意义未明克隆性造血对接受 CAR-T 细胞治疗的多发性骨髓瘤患者治疗结局的影响

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.