A Comprehensive Rehabilitation Framework to Help Optimize Outcomes Across the CAR-T Continuum-White Paper Report

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematologic malignancies but is associated with significant neuromusculoskeletal toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), fatigue, myopathy, arthralgia, and avascular necrosis. These complications profoundly impact functional status, mobility, and quality of life (QoL), yet structured rehabilitation remains inconsistently integrated into CAR-T care pathways.

To develop the first comprehensive, consensus-based recommendations outlining the role of rehabilitation team across the CAR-T treatment continuum, from pre-treatment assessment through long-term survivorship.

A systematic literature search of PubMed, Embase, Science Direct, Taylor & Francis, and CINAHL Ultimate was conducted for publications from 2015 to 2025. International expert consensus was obtained through collaboration with the Eastern Mediterranean Blood and Marrow Transplantation (EMBMT) Group and the Rehabilitation Association for Hematopoietic Cell Transplant, specialist from a diverse clinical background including physical therapy, nurse practitioner and transplant consultants.

Post CAR-T treatment patients can suffer from various neuromusculoskeletal manifestations including ICANS (20% to 60%), CRS-related musculoskeletal symptoms (up to 90%), persistent fatigue (up to 90%), cytokine-induced myopathy, peripheral neuropathies, arthralgias, and avascular necrosis. Pre-existing sarcopenia is associated with higher toxicity rates and reduced survival. A tiered rehabilitation model is proposed comprising: (1) comprehensive pre-CAR-T baseline assessment including functional, neurological, and QoL measures; (2) dynamic inpatient rehabilitation adapting to daily fluctuations in CRS/ICANS severity and cytopenias; and (3) structured outpatient follow-up for at least 12-18 months. Three service delivery levels (minimum essential, intermediate, and advanced/model care) are outlined, with recommendations for embedding rehabilitation services within multidisciplinary CAR-T teams and developing Advanced Clinical Practitioner (ACP) roles.

Neuromusculoskeletal rehabilitation is an essential, yet underutilized, component of CAR-T therapy care. Systematic integration of rehabilitation across the treatment continuum, supported by specialized practitioner roles, has the potential to reduce morbidity, improve functional outcomes and QoL, and optimize healthcare resource utilization. Prospective trials validating these recommendations remain a priority.