MM-361 The Prognostic Role and Utility of Highly Sensitive Minimal Residual Disease Assay in Multiple Myeloma: Is There Really a Difference?

Context: The role of higher-sensitivity minimal residual disease (MRD) assays in predicting survival outcomes and guiding treatment decisions remains to be validated in patients with multiple myeloma (MM). Objective: To determine the predictive and prognostic role of high-sensitivity next-generation sequencing (NGS) MRD assays in patients with MM undergoing autologous stem cell transplant (ASCT). Design: We performed a retrospective analysis on a cohort of patients diagnosed with MM between 2015 and 2020. All patients underwent front-line ASCT and were evaluated with an NGS MRD assay with a sensitivity of 10^–6 at day 100 post-ASCT. Main Outcome Measures: Given the retrospective nature of the study, we used the time to next treatment (TTNT) as a surrogate marker for progression-free survival. Overall survival (OS) was included as a secondary analysis. Results: A total of 186 patients were included in the analysis. With a mean follow-up time after ASCT of 30.2 months, patients who achieved MRD negativity at 10^–6 had longer TTNT than patients achieving negativity at 10^–5 or lower thresholds (HR: 0.289, 95% CI: 0.110–0.758, p=0.0116). On multivariable analysis, adjusting for the R-ISS stage, IMWG response category, and cytogenetic risk status, MRD negativity with a sensitivity of 10^–6 was the strongest prognostic factor for longer TTNT. MRD alone did not predict OS, which may be associated with the relatively limited follow-up time. Additionally, patients who achieved sustained MRD negativity, defined as negative MRD confirmed after 1 year, had significantly longer TTNT in both the univariate (HR: 0.07, 95% CI: 0.01–0.63, p=0.0175) and multivariable (HR: 0.0109, CI: 0.0003–0.4199, p=0.0153) models. At cutoff, of the 23 patients with sustained MRD negativity, 13 (57%) had been off therapy for a mean duration of 14 months after the second measurement with no documented progressions or deaths. Conclusions: Overall, MRD negativity at a sensitivity of 10^–6 was associated with a longer TTNT, regardless of induction therapy regimen or baseline characteristics. Higher-sensitivity MRD assays can help identify a subset of patients with very low disease burden who have a decreased risk of progression and could help guide therapy-related decisions, including treatment discontinuation.