Multiple myeloma in the real-world practice: clinical and prognostic indeces - single center experience

The Second Revision of the International Staging System (R2-ISS) is an prognostic model established in newly diagnosed multiple myeloma (NDMM) patients as a marker of disease-related biological risk. Still, the course of disease is influenced by patient-related factors as well. The International Myeloma Working Group (IMWG) frailty score provides a standardized assessment of patient fitness and may complement biological risk stratification. The aim of study was to analyze prognostic significance of R2-ISS scoring system and IMWG frailty status in NDMM patients (pts) within RWE settings of the routine clinical practice.

Analyzed group included 371 NDMM patients (pts, 184 males/187 females, median age 62.9 years, range 36-88) diagnosed between 2018 and 2025. Patients were stratified at the time of diagnosis according to the ISS, R-ISS, R2-ISS, and the original IMWG frailty score. Treatment response and follow-up were assessed according to the IMWG response criteria and EHA-EMN recommendations. Differences in progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier method and log-rank test. Independent OS predictors were identified using the Cox proportional hazards regression model.

Treatment response (≥PR) was achieved in 275 of 340 evaluable patients (80.9%). Increasing R2-ISS stage was associated with a lower probability of achieving treatment response (p=0.027), while frailty independently correlated with inferior response rates (p<0.001). Both PFS (p < 0.001) and OS (p < 0.001) was significantly shorter in patients with higher R2-ISS stages. In accordance to the IMWG frailty score, fit patients had significantly durable PFS (p<0.001) and the OS (p <0.001). Importantly, the composite classification integrating R2-ISS and IMWG frailty score provided additional discrimination of OS (p<0.001). Multivariate model for OS pointed out most significant impact of frailty status (p<0.001), followed by treatment response categories (p<0.001), and R2-ISS (p=0.009).

R2-ISS and IMWG frailty score provide complementary prognostic information in NDMM. Their combined assessment improves risk stratification beyond disease-related factors alone and may facilitate more individualized treatment planning in the routine clinical practice.