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. Trial Registration Clinical trials.gov number: NCT03996239.