Effectiveness of chemotherapy after anti-PD-1 blockade failure for relapsed and refractory Hodgkin lymphoma

Programmed death-1 (PD1) blockade is an efficient and safe therapeutic option in patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). However, a substantial proportion of patients' progresses or loses the response to anti-PD1 treatment. We retrospectively investigated the effectiveness of salvage chemotherapies (CHT) for unsatisfactory response to anti-PD1, in 25 R/R cHL patients. Twenty-three patients (92%) were refractory to the last treatment before anti-PD1. After a median of 14 cycles (range 3-52), 68% (17/25) of patients had unsatisfactory responses to anti-PD1 therapy, whereas 6 had a partial response (PR) and 2 patients achieved complete response (CR), with an overall response rate (ORR) of 32%. After a median time of 1.5 months, 15 patients received a single agent treatment and 10 had a multi-agents regimen, due to the failure of PD1 blockade. The ORR was 60% (8 CR and 7 PR). Seven patients (3 in PR and 4 in CR) underwent a consolidation strategy with stem cell transplantation. Median progression-free survival (PFS) with salvage treatment was reached at 19.1 months, while median PFS after anti-PD1 has been reached at 8.2 months. After a median follow-up of 32.4 months, 6 patients died while 13 are still in CR. The median overall estimated from the start of CHT was not reached. The efficacy of treatment following anti-PD1 is not yet established, especially in lymphoma patients. To note, in our series, a subset of heavily pre-treated and chemo-refractory patients increased response rates to and survival with CHT given after exposure to immune-checkpoint inhibitors.