Long term follow up of multiple myeloma patients achieving MRD negativity at 10 ^-6 .

e19549 Background: Achievement of deep responses in multiple myeloma (MM) has been associated with improved outcome and the regular assessment of minimal residual disease (MRD) has become the new standard in patient care. With the improvement of molecular assays, the sensitivity of MRD assessment has deepened to levels of 10 -6 and the achievement of MRD negativity at such levels has shown to predict for excellent long-term outcome. Yet, follow up in most studies has been short and there is a lack of understanding if and how other factors could influence the prognostic impact of MRD negativity. This retrospective, single-center study investigates the long-term outcome of MM patients that achieved MRD negativity at 10 -6 and investigate the impact of other meaningful clinical parameters, such as age, high-risk (HR) disease and treatment lines. Methods: Negative test results from any MM patient who had at least one negative MRD test at 10 -6 by Clonoseq between 2018-2024 were included, yielding a total of 726 samples from 271 patients. HR status was defined according to the IMS/IMWG consensus. Time to progression (TTP) and overall survival (OS) were calculated with Kaplan Meier Curves; multivariate analysis (MVA) was performed using Cox regression with a counting-process model. Results: Median age of the patient cohort was 64 years with 136 (51%) being male and 84 patients (31.5%) had HR disease. For 222 patients (83.2%), the MRD test was done during first line therapy, while in 27 patients (10%) the test was performed during second line and in the remaining 18 (7%) patients, MRD was performed in 3 rd or later lines. Median TTP for the whole cohort from time point of initial negative MRD test was not reached, but the 5-year TTP was 72.8%. 5-year OS was 82.1%. Median time from MM diagnosis to initial MRD negative test was 43 months for the whole cohort and 37 months for patients in 1 st line. For patients that progressed, the median time from last negative MRD test to next treatment was 18.5 months. 5-year TTP was significantly worse for HR patients (60% vs 79%) compared to non-HR patient, p=0.01. Furthermore, in MVA, a higher age (>60 years) and more than one treatment line were significantly associated with shorter progression free survival. Conclusions: Here we show that MM patients who achieve MRD negativity at 10 -6 have an excellent long-term outcome, yet MRD negative results should always be interpreted in the context of other clinical factors. Even among patients that achieve MRD-negativity at 10 -6 , IMWG risk, age and number of prior lines continue to have prognostic impact.