Abstract P113

Eight-year outcomes after nivolumab discontinuation in patients with relapsed/refractory classic Hodgkin lymphoma

Background: The optimal duration of immune checkpoint inhibitor (ICI) therapy in relapsed/refractory classic Hodgkin lymphoma (r/r cHL) and its curative potential remain uncertain. Limited data suggest that discontinuation of therapy after achievement of complete response (CR) may lead to durable remissions, while ICI retreatment can be effective. We analyzed long-term outcomes in an expanded cohort of patients who discontinued nivolumab (nivo) in CR and evaluated the efficacy and safety of nivo retreatment.

Methods: This retrospective study included 47 patients with r/r cHL treated with nivo at a dose of 3 mg/kg (60%) or 40 mg (40%) (Table 1). All patients discontinued therapy in CR. At relapse, nivo monotherapy was reinitiated in 19 pts. After discontinuation, patients were monitored every 6 months for 2 years, then clinically with imaging as indicated. Responses were assessed by PET/CT using LYRIC criteria; adverse events (AEs) by CTCAE 5.0. PFS and OS were evaluated after discontinuation, and ORR, PFS, OS, and AEs were evaluated after retreatment. Univariate Cox regression assessed clinical factors associated with PFS (primary r/r, sex, prior auto-HCT, prior brentuximab vedotin, number of prior therapy lines, presence of B symptoms, ECOG PS at nivo initiation, nivo dose, occurrence of severe AEs, completion of 24 cycles of nivo, and early CR at 3 mo).

Results: Median follow-up was 95 (13-111) mo. Nivo was discontinued due to AEs (n=5, 11%), cessation of the national nivo compassionate use program (n=19, 40%), or patient/physician decision (n=23, 49%). Relapse occurred in 24 (51%) pts. Median PFS was 25.8 mo (95%CI: 14.5-NA); 8-y PFS was 46.8% (95% CI: 34.2-64.2). Median OS was not reached; 8-y OS was 89.8% (95% CI: 80.8-99.8). No clinical factors were significantly associated with PFS. ORR after nivo retreatment (n=19) was 74% (CR 47%). Median follow-up was 68 (25-96) mo. Median PFS was 22.7 mo (95% CI: 16.5-NA); 5-y PFS was 34.7% (95% CI: 18.4-65.5). Median OS was not reached; 5-y OS was 76.5% (95% CI: 58.7-99.5). AEs during retreatment occurred in 42% of patients, with grade 3–4 in 16%.

Conclusion: Long-term follow-up of patients with r/r cHL who discontinued nivo in CR demonstrates that a substantial proportion of patients remain relapse-free, raising the possibility of cure in this population. These findings should be considered when developing treatment strategies, including decisions regarding the role of consolidative allogeneic HCT.