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

Abstract

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). 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). 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. 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. 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. 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.