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.