P-095: Evolving M-spike and Risk of Progression in Smoldering Multiple Myeloma

Introduction: Current risk scoring systems for smoldering multiple myeloma (SMM) are based on disease burden where patients with M-spike >2 g/dL, bone marrow plasma cells >20%, and free light chain ratio >20 are deemed at high risk for progression. Here, we assessed information on the dynamics of the M-spike concentration for predicting progression to multiple myeloma (MM).

Methods: We analyzed all patients with SMM managed at Memorial Sloan Kettering Cancer Center between 2002-2019 with follow up to 2022. Descriptive statistics, Kaplan Meier curves, and Cox regression were used to analyze the risk of progression in relation to baseline M-spike and change in M-spike concentration. Disease progression was defined as fulfilling CRAB criteria and/or starting treatment for MM. Patient who progressed within the first 3 months of SMM diagnosis were excluded.

Results: We included 398 patients with SMM, 55% men and median age was 63.6 years. The median baseline M-spike level was 1.3 g/dL. Patients were stratified into quintiles with the highest risk of progression seen in quintile 5 (Q5), i.e. baseline M-spike of >=2.2 g/dL, where the median time to progression (TTP) was 29 months (95% confidence interval [CI] 24-64 months). The TTP for patients in Q4, i.e. M-spike of 1.6-2.2 g/dL, was 67 months (95% CI 51-115 months). The TTP was longer for patients with lower M-spike and was similar in Q1-3 (M-spike 0-1.6 g/dL) where the TTP ranged from 112-138 months.

During the first year of follow up, 11% of SMM patients progressed to MM. The rate of change (delta) in M-spike during year 1 of follow up translated into a higher risk of progression. In patients in the highest quintile of change (deltaQ5), delta M-spike of 0.3 g/dL or more during the first year, the median TTP was 22 months.

For SMM patients with baseline M-spike concentrations in Q5, the hazard ratio (HR) for progression to MM was 3 times higher (HR=2.9, 95% CI 1.8-4.6) compared to patients in Q1. Similarly, in SMM patients with the highest rate of change (deltaQ5), the HR was 2.9, (95% CI 1.6-5.4) compared to patients in deltaQ1 after year 1.

Interestingly, of the 11% (n=44) of patients who progressed during the first year, only 45% were in M-spike Q5 (n=20) at baseline. Of the remaining patients who progressed to MM during the first year of follow up, 9 were from baseline Q4 while 12 were from Q1-3, and 3 had no baseline M-spike.

Conclusions: In summary, we confirmed that a higher baseline M-spike was associated with a higher risk of progression from SMM to MM. However, among patients who progressed at year 1 of follow up, 55% were not in the baseline Q5 M-spike group. Furthermore, we found that patients with a high rate of change in M-spike during the first year had a similar rate of progression to MM compared to SMM patients with a high baseline M-spike. Thus, both burden of disease and disease biology reflected in a rapid change in M-spike should be considered when predicting the risk of progression in patients with SMM.