Clinical Outcomes of Next-Generation Chimeric Antigen Receptor T-Cell Therapy in Acute Lymphoblastic Leukemia
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Abstract
Objective: To evaluate efficacy, durability, and safety of next-generation chimeric antigen receptor T-cell therapies in relapsed or refractory acute lymphoblastic leukemia. Design: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines with a predefined protocol. Subjects/Patients: Pediatric and adult patients with relapsed or refractory acute lymphoblastic leukemia treated with next-generation chimeric antigen receptor T-cell therapies using dual or multi-antigen targeting, cytokine-armored constructs, or logic-gated systems. Ten open-access studies including 327 heavily pretreated patients were analyzed. Methods: Electronic databases were systematically searched for eligible studies. Extracted data included patient characteristics, chimeric antigen receptor design, remission rates, durability, relapse patterns, and toxicity. Risk of bias was assessed. Results: Complete remission rates ranged from seventy-eight percent to ninety-two percent, exceeding historical outcomes. Dual or multi-antigen targeting reduced antigen-negative relapse to less than ten percent. Cytokine-armored constructs showed enhanced persistence and prolonged remission, with engineered T cells detectable beyond six months in over half of patients. Logic-gated systems showed comparable efficacy with improved specificity. Cytokine release syndrome and neurotoxicity were manageable. Conclusion: Next-generation chimeric antigen receptor T-cell therapies demonstrate robust efficacy, improved durability, and acceptable safety, representing a meaningful evolution of adoptive cellular immunotherapy requiring validation in larger standardized trials.
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Copyright (c) 2026 Dr. Birupaksha Biswas, MD, Dr. Suhena Sarkar, MD
This work is licensed under a Creative Commons Attribution 4.0 International License.
Creative Commons License All articles published in Annals of Medicine and Medical Sciences are licensed under a Creative Commons Attribution 4.0 International License.
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