EARLY RELAPSE WITHIN 18 MONTHS (ER18) IS A POWERFUL DYNAMIC PREDICTOR FOR PROGNOSIS AND COULD REVISE STATIC RISK DISTRIBUTION IN PATIENTS WITH NEWLY‐DIAGNOSED MULTIPLE MYELOMA

Abstract

The duration of response to treatment is a major prognostic factor and early relapse (ER) strongly predicts inferior survival in multiple myeloma (MM) patients. But the definitions of ER in MM varied from study to study. In this study, we aimed to identify the best ER timepoint which we integrated with initial traditional risk features to formulate a novel prognostic classification incorporating both static and dynamic risk. The study was based on the National Longitudinal Cohort of Hematological Diseases in China (NCT04645199) and a total of 629 patients diagnosed with NDMM were included in this study. We first summarized all studies about ER published to date and found that relapse within 18 months from the initial treatment or within 12 months from SCT was mostly used to define early PD in many studies. Our findings indicate that ER18 could effectively balance the bias of ER definitions for patients with or without ASCT, as well as fulfill all requirements for a dynamic risk predictor. The ER18 population (114/587; 19.4%) presented with more aggressive biologic features compared to a reference cohort (P < 0.001), with a significant short median overall survival (OS) of 28.9 months. We also described the specific transitions from static risk profile to dynamic risk distribution in our cohort and then constructed a mixed-risk pattern to identify four novel populations with distinct survival outcomes (P < 0.001). A total of 367 (67.0%) patients presented with at least one high-risk feature: those with ISS III stage, elevated LDH, and HRCAs were classified as baseline high-risk (BHR) group; 86 (23.4%) patients experienced ER18 and further defined as mixed high-risk (MHR) population, and the remaining patients were classified as static high-risk (SHR). Within patients without BHR features, the dynamic risk event (ER18) occurred in 21(11.6%) patients, defined as functional high-risk (FHR). As expected, the MHR population had the worst outcomes with a median OS of 25.9 months (P < 0.001). Of note, FHR patients had similar survival compared to SHR patients (OS: not reached vs. 71.4 months; P = 0.235; Figure 3B), supporting the importance of dynamic risk factor (ER18) as a prognostic factor and further suggesting that lack of durable response could exert an adverse impact on prognosis similar to baseline high-risk variables. Moreover, we confirmed that ER18 refined the predictive accuracy of the Revised International Staging System stage (R-ISS). Encore Abstract - previously submitted to EHA 2023 Keywords: Diagnostic and Prognostic Biomarkers, Multiple Myeloma, Risk Models No conflicts of interests pertinent to the abstract.