Clonal Hematopoiesis in Newly Diagnosed Multiple Myeloma: Associations With Neutropenia, Supportive Care Burden, and Survival

BACKGROUND: Clonal hematopoiesis (CH) is increasingly recognized as a clinically relevant host factor in newly diagnosed multiple myeloma (NDMM), with potential implications for frailty, treatment tolerance, supportive care burden, and overall survival (OS). MATERIALS AND METHODS: We retrospectively analyzed 181 patients with NDMM whose diagnostic bone marrow specimens were evaluated using targeted next-generation sequencing (NGS). Clinical data were abstracted from electronic records and paper charts. Associations between CH and treatment-related cytopenias, supportive care requirements, recurrent infections, and OS were evaluated using logistic regression and Cox proportional hazards models. RESULTS: The mean age was 69 years 58% were male, first-line induction consisted mainly VCd (n = 109, 60.2%) or VRd (n = 54, 29.8%) and CH was identified in 77 patients (42.6%). CH was associated with neutropenia at diagnosis (P = .023), during first-line treatment (P < .001), and during maintenance therapy (P = .009), as well as erythrocyte transfusion support (P < .001), recurrent infections (P = .027), and granulocyte colony-stimulating factor (G-CSF) use (P < .001). In multivariable analyses, CH was independently associated with neutropenia during first-line treatment (odds ratio [OR]: 4.4, P < .001) and maintenance therapy (OR: 6.7, P = .003), recurrent infections (OR: 2.5, P = .041), erythrocyte transfusion support (OR: 3.8, P = .006), and granulocyte colony-stimulating factor use (OR: 2.2, P = .026). CH was also independently associated with inferior OS (hazard ratio [HR]: 1.7, P = .036), with a similar adverse association among patients harboring at least 2 CH mutations (HR: 1.9, P = .032). CONCLUSION: CH was associated with baseline and treatment-related cytopenias, greater supportive care requirements, recurrent infections, and inferior OS, supporting its potential clinical relevance for cytopenia risk stratification and supportive-care planning during contemporary multiple myeloma therapy.