Fellow Weill Cornell Medicine Brooklyn, New York, United States
Introduction: Smoldering multiple myeloma (SMM) is a heterogeneous condition comprised of patients with varying risk of progression to multiple myeloma (MM). Existing models to predict the risk of progression to active disease are based on MM markers from a single time point at initial presentation without regard to marker evolution over time. In this study, we assessed the effect of dynamic temporal changes in the free light chain ratio (FLCr) on the risk of progression from SMM to MM.
Methods: We performed a retrospective analysis of patients diagnosed with SMM between 2002 and 2019 at Memorial Sloan Kettering Cancer Center with follow-up to 2022. Only patients with available FLCs (Freelite, The Binding Site) at diagnosis were included. Baseline laboratory, pathology, and imaging data, as well as date of diagnosis and progression, were manually reviewed. Progression from SMM to active MM was defined according to the diagnostic criteria at the time of progression or initiating treatment for active MM. Serial FLC levels between the date of diagnosis and progression were obtained by computerized extraction. We assessed the time to progression (TTP) using the Kaplan-Meier method, with log-rank tests for comparison between groups. We used Cox regression to estimate the risk of progression with hazard ratios (HRs) and 95% confidence intervals (CIs).
Results: A total of 398 patients were included with a median age of 64 years and 55% male. The median baseline FLCr was 9.8 (interquartile range 3.3-34.3). During a median follow-up time of 84 months, 184 patients (46%) progressed to active MM with a median TTP of 94 months. Patients were divided into quintiles based on the baseline FLCr (Q1-Q5). Patients in Q5 had a FLCr from 26.6-94.8 and had an increased risk of a progression (median TTP 36 [95% CI: 29-62] months, HR 3.2 [1.9-5], p< 0.001) when compared to patients in Q1. Patients in Q4 (FLCr 11.3-26.6) had a median TTP of 102 (53-not reached) months and a HR of 1.7 (0.9 -2.9). For patients in Q1-Q3 (FLCr 1-11.2), the median TTP ranged from 128 to 213 months, and HRs were similar for patients in Q3 and Q2 compared to Q1.
Patients were further stratified into groups based on the change in the FLCr at 1 year (ΔQ1-ΔQ5). Patients in ΔQ5 had a rise in FLCr (ΔFLCr) of >55% compared to their baseline. After 1 year, they had an increased risk of progression with a median TTP of 48 (21-116) months, and a HR of 2 (1.1-3.8) compared to patients in ΔQ1. Patients in ΔQ4 (ΔFLCr 17-55% increase from baseline) had a median TTP of 67 (39-not reached) months and a HR of 1.8 (0.9-3.3). For patients in ΔQ1-ΔQ3 (ΔFLCr < 17%), the median TTP ranged from 97 to 201 months. There was no significant difference in the HR for progression between patients in ΔQ3 and ΔQ2 compared to ΔQ1.
Conclusions: In addition to baseline risk stratification based on the FLCr, changes in FLCr within the first year of diagnosis provide additional prognostic information to further guide the management of patients with SMM.
