When Timing Matters Most: Early Relapse Outweighs Baseline Risk in Myeloma.

Multiple myeloma outcomes vary widely, with risk stratification typically based on baseline characteristics. Functionally high-risk multiple myeloma (FHRMM), defined by early relapse within 12 months of initial therapy or autologous stem cell transplant, is associated with poor prognosis. However, the continued prognostic impact of baseline high-risk features within the FHRMM cohort remains unclear. This study analyzed 181 FHRMM patients from the CoMMpass dataset, categorized into standard-risk (SRG) and high-risk (HRG) groups based on baseline cytogenetics and ISS stage. Despite SRG patients possessing more favorable baseline risk profiles, including lower SKY92 scores, their overall survival (OS) was not significantly different from HRG patients (20.7 vs. 18.1 months, p = 0.059). Treatment regimens and response rates were comparable between groups. Within the FHRMM cohort, only baseline ISS stage I retained prognostic significance for OS. In conclusion, FHR status overrides traditional baseline risk factors in determining prognosis. Patients experiencing early relapse should be considered uniformly high-risk, highlighting the need for effective salvage therapies and consideration of novel treatments like CAR T-cell therapies.