Impact of Exercise on Clonal Hematopoiesis.

BACKGROUND: Clonal hematopoiesis (CH) is more prevalent in cancer patients and is associated with excess all-cause mortality (ACM) risk compared to patients without CH. Interventions to mitigate risk are not available. OBJECTIVES: The objective of the study was to investigate whether exercise reduces CH prevalence and excess ACM risk of CH in cancer patients. METHODS: We integrated genomic sequencing data with detailed exercise and clinical annotation from 2 retrospective studies: 3,539 patients with solid tumors from the MSK-IMPACT (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) and 1,142 patients with primary breast cancer from CANTO (CANcer TOxicities). Patients were classified as nonexercisers (ie, 0 metabolic equivalent of task-h/week) or exercisers (ie, >0 metabolic equivalent of task-h/week). We then conducted a remotely-supervised structured exercise therapy study in 4 patients with cancer and CH. RESULTS: In multivariable analysis, CH prevalence was not different between exercisers and nonexercisers in MSK-IMPACT (OR: 0.95; 95% CI: 0.8 to 1.13; adjusted Firth's logistic regression) or CANTO (OR: 1.28; 95% CI: 0.89-1.84; adjusted Firth's logistic regression). Patients with CH had a higher unadjusted hazard of ACM relative to patients without CH (HR: 1.41; 95% CI: 1.23-1.62). Relative to non-CH nonexercisers, CH-exercisers had a lower adjusted hazard of ACM (HR: 0.69; 95% CI: 0.55-0.87). In the prospective exercise study, cardiovascular risk factors were improved; no changes in peripheral blood somatic variant allele frequency were observed. CONCLUSIONS: Exercise was not associated with CH burden but does reduce excess ACM of CH in patients with cancer. Further research is needed to investigate the exercise-CH relationship in cancer and other populations. (Researching the Effect of Aerobic Exercise on Cancer; NCT039962390).