The efficacy and safety of nivolumab 40 mg therapy versus 3 mg/kg in patients with relapsed and refractory classic Hodgkin lymphoma
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.
To compare the results of Nivo 40 mg therapy versus standard dosing regimen of 3 mg/kg for patients with r/r cHL.
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.
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.
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.