Exercise Prehabilitation for Older Adults Undergoing CAR-T: Feasibility and Preliminary Outcomes from a Single-Arm Pilot Study

Introduction

Older adults with hematological malignancies frequently present with physiological deconditioning and frailty that portend worse CAR-T outcomes. Exercise prehabilitation (“prehab”) may improve CAR-T outcomes by enhancing physiological reserve prior to treatment, but feasibility has not been established. We evaluated the feasibility and acceptability of exercise prehab and explored preliminary outcomes among older adults undergoing CAR-T.

Methods

We enrolled older adults (age ≥ 65) preparing for CAR-T in a single-arm pilot study involving ≥ 4 weeks of home-based, multimodal exercise prehab. Assessments occurred at baseline (T0; peri-apheresis) and follow-up (T1; peri-lymphodepletion chemotherapy). Prehab targets included independent aerobic exercise (≥ 90 min/week) and supervised resistance training (RT; 2x/week), aligning with exercise guidelines for individuals undergoing cancer treatment. Certified exercise trainers supervised and guided all RT sessions 1:1 via Zoom videoconference. RT sessions included 6 modifiable exercises targeting major muscle groups (squat/chair stand, chest press, deadlift, row, abdominal stabilization, and shoulder raise), each performed for 2 sets of 12-15 repetitions using graded resistance tube sets and loaded progressively based on perceived exertion. Feasibility evaluation included enrollment (% of approached patients who participated), retention (% of participants who completed T1 assessments), and adherence (performance of aerobic exercise and RT sessions). Acceptability was evaluated using Likert-type items with possible responses ranging 1 (“strongly disagree”) to 5 (“strongly agree”). Participants self-reported aerobic exercise using a modified Godin Physical Activity Questionnaire. Exploratory outcomes included changes in functional fitness (6-minute walk distance, 30-second arm curl repetitions, and 30-second chair stand repetitions) and health-related quality of life (HRQOL) measured by SF-12 Health Survey physical and mental component scores (PCS and MCS). Skeletal muscle index (SMI) was measured using abdominal images from restaging CT scans, with changes from pre- to post-CAR-T compared to a group of retrospectively-identified, non-prehab patients frequency matched on age, sex, and timeframe of post-CAR-T imaging (30 vs. 90 days). We used t-tests or non-parametric alternatives to evaluate changes in exploratory outcomes.

Results

We report initial results obtained from 18 of our target 20 pilot participants, whom we recruited from 27 approached patients (current enrollment rate = 18/27 or 67%). Participants were 33% female, 83% non-Hispanic White, 11% non-Hispanic Black, 6% Hispanic or Latino, and had median age 77 (range 65-86). Diagnoses include lymphoma (67%), multiple myeloma (28%), and leukemia (6%). One participant dropped out due to disease progression, 1 was excluded due to decision not to proceed with CAR-T, and 2 are currently engaging in prehab at the time of reporting (current retention = 14/16 or 88%). To date, 14 patients who completed prehab reported a median of 90 weekly minutes of independent aerobic exercise (range 40-750) and attended 81.1% ± 21.1% (mean ± SD) of target RT sessions. Acceptability ratings were high (mean ± SD score across all items = 4.8 ± 0.1) and ranged from 4.6 (“I was able to do the exercises without difficulty”) to 4.9 (“The exercises were worth my time”). Patients who completed prehab demonstrated statistically significant improvements in 6-minute walk distance (mean increase 13.8% ± 16.0%, p = 0.03) and 30-second arm curl repetitions (mean increase 15.9% ± 17.8%, p = 0.01). Improvements in 30-second chair stand repetitions (mean increase 11.4% ± 18.9%, p = 0.07), PCS (mean increase 1.9 ± 7.1, p = 0.5), and MCS (mean increase 4.5 ± 2.3, p = 0.08) were not statistically significant. Participants with available pre- and post-CAR-T CT imaging (n = 9) demonstrated maintenance of SMI compared to 22 non-prehab comparison patients (mean change 0.4 ± 4.0 cm²/m² vs. -3.5 ± 3.4 cm²/m², p = 0.01 for difference in change).

