Prognostic impact of early disease progression and early mortality in patients with multiple myeloma: a real-world cohort study

Introduction Multiple myeloma (MM) is a clinically heterogeneous malignancy in which outcomes remain difficult to predict using static baseline risk models. Increasing attention has shifted toward dynamic prognostic markers, including early disease progression and early mortality; however, their relative prognostic value—particularly the optimal definition of early progression—and their integration with patient-related factors remain insufficiently defined in real-world populations. Methods We retrospectively analysed 207 newly diagnosed MM patients treated between 2018 and 2023. Early disease progression was defined as progression within 18 (POD18) and 24 months (POD24) from treatment initiation. Early mortality was defined as death within six months of diagnosis. Overall survival (OS) and progression-free survival (PFS) were analysed using Kaplan–Meier estimates and Cox regression models, including time-dependent analyses. Results During a median follow-up of 60 months, POD18 occurred in 44.0% and POD24 in 51.2% of patients. POD18 was strongly associated with inferior OS (HR 9.38; 95% CI 5.98–14.70; p 0.0001) and demonstrated superior prognostic discrimination compared with POD24 (C-index 0.742 vs. 0.719). In multivariable analysis, POD18 remained the strongest independent predictor of OS, alongside comorbidity burden and performance status. Early mortality occurred in 17.9% of patients and was independently associated with advanced disease stage. Time-dependent modelling showed that the prognostic impact of baseline staging decreased over time, supporting the dynamic nature of risk in MM. Conclusion POD18 is a robust and clinically informative dynamic prognostic marker that outperforms POD24 in predicting survival in real-world patients with MM. Integration of early disease kinetics with baseline disease burden and comorbidity burden provides a pragmatic framework for dynamic risk stratification, particularly in settings with limited access to comprehensive molecular profiling.