Safety and efficacy of programmed cell death-1 inhibitors in relapsed immune-privileged site lymphoma: A systematic review and meta-analysis

Background: Large B-cell lymphoma of immune-privileged sites (LBCL-IP) is a rare subtype characterized by immune evasion properties. Primary central nervous system lymphoma (PCNSL) and primary testicular lymphoma (PTL) are examples of LBCL-IP associated with programmed cell death protein 1 (PD-1). Few studies have investigated the use of PD-1 inhibitors in patients with relapsed PCNSL and PTL. Objective: To conduct a systematic review evaluating the efficacy and safety of PD-1 inhibitors in patients with relapsed PCNSL and PTL. Methods: We searched the PubMed, Embase, and Scopus databases for relevant studies. The inclusion criteria focused on adult patients diagnosed with relapsed PCNSL or PTL who were treated with PD-1 inhibitors. We excluded case reports or series with fewer than five participants, review articles, and animal studies. A random-effects model with the DerSimonian‒Laird method analyzed the pooled complete response rate (CRR), partial response rate (PRR), overall response rate (ORR), and progression-free survival (PFS) rate. Results: Seven studies comprising 127 patients (124 with relapsed PCNSL and 3 with PTL) were included. All patients were treated with either nivolumab or pembrolizumab. The pooled CRR was 42.8% (95% CI, 25.7%‒60.0%; I2 = 75.25%; p