Background
Chimeric antigen receptor T-cell (CAR-T) therapy is associated with substantial physiological stress and treatment-related toxicities, placing patients who are frail, sarcopenic, or have reduced cardiorespiratory fitness (VO₂peak) at increased risk of adverse outcomes. These patients experience higher rates of immune effector cell-associated neurotoxicity syndrome and poorer progression-free and overall survival following CAR-T therapy. Strategies to improve physiological reserve before CAR-T therapy may enhance treatment tolerance and clinical outcomes.
Aim
To determine the feasibility and efficacy of a 4-week exercise prehabilitation intervention for adults preparing to undergo CAR-T therapy. Findings will inform the design of a future randomised controlled trial.
Methods
A prospective, single-arm pilot feasibility study. Adults (≥18 years) with lymphoma scheduled to receive CAR-T therapy at The Alfred Hospital, Melbourne, will be invited to participate.
Baseline and post-prehabilitation assessments will be conducted in person at the Baker Heart and Diabetes Institute and include cardiopulmonary exercise testing, Fried Frailty Phenotype, the five-times sit-to-stand test, dual-energy X-ray absorptiometry, echocardiography, electrocardiography, and the Exercise Self-Efficacy Scale.
Participants will receive an individually tailored aerobic and progressive resistance exercise program based on baseline testing and symptom status. Exercise will be prescribed by an accredited exercise physiologist and supervised twice weekly via telehealth (45-minute sessions) for up to four weeks.
The primary outcome is feasibility, assessed using predefined criteria for recruitment, intervention completion, attendance, adherence, exercise tolerance, and safety. Secondary outcomes include program acceptability, cardiorespiratory fitness (VO₂peak), body composition, cardiac structure and function, frailty, muscle strength, and exercise self-efficacy.
Current Status
The study has received grant funding from Gilead Sciences and ethics approval from the Alfred Hospital Human Research Ethics Committee. Recruitment is underway, with ten participants enrolled toward the target sample of twenty.