Background: The efficacy of nivolumab (Nivo) at a fixed dose of 40 mg in patients with relapsed and refractory classic Hodgkin lymphoma (r/r cHL) was demonstrated in previous studies. Nevertheless, comparison of the efficacy of low doses of PD1 inhibitors with standard dose 3 mg/kg is currently required.
Aims: To compare the results of Nivo 40 mg therapy versus standard dosing regimen of 3 mg/kg for patients with r/r cHL.
Methods: The Nivo40 trial (NCT03343665) expanded prospective cohort of patients (group 1, n=51) treated with Nivo 40 mg was compared with the retrospective group 2 (n=116) of patients treated with Nivo 3 mg/kg. The response was evaluated every 3 months by PET-CT using LYRIC criteria. Adverse events (AE) were analyzed by NCI CTCAE 4.0.3. Overall response rate (ORR), progression-free survival (PFS), overall survival (OS) were compared between group 1 and 2. During the survival analysis the PFS was censored by the time of additional therapy initiation.
Results: Patient's characteristics are demonstrated in the table 1. Median follow up was 48 (2-60) months in group 1 and 60 (6-70) months in group 2. Median Nivo cycles was 19 (2-49) and 20 (1-32) respectively. The best response to Nivo therapy was detected at 6 (2-24) and 6 (1-27) cycles respectively. ORR was 68% in group 1 and 67% in group 2. The structure of response in group 1 was: complete response (CR) in 40% of patients, partial response (PR) in 28%, stable disease (SD) in 6%, indeterminate response (IR) in 20% and progressive disease (PD) in 6%; in group 2: CR in 34%, PR in 33%, SD in 5%, IR in 20% and PD in 8%. Median OS was not achieved in both groups, 3-year OS was 97,9% and 96,5% respectively (p=0.243). Median PFS was 21,9 months (95%CI: 16,8-26,9) in group 1 and 18,8 months (95%CI: 13,4-24,2) in group 2, 3-year PFS was 23,6% and 27% respectively (p=0.356). Any grade AE were detected in 65% of patients in group 1 and in 79% in group 2 (p=0.068), 3-4 grade AE were detected in 10% and 19% respectively (p=0.151). Additional therapy after Nivo monotherapy was started in 78% of patients after Nivo 40 mg and in 84% after Nivo 3 mg/kg. Allogeneic stem cell transplantation after Nivo therapy was performed in 5 (10%) patients in group 1 and in 26 (22%) patients in group 2.
Conclusion: The efficacy of Nivo 40 mg therapy is comparable to the standard dose of 3 mg/kg in patients with r/r cHL. However, a direct comparison of different doses of Nivo in a prospective study is required.