Language
English
Publication Date
3-1-2024
Journal
Cytotherapy
DOI
10.1016/j.jcyt.2023.11.013
PMID
38149948
PMCID
PMC10922117
PubMedCentral® Posted Date
3-1-2025
PubMedCentral® Full Text Version
Author MSS
Abstract
Chimeric antigen receptor (CAR) T-cells are an emerging therapy for refractory lymphomas. Clonal hematopoiesis (CH), the preferential outgrowth of mutated bone marrow progenitors, is enriched in lymphoma patients receiving CAR-T cells. CAR-T therapy requires conditioning chemotherapy and often induces systemic inflammatory reactions, both of which have been shown to promote expansion of CH clones. Thus, we hypothesized that pre-existing CH clones could expand during CAR-T cell treatment. We measured CH at 154 timepoints longitudinally sampled from 26 patients receiving CD30.CAR-T therapy for CD30+ lymphomas on an investigational protocol (NCT02917083). Pre-treatment CH was present in 54% of individuals and did not correlate with survival outcomes or inflammatory toxicities. Longitudinal tracking of single clones in individual patients revealed distinct clone growth dynamics. Initially small clones, defined as VAF < 1%, expanded following CAR-T administration, compared with relatively muted expansions of larger clones (3.37-fold vs. 1.20-fold, P = 0.0014). Matched clones were present at low magnitude in the infused CD30.CAR-T product for all CH cases but did not affect the product's immunophenotype or transduction efficiency. As cellular immunotherapies expand to become frontline treatments for hematological malignancies, our data indicates CAR-T recipients could be enriched for CH, and further longitudinal studies centered on CH complications in this population are warranted.
Keywords
Humans, Receptors, Chimeric Antigen, Clonal Hematopoiesis, Immunotherapy, Adoptive, Lymphoma, Immunotherapy, Hematopoiesis
Published Open-Access
yes
Recommended Citation
Kapadia, Chiraag D; Rosas, Gerardo; Thakkar, Sachin G; et al., "Incipient Clonal Hematopoiesis Is Accelerated Following CD30.CAR-T Therapy" (2024). Huffington Center on Aging Staff Publications. 44.
https://digitalcommons.library.tmc.edu/aging_research/44