Safety and Efficacy of Anti-PD-1 Monoclonal Antibodies in Patients With Relapsed or Refractory Lymphoma: A Meta-Analysis of Prospective Clinic Trails

Background: Immune checkpoint inhibition therapy with monoclonal antibody against programmed cell death protein 1 (PD-1), including nivolumab and pembrolizumab, has demonstrated powerful clinical efficacy in the treatment of advanced cancers. However, there is no evidence-based systematic review on the safety and efficacy of anti-PD-1 antibody in treating lymphoma. Methods: To evaluate the safety and efficacy of nivolumab/pembrolizumab, we analyzed clinical trials from PUBMED, EMBASE, and The Cochrane Library. For safety analysis, the incidence and exhibition of any grade and grade >= 3 adverse events (AEs) were evaluated. Overall response rate (ORR), 6-month progression-free survival (PFS) and 6-month overall survival (OS) were calculated for efficacy analysis. Results: Overall ten studies and 718 patients (114 non-Hodgkin lymphomas, 604 Hodgkin lymphomas) were enrolled, including 4 phase I studies and 6 phase II studies. The pooled incidences of any grade and grade >= 3 adverse events (AEs) were 74 and 24%, respectively. Drug-related deaths occurred in two patients. The most common any grade AEs were fatigue (14.91%), rash (14.8%), hypothyroidism (13.77%), platelet count decreased (13.54%), pyrexia (13%). The most common grade >= 3 AEs were neutropenia (4.79%), pneumonitis (3.58%), rash (3.38%), and leukopenia (3.31%). Fatigue (p = 0.0072) and rash (p = 0.0078) in any grade AEs were less observed in patients treated with pembrolizumab than nivolumab. The pooled ORR, PFS rate and OS rate were 58, 73, and 96%, respectively. The ORR in patients with Hodgkin lymphomas (HL) was higher than patients with non-Hodgkin lymphomas (NHL) (69.08 vs. 30.77%, p < 0.0001). However, there was no significant difference of efficacy between nivolumab and pembrolizumab. Conclusions: Nivolumab and pembrolizumab have promising outcomes with tolerable AEs and drug-related deaths in patients with relapsed or refractory lymphoma. Pembrolizumab caused less any grade AEs like fatigue and rash than nivolumab. Patients with HL got better response than NHL.