Conclusions

These data demonstrate the feasibility and acceptability of home-based exercise prehab for older patients undergoing CAR-T, with potential benefits including improvements in functional fitness, HRQOL, and muscle maintenance. The role of prehab in improving clinical care for older adults undergoing CAR-T warrants further study.

Castaneda:Legend Biotech: Consultancy; Janssen: Consultancy; BMS: Consultancy. Chavez:Allogene: Consultancy; Janssen: Honoraria; Lilly: Honoraria, Speakers Bureau; Cellectis: Consultancy; Merck: Research Funding; AstraZeneca: Consultancy; Novartis: Consultancy; Abbvie: Consultancy; BeiGene: Consultancy, Honoraria, Speakers Bureau; ADC Therapeutics: Consultancy; GenMab: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy. Faramand:Orca Bio: Research Funding; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Autolus: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria. Jain:Kite/Gilead: Consultancy, Research Funding; Myeloid Therapeutics: Consultancy; Incyte: Research Funding; Loxo: Research Funding. Jim:SBR Biosciences: Consultancy; Kite Pharma: Research Funding. Lazaryan:Sanofi: Consultancy, Honoraria, Other: Scientific advisory board. Mirza:BMS: Speakers Bureau. Shah:Pepromene Bio: Other: DSMB; Autolus, Beigene, Century Therapeutics, Deciphera, Jazz, Kite/Gilead, Pfizer, Precision Biosciences, Novartis, Takeda: Consultancy; Jazz Pharmaceuticals, Kite-Gilead, Servier: Research Funding; Eli Lilly: Consultancy; Bristol Myers Squibb: Consultancy; AstraZeneca: Consultancy; Amgen: Consultancy; Jazz Pharmaceuticals: Consultancy; Kite Pharma: Consultancy; Adaptive Biotechnologies: Consultancy. Locke:Kite, a Gilead Company: Consultancy, Other: Travel support, Research Funding; Pfizer: Consultancy; CERo Therapeutics: Research Funding; 2SeventyBio: Research Funding; Calibr: Consultancy; Cowen: Consultancy; Celgene: Consultancy; BMS: Consultancy, Research Funding; Amgen: Consultancy; Sana: Consultancy; Umoja: Consultancy; Wugen: Consultancy; Moffit Cancer Center: Patents & Royalties: cellular immunotherapy; ASH: Honoraria, Other: Travel support; Aptitude Health: Honoraria; Leukemia and Lymphoma Society Scholar in Clinical Research: Research Funding; National Cancer Institute: Research Funding; Gerson Lehrman Group (GLG): Consultancy; Gilead Company: Consultancy; Aptitude Health: Honoraria; Communications CARE Education: Honoraria; Caribou: Consultancy; A2: Consultancy; Society for Immunotherapy of Cancer: Honoraria; iMedX: Honoraria; Clinical Care Options Oncology: Honoraria; BioPharma: Honoraria; Novartis: Consultancy, Research Funding; Legend Biotech: Consultancy; Janssen: Consultancy; Iovance: Consultancy; Allogene: Consultancy, Research Funding; GammaDelta Therapeutics: Consultancy; Bluebird Bio: Consultancy, Research Funding; Emerging Therapy Solutions Gerson Lehman Group: Consultancy; ecoR1: Consultancy; Cellular Biomedicine Group: Consultancy. Freeman:BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy; Seattle Genetics: Consultancy; Incyte: Consultancy; Celgene: Consultancy; Abbvie: Consultancy; Sanofi: Consultancy; ONK therapeutics: Consultancy; Janssen: Consultancy, Research Funding; Roche/Genentech: Research Funding.