Background: The optimal nivolumab (N) therapy duration for patients (pts) with relapsed and refractory classic Hodgkin lymphoma (r/r cHL) has not been determined and this question remains a pressing issue. The possibility of prolonged remission after treatment discontinuation in complete response (CR) as well as the preservation of sensitivity to PD-1 inhibitors retreatment was previously demonstrated. However as the number of report regarding the problem of N discontinuation and retreatment is limited, the accumulation of additional data is required.
Aims: To analyze the survival of pts with r/r cHL after N discontinuation as well as the efficacy and safety of N retreatment.
Methods: The retrospective analysis included 48 pts with r/r cHL who were treated with N 3 mg/kg (n=29) or 40 mg (n=19). All pts discontinued N due to different reasons in CR (n=40) or partial response (PR) (n=8). In case of disease relapse the PD-1 inhibitors monotherapy was reinitiated. The response was evaluated by PET-CT using LYRIC criteria. Adverse events (AE) were analyzed by NCI CTCAE 4.0.3. In group of N discontinuation PFS, OS were evaluated. In group of N retreatment ORR, PFS, OS and AE rate were also analyzed. PFS estimates was censored by the time of additional therapy initiation in group of N retreatment.
Results: Patient’s characteristics are demonstrated in the table 1. Reasons for N discontinuation were: grade 3-4 AE in 6 (13%) pts, Russian nivolumab NPP discontinuation in 27 (56%), patient’s decision in 15 (31%). Median follow up was 48 (4-65) mo. Disease relapse was occurred in 30 (63%) pts. Median PFS in group of patients who achieved CR was 24 mo (95%CI: 11.7-NA) and 4-y PFS was 43.6% (95%CI: 26.9-58.3), in group of PR all patients had disease progression: median PFS was 7.7 mo (95% CI: 5.6-16.5). Only 1 pt died due to progressive multifocal leukoencephalopathy after allo-HSCT. Median OS was not reached, 4-y OS was 92.9% (95%CI: 59.1-99). Retreatment with mono-N was initiated in 22 pts. Median follow up was 33 (7-56) mo. ORR was 73%: CR was achieved in 9 (41%) pts, PR in 7 (32%), indeterminate response in 6 (27%). Median PFS was 24.8 mo (95%CI: 17.2-NA), 3-y PFS 26.7% (95%CI: 7.5-51). Nine (41%) pts demonstrated AE during N retreatment, 4 (18%) pts - grade 3-4 AE.
Conclusion: Patients with r/r cHL who achieved CR after N therapy may demonstrate durable remissions after N discontinuation. In case of disease relapse N retreatment is effective and safe option.