Frailty, Sarcopenia, and Functional Decline After CAR-T Therapy: The Case for Structured Rehabilitation

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment landscape of relapsed or refractory hematologic malignancies, offering unprecedented response rates and durable remissions in diseases such as B-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma, and multiple myeloma. By genetically engineering autologous T cells to recognize tumor-associated antigens, CAR-T therapy enables targeted immune-mediated cytotoxicity against malignant cells. Although early clinical experience has largely focused on acute toxicities including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome improving survival has shifted attention toward the long-term health status of survivors. As the population of CAR-T recipients grows, a broader survivorship framework that incorporates functional outcomes and quality of life has become increasingly important. Emerging evidence suggests that frailty, sarcopenia, and progressive functional decline represent underrecognized complications in patients recovering from CAR-T therapy. These impairments may result from multiple converging factors including systemic inflammation, prior intensive chemotherapy, prolonged hospitalization, corticosteroid exposure, and physical inactivity during treatment. Such changes may have important cardiovascular implications, including reduced cardiorespiratory fitness, impaired exercise tolerance, and increased vulnerability to cardiovascular morbidity. Despite these risks, structured rehabilitation programs remain poorly integrated into CAR-T survivorship care.