with ifosfamide, carboplatin, and etoposide (ICE) in patients with positive interim PET scans, 71% of patients achieved CR to the single agent nivolumab and were eligible to proceed directly to ASCT, sparing 26 of the total 42 evaluable patients from requiring cytotoxic treatments prior to ASCT. A total of 9 of the 42 patients required escalation of their treatment to N-ICE, and of these, 89% achieved CR [ 35 ]. This approach demonstrated overall 2 year PFS and OS of 72% and 95%, respectively ( Table 1 ) [ 35 ].…”

“…A total of 9 of the 42 patients required escalation of their treatment to N-ICE, and of these, 89% achieved CR [ 35 ]. This approach demonstrated overall 2 year PFS and OS of 72% and 95%, respectively ( Table 1 ) [ 35 ]. Larger studies are underway to evaluate nivolumab monotherapy as salvage prior to ASCT ( Table 2 ).…”

Autologous Stem Cell Transplantation in Hodgkin Lymphoma—Latest Advances in the Era of Novel Therapies

“…Thus, most of the patients were able to proceed to autoHCT with nivo alone. The remaining seven patients received NICE, and 100% responded, with six patients achieving a CR (86%) and 1 PR (14%); 33 patients proceeded to autoHCT directly after protocol therapy, and the 2-year post-autoHCT OS and PFS were 97% and 94%, respectively [ 36 ].…”

“…For instance, 5-year follow-up of BV monotherapy found that 9% of patients achieved a long-term remission exceeding 5 years with no further therapy [ 27 ]. In the case of the CPI, both nivo and pembro were found to have 5-year PFS under 20% [ 38 , 39 ]; of the four patients who achieved CR with nivo in the nivo + ICE trial who refused autoHCT, three had relapsed [ 36 ].…”