Optimizing bridging radiotherapy prior to CAR-T cell therapy: An evidence-based approach

Bridging radiotherapy has emerged as a valuable strategy to ensure optimal conditions for chimeric antigen receptor T-cell (CAR-T) therapy in relapsed or refractory hematologic malignancies. By controlling disease burden and maintaining clinical stability in the interval between leukapheresis and CAR-T infusion, it helps counteract the risk of tumor progression that can diminish treatment efficacy. Evidence from diffuse large B-cell lymphoma (DLBCL) and other lymphomas supports the use of hypofractionated radiotherapy to achieve rapid local control with minimal delays, while preliminary data in multiple myeloma expand its applicability. Radiotherapy's immunomodulatory effects, including enhanced antigen presentation and inflammation, may bolster CAR-T cell activity, though careful consideration is required to avoid potential immunosuppressive consequences. The optimal integration of bridging radiotherapy encompasses timing after leukapheresis, rapid planning and delivery, judicious choice of fractionation, and close coordination between hematology and radiotherapy teams. Tailoring dose and technique further refines the therapeutic window, minimizing toxicity while maintaining efficacy. These evidence-based practice propositions provide a comprehensive framework for implementing bridging radiotherapy. By outlining indications, workflow, fractionation schemes, and technical approaches, these guidelines facilitate the seamless incorporation of radiotherapy into CAR-T therapy protocols, ultimately aiming to improve patient outcomes through enhanced disease control and synergistic antitumor immunity.