Safety and efficacy of PD-1 and PD-L1 inhibitors in relapsed and refractory Hodgkin's lymphoma: a systematic review and meta-analysis of 20 prospective studies

Background: Inhibitors of programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) have been used in the treatment of relapsed and refractory Hodgkin's lymphoma (R/R HL) recently. To further understand the safety and efficacy of PD-1/PD-L1 inhibitors in R/R HL, we conducted this meta-analysis.Methods: Databases and the Clinical Registration Platforms have been systematically searched for related studies by March 2022. For safety analysis, the incidence and exhibition of any grade and grade 3 or higher adverse effects (AEs) were evaluated. Besides, severe AEs (SAEs), treatment-related deaths, and AEs leading to treatment discontinuation were summarized. The overall response rate (ORR), complete response (CR) rate, partial response (PR) rate, progression-free survival (PFS), overall survival (OS), and duration of response (DOR) were calculated for efficacy analysis. All processes were implemented mainly through the package Meta and MetaSurv of software R 4.1.2.Results: Overall 20 studies and 1440 patients were enrolled. The pooled incidence of any grade and grade 3 or higher AEs were 92% and 26%, respectively. The pooled ORR, CR rate and PR rate were 79%, 44% and 34%, respectively. The most common AEs were neuropathy (29%), nausea (27%), pyrexia (26%), and leukopenia (25%), and the most common grade 3 or higher AEs included leukopenia (10%), infusion reaction (8%), weight gain (3%), and neutropenia (2.7%). In survival analysis, pembrolizumab monotherapy appeared to perform better compared to nivolumab monotherapy.Conclusions: PD-1/PD-L1 inhibitors show promising efficacy and tolerable AEs in the treatment of R/R HL.