Efficacy and Safety of Immune Checkpoint Inhibitors in the Treatment of Hematologic Malignancies: An Umbrella Review of Systematic Reviews and Meta‐Analyses

BACKGROUND: This umbrella review summarizes evidence from systematic reviews and meta-analyses on the efficacy and safety of immune checkpoint inhibitors (ICIs) in hematologic malignancies. To our knowledge, this is the first umbrella review to comprehensively evaluate ICIs across multiple hematologic cancers. The goal is to clarify their therapeutic potential, highlight major safety issues, and provide evidence-based guidance for future clinical and research applications. METHODS: A comprehensive search was conducted across PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews up to May 2025. Systematic reviews and meta-analyses investigating ICIs in hematologic malignancies were included. The AMSTAR tool was used to assess methodological quality, and the GRADE system was employed to evaluate the quality of evidence for each outcome. RESULTS: A total of 24 meta-analyses met the inclusion criteria, covering 39 unique interventions. ICIs demonstrated significant efficacy in multiple myeloma (MM), relapsed/refractory natural killer T-cell lymphoma (R/R NKT), relapsed/refractory chronic lymphocytic leukemia (R/R CLL), and relapsed/refractory primary mediastinal B-cell lymphoma (R/R PMBCL). Pembrolizumab combined with lenalidomide and dexamethasone (PLD) significantly improved overall survival (OS) in MM (HR: 0.51, 95% CI: 0.32 to 0.82, high quality). In R/R NKT, sintilimab and other ICIs showed moderate overall response rates (ORR) with favorable safety profiles. Pembrolizumab also demonstrated moderate efficacy in R/R CLL and R/R PMBCL, with low rates of severe adverse events. However, the studies exhibited significant heterogeneity, and publication bias was detected in certain outcomes, highlighting the need for cautious interpretation. CONCLUSIONS: ICIs show promising therapeutic potential in several hematologic malignancies, particularly R/R NKT, MM, R/R CLL, and R/R PMBCL. While safety profiles are generally favorable, certain regimens are associated with manageable toxicities. Future research should focus on optimizing combination therapies, refining patient selection criteria, and addressing study heterogeneity to enhance the clinical application of ICIs in hematologic cancers.