Impact of clonal hematopoiesis of indeterminate potential on treatment outcomes in multiple myeloma patients undergoing CAR-T cell therapy
5 affiliations
- 1Department of Medicine, Division of Hematology/Oncology, UCLA, Los Angeles, CA USA
- 2Department of Medical Oncology, Massachusetts General Hospital, Boston, MA USA
- 3Department of Medicine Statistics Core, UCLA, Los Angeles, CA USA
- 4Department of Pathology and Laboratory Medicine, UCLA, Los Angeles, CA USA
- 5Department of Pathology & Laboratory Medicine, School of Medicine, University of California, Irvine, CA USA
Abstract
Clonal hematopoiesis of indeterminate potential (CHIP) is the presence of hematologic malignancy-associated somatic mutations in patients without hematologic malignancies. In multiple myeloma (MM), the implications of CHIP on chimeric antigen receptor (CAR)-T cell outcomes and toxicities have yet to be fully explored. In a retrospective study at UCLA, we explored the association between CHIP and clinical outcomes of 68 adult patients with MM (31% with CHIP mutations) who were undergoing CAR-T cell therapy from 6/1/2021 to 12/31/2024. The overall (95% CHIP vs. 93% no CHIP; p = 0.99) and complete response rates (81% CHIP vs. 67% no CHIP; p = 0.15) did not differ by CHIP status. Similarly, CHIP mutations did not impact progression-free survival (HR 0.83; 95% CI 0.38–1.83; p = 0.65) or overall survival (HR 0.76; 95% CI 0.24–2.45; p = 0.65). Patients with CHIP mutations were more likely to develop CRS (100% vs. 70%; p = 0.007); however, there was no difference in the incidence of ICANS (33% CHIP vs. 17% no CHIP, p = 0.20). Our results show that although CHIP did not negatively influence response rate, complete response rate, survival, or progression-free survival in MM patients after CAR-T cell therapy, it did confer a higher risk of inflammatory response with increased frequency and grade of CRS.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s12185-026-04249-4.
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BibTeX
@article{carlson2026impact,
title = {{Impact of clonal hematopoiesis of indeterminate potential on treatment outcomes in multiple myeloma patients undergoing CAR-T cell therapy}},
author = {Sophie G. Carlson and Benjamin R. Puliafito and Kosuke Kawai and T. Niroshi Senaratne and Thomas D. Lee and Tasha Lin and John Timmerman and Sarah M. Larson},
journal = {International Journal of Hematology},
year = {2026},
month = jul,
doi = {10.1007/s12185-026-04249-4},
url = {https://doi.org/10.1007/s12185-026-04249-4},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Impact of clonal hematopoiesis of indeterminate potential on treatment outcomes in multiple myeloma patients undergoing CAR-T cell therapy
AU - Sophie G. Carlson
AU - Benjamin R. Puliafito
AU - Kosuke Kawai
AU - T. Niroshi Senaratne
AU - Thomas D. Lee
AU - Tasha Lin
AU - John Timmerman
AU - Sarah M. Larson
PY - 2026
DA - 2026/07/18
JO - International Journal of Hematology
DO - 10.1007/s12185-026-04249-4
UR - https://doi.org/10.1007/s12185-026-04249-4
AB - Clonal hematopoiesis of indeterminate potential (CHIP) is the presence of hematologic malignancy-associated somatic mutations in patients without hematologic malignancies. In multiple myeloma (MM), the implications of CHIP on chimeric antigen receptor (CAR)-T cell outcomes and toxicities have yet to be fully explored. In a retrospective study at UCLA, we explored the association between CHIP and clinical outcomes of 68 adult patients with MM (31% with CHIP mutations) who were undergoing CAR-T cell therapy from 6/1/2021 to 12/31/2024. The overall (95% CHIP vs. 93% no CHIP; p = 0.99) and complete response rates (81% CHIP vs. 67% no CHIP; p = 0.15) did not differ by CHIP status. Similarly, CHIP mutations did not impact progression-free survival (HR 0.83; 95% CI 0.38–1.83; p = 0.65) or overall survival (HR 0.76; 95% CI 0.24–2.45; p = 0.65). Patients with CHIP mutations were more likely to develop CRS (100% vs. 70%; p = 0.007); however, there was no difference in the incidence of ICANS (33% CHIP vs. 17% no CHIP, p = 0.20). Our results show that although CHIP did not negatively influence response rate, complete response rate, survival, or progression-free survival in MM patients after CAR-T cell therapy, it did confer a higher risk of inflammatory response with increased frequency and grade of CRS. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s12185-026-04249-4.
SN - 0925-5710
SN - 1865-3774
ER -