Impact of clonal hematopoiesis of indeterminate potential on treatment outcomes in multiple myeloma patients undergoing CAR-T cell therapy.

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.