Clonal Hematopoiesis and CAR T Cell Therapy: From Biological Crosstalk to Clinical Implications

Abstract

Clonal hematopoiesis (CH) is increasingly recognized as a significant biological phenomenon in aging and cancer, marked by the expansion of hematopoietic stem and progenitor cells harboring somatic mutations in genes associated with myeloid neoplasms. While CH is strongly linked to a spectrum of inflammatory diseases and hematologic malignancies, its role in shaping responses to cancer immunotherapy—especially chimeric antigen receptor (CAR) T cell therapy—has only recently begun to emerge. This review explores the interplay between CH and CAR T cell therapy, highlighting CH prevalence in treated populations, post-therapy clonal dynamics, inflammatory toxicities, and risk of therapy-related myeloid neoplasms. We also discuss the differential effects of specific CH mutations on hematopoiesis, immune cell function, and CAR T cell persistence. Understanding the functional implications of CH in the context of CAR T cell therapy holds the potential to refine patient selection, tailor toxicity management, and develop personalized immunotherapeutic approaches.