Efficacy of decitabine plus anti-PD-1 camrelizumab in patients with Hodgkin lymphoma who progressed or relapsed after PD-1 blockade monotherapy.

Purpose: Programmed death-1 (PD-1) blockade monotherapy is effective in relapsed/refractory classical Hodgkin lymphoma (cHL), but a subset of patients is recalcitrant to PD-1 inhibitors and only a minority of patients achieves durable remission. Effective treatment regimens for those with relapsed/progressive cHL after single-agent anti-PD-1 are urgently needed. Anti-PD-1 combination with DNA demethylating agent decitabine showed positive preliminary results in our test cohort patients who were resistant to anti-PD-1. Here, we assess the efficacy of decitabine-plus-anti-PD-1 therapy in an expansion cohort and after longer follow-up. Experimental Design: We present the response and progression-free survival rates from patients with relapsed/refractory cHL who relapsed/progressed after prior anti-PD-1 monotherapy, and who received decitabine (10 mg/day, days 1-5) plus the anti-PD-1 camrelizumab (200 mg, day 8), every 3 weeks in a phase 2 trial (ClinicalTrials.gov: NCT02961101 and NCT03250962). Results: Overall, 51 patients (test cohort: 25, expansion cohort: 26) were treated and 50 evaluated for efficacy. The objective response rate was 52% (9 CRs; 36%) in the test cohort, and 68% (6 CRs; 24%) in the expansion cohort. Median progression-free survival with decitabine-plus-camrelizumab was 20.0 and 21.6 months, respectively, which was significantly longer than that achieved with prior anti-PD-1 monotherapy. Durable response was observed in an estimated 78% of patients who achieved CR at 24 months. After decitabine-plus-camrelizumab, the ratio increase of circulating peripheral central memory T-cells directly correlated with both clinical response and progression-free survival. Conclusions: Decitabine-plus-camrelizumab is associated with high response rates and long-term benefits in patients with relapsed/refractory cHL who failed PD-1 inhibitors.