Efficacy of decitabine plus anti-PD-1 camrelizumab in patients with Hodgkin lymphoma who progressed or relapsed after PD-1 blockade monotherapy
Mené sur 51 patients atteints d'un lymphome hodgkinien refractaire ou récidivant, cet essai évalue l'efficacité, du point de vue du taux de réponse objective et de la survie sans progression, d'un traitement combinant décitabine et camrélizumab, après l'échec d'inhibiteurs anti-PD-1 en monothérapie
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.