Safety and Efficacy in Relapsed or Refractory Classic Hodgkin's Lymphoma Treated with PD-1 Inhibitors: A Meta-Analysis of 9 Prospective Clinical Trials

BACKGROUND: Classic Hodgkin's lymphoma (cHL) is characterized by the unique biology in which rare Hodgkin-Reed-Sternberg cells propagate an immunosuppressive microenvironment. Checkpoint inhibitors that target the interaction of PD-1 immune checkpoint receptors have demonstrated remarkable activities in various cancers, such as cHL. This study aims to evaluate the safety and efficacy of PD-1 inhibitors in treating relapsed or refractory cHL (rrHL). METHODS: We searched PubMed, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang, Chinese Biological Medical Literature, and Abstracts of Conference proceedings of annual meetings without any language restrictions to limit language bias (up to January 2019) for prospective clinical trials that evaluate PD-1 inhibitors in treating relapsed or refractory cHL. RESULTS: A total of 9 prospective clinical trials with 731 patients were included in the meta-analysis. The pooled risks of all-grade and grade ≥3 adverse events (AEs) were 0.86 (95% CI: 0.66–0.98) and 0.21 (95% CI: 0.17–0.24), respectively. The pooled response, complete response, partial response, and stable disease rates were 0.74 (95% CI: 0.70–0.79), 0.24 (95% CI: 0.18–0.34), 0.48 (95% CI: 0.41–0.55), and 0.15 (95% CI: 0.12–0.17), respectively. The pooled 6-month progression-free survival and 1-year overall survival rates were 0.76 (95% CI: 0.72–0.79) and 0.93 (95% CI: 0.90–0.96), correspondingly. CONCLUSIONS: Our meta-analysis suggested that anti-PD1 monoclonal antibodies improve the outcomes of response and survival rates with tolerable AEs in cHL. However, evidence of immune checkpoint inhibitors for patients with cHL remained insufficient. Well-designed randomized controlled trials or at least nonrandomized trials with a control group should be conducted to confirm the findings of this meta-analysis.