A Comprehensive Rehabilitation Framework to help optimize outcomes across the CAR-T Continuum - White Paper Report

Area of Science:

• Oncology
• Hematology
• Rehabilitation Medicine

Background:

• Chimeric antigen receptor T-cell (CAR-T) therapy is a breakthrough for hematologic malignancies.
• CAR-T therapy is linked to severe neuromusculoskeletal toxicities like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
• These toxicities negatively impact patient function, mobility, and quality of life (QoL), with rehabilitation often inconsistently applied.

Purpose of the Study:

• To establish the first comprehensive, consensus-based recommendations for rehabilitation team involvement across the entire CAR-T treatment spectrum.
• Recommendations cover pre-treatment assessment through long-term survivorship.

Main Methods:

• A systematic literature search was performed across major databases (PubMed, Embase, etc.) for publications from 2015-2025.
• International expert consensus was achieved through collaboration with the Eastern Mediterranean Blood and Marrow Transplantation (EMBMT) Group and the Rehabilitation Association for Hematopoietic Cell Transplant.
• Experts included physical therapists, nurse practitioners, and transplant consultants.

Main Results:

• Patients undergoing CAR-T therapy frequently experience neuromusculoskeletal issues, including ICANS (20-60%), CRS-related symptoms (up to 90%), fatigue (up to 90%), myopathy, neuropathy, arthralgia, and avascular necrosis.
• Pre-existing sarcopenia correlates with increased toxicity and reduced survival.
• A tiered rehabilitation model is proposed: baseline assessment, dynamic inpatient care, and 12-18 months of outpatient follow-up, with defined service delivery levels and roles for Advanced Clinical Practitioners (ACPs).

Conclusions:

• Neuromusculoskeletal rehabilitation is a critical, underutilized aspect of CAR-T therapy.
• Systematic integration of rehabilitation, supported by specialized roles, can decrease morbidity, enhance functional outcomes and QoL, and improve healthcare efficiency.
• Further prospective trials are needed to validate these recommendations.