Overview
Functional high-risk multiple myeloma (FHRMM)—defined as disease progression or death within 18 months of initiating first-line therapy—occurs in a subset of newly diagnosed patients who are not fully identified by traditional cytogenetic risk models. This study analyzed 15,404 newly diagnosed patients in the US Flatiron Health Research Database to evaluate baseline attributes and outcomes associated with FHRMM.
Overall, 21% (n=3,209) of patients met FHRMM criteria. On multivariable analysis, FHRMM was associated with baseline features including poorer performance status, advanced stage, extramedullary disease, abnormal lab markers (hemoglobin, calcium, renal function, platelets), Black race, older age (≥75 years), and lower area-level socioeconomic status. Among patients with FHRMM, receipt of autologous stem cell transplant or quadruplet induction was associated with longer first-line real-world progression-free survival. FHRMM status was also associated with inferior post-progression survival.
Why this matters
These findings indicate that clinical factors, laboratory markers, and social determinants of health identified at diagnosis can help identify patients at risk for early progression beyond cytogenetic markers alone. Recognizing these features early may inform treatment selection and support clinical trial design for high-risk multiple myeloma.