Efficacy and safety of PD-1/PD-L1 immune checkpoint inhibitors in treating non-Hodgkin lymphoma: A systematic review and meta-analysis of clinical trials

Abstract

Background: Immunotherapy with programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors has been widely used in the treatment of solid tumors and Hodgkin lymphoma, demonstrating powerful efficacy and good safety. However, there is no systematic review and meta-analysis to fully investigate the efficacy and safety of PD-1/PD-L1 inhibitors in treating non-Hodgkin lymphoma (NHL). Methods: We searched PubMed, EMBASE, The Cochrane Library, China National Knowledge Infrastructure, Wanfang database, and abstracts of conference proceedings of annual meetings up to January 23, 2022, to identify eligible clinical trials. To evaluate the efficacy of PD-1/PD-L1 inhibitors, objective response rate (ORR), complete response rate (CRR), 1-year overall survival rate, and 1-year progression-free survival rate were analyzed. For safety analysis, we calculated rates of any grade and grade ≥3 treatment-related adverse events. Results: Overall 22 studies and 1150 participants were enrolled in this meta-analysis. The pooled ORR, CRR, 1-year overall survival, and 1-year progression-free survival rates were 0.43 (95% confidence interval [CI], 0.33–0.54), 0.21 (95% CI, 0.13–0.31), 0.72 (95% CI, 0.58–0.89), and 0.42 (95% CI, 0.29–0.62), respectively. The ORR and CRR in the combination immunochemotherapy subgroup (0.65 and 0.41) were higher than those in the monotherapy (0.27 and 0.09) and combination chemotherapy (0.39 and 0.19) subgroups. This study was registered with PROSPERO (#CRD 42022316805). Conclusion: Given that there were limited clinical trials and relatively few relevant studies, we conducted this meta-analysis to fully elucidate the efficacy and safety of PD-1/PD-L1 inhibitors in NHL. Our results suggested that PD-1/PD-L1 inhibitors improved outcomes of responses as well as survival rates in NHL patients with tolerable adverse events. More well-designed randomized clinical trials are still needed to further confirm our findings.

The prognostic significance of programmed cell death protein 1 and its ligand on lymphoma cells and tumor-immune cells in diffuse large B-cell lymphoma, not otherwise specified

“…Identifying additional biomarkers and carefully assessing them to precisely define the effectiveness of immunotherapy are therefore critical for improved treatment outcomes, which are being investigated in several ongoing studies. 3 , 4 , 5 …”

The 3’ non-coding sequence negatively regulates PD-L1 expression and its regulators are systematically identified in pan-cancer

“…FDAapproved immunohistochemistry test for PD-L1 expression is a prerequisite for treatment with anti-PD-1/PD-L1 therapy [6]. Most tumors, however, are not effective with single-agent PD-1 antibodies, and only classic Hodgkin's lymphoma is effective with PD-1 inhibitors alone [7]. Also, in about 5-10% of patients, severe immune-related in ammatory reactions develop, and 15-35% of patients experienced disease recurrence after a period of PD-1/PD-L1 monoclonal antibody use [7].…”

The 3′ Non-Coding Sequence Negatively Regulates PD-L1 Expression, and Its Regulators Are Systematically Identified in Pan-Cancer

“…A FDA-approved immunohistochemistry test for PD-L1 expression is a prerequisite for treatment with anti-PD-1/PD-L1 therapy [ 6 ]. However, most tumors do not respond effectively to single-agent PD-1 antibodies, with only classic Hodgkin’s lymphoma showing effectiveness with PD-1 inhibitors alone [ 7 ]. Furthermore, approximately 5–10% of patients develop severe immune-related inflammatory reactions, and 15–35% of patients experience disease recurrence after a period of PD-1/PD-L1 monoclonal antibody use [ 7 ].…”