Next-Gen immunotherapy inhematological malignancies: A systematic review and meta-analysis oftranslational breakthroughs, regulatory milestones, and clinical trial trajectories (2018–2025)

Background: Despite transformative advances in the management of hematological malignancies, relapse and therapeutic resistance remain major clinical challenges. Immunotherapeutic agents, including immune checkpoint inhibitors, bispecific T-cell engagers, antibody–drug conjugates, and chimeric antigen receptor (CAR)-engineered therapies, have redefined treatment paradigms.Objective: This meta-analysis critically evaluated the efficacy, safety, and regulatory trajectory of immunotherapies for hematological malignancies between 2018 and 2025, integrating trial-level outcomes and mechanistic insights to delineate the therapeutic landscapes and clinical decision frameworks. Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and a preregistered International Prospective Register of Systematic Reviews protocol (CRD420251118864). PubMed, Embase, Cochrane Library, Scopus, and ClinicalTrials.gov were searched for eligible randomized and nonrandomized trials investigating immunotherapies for leukemia, lymphoma, and plasma cell dyscrasia. Pooled hazard ratios (HRs), risk ratios (RRs), and subgroup analyses were performed using a random-effects model. The risk of bias was assessed using RoB2, and the certainty of evidence was graded using the GRADE methodology. Results: Of the 8120 screened records, 142 studies were included (n > 48,000 patients). CAR-T cell therapies achieved superior complete response rates (62.3%, 95% confidence interval: 58.1– 66.5) in B-cell malignancies. Immune checkpoint inhibitors conferred limited benefits beyond Hodgkin’s lymphoma (hazard ratio for overall survival: 0.88; 95% confidence interval: 0.75–1.02). Bispecific T-cell engagers and antibody–drug conjugates demonstrated efficacy in the treatment of refractory diseases with manageable toxicity. Regulatory approval (Food and Drug Administration/European Medicines Agency) peaked between 2022 and 2024. Conclusions: Immunotherapy for hematological malignancies has entered the maturation phase, with CAR-T cells and modular constructs delivering durable responses. Integration of genomics and microenvironmental modulators is the next frontier in curative immunotherapy.