Minimal residual disease dynamics in newly diagnosed multiple myeloma and impact on progression-free survival: A cohort study.

7570 Background: Minimal residual disease (MRD) is a sensitive tool for evaluating treatment response in multiple myeloma (MM) and is a surrogate marker of progression-free survival (PFS) and overall survival (OS). Consecutive MRD evaluations offer important information regarding the depth and the duration of response to treatment and can be used to guide the patients’ management. Methods: This single center, retrospective study included patients with newly diagnosed MM (NDMM), who were evaluated with at least 3 consecutive MRD tests. Four subgroups of patients were identified: sustained MRD positive (sMRDpos), sustained MRD negative (sMRDneg), converted to MRD negative (conMRDneg) and converted to MRD positive (conMRDpos). The aim of the study was to compare PFS between groups. Results: Overall, 335 NDMM patients were included in the analysis. The median age at diagnosis was 59 years (range 35-89), and the median number of assessments was 5 (range 3-14). Regarding risk stratification, 56 (16.7%) were ISS-3, and 52 (15.5%) were labeled as high-risk per the novel IMS/IMWG HRMM criteria. The median number of MRD evaluations in each patient was 5 (range 3-13). One third received quadruplet regimen. The median follow-up of the cohort was 6.1 years. Patient distribution according to MRD status was as follows: 191 (57%) sustained negativity, 40 (12%) sustained positivity, 53 (15.8%) converted to negative, whereas 51 (15.2%) converted to positive. Median PFS and OS were not achieved in any of the MRD subgroups. Sustained MRD negativity was associated with superior PFS compared to all the other subgroups (HR=0.21, 95% CI: 0.10 – 0.42, p<0.001). Sustained MRD positivity was associated with significantly inferior PFS compared to sMRDneg (HR=4.84; 95% CI: 1.91 – 12.30, p<0.001) and conMRDpos had also inferior PFS compared to the sMRDneg (HR= 6.04, 95% CI: 2.74 – 13.31, p<0.001). Furthermore, the presence of at least one MRD positive, at any time-point, was associated with inferior PFS compared to the sMRDneg (HR= 4.29, 95% CI: 2.05 – 8.99, p<0.001). Among the sustained MRD negative patients, high risk cytogenetics yielded a trend towards worse PFS (HR= 1.42. 95% CI: 0.30 - 6.69, p=0.659), possibly suggesting that sMRDneg overrides high risk cytogenetics. Finally, among the 165 patients who sustained MRD negativity, the median number of MRD tests were 5 (range 3-14). Among these patients with more than 5 tests had superior PFS, compared to less than 5, with a HR= 0.04, 95% CI: 0.01 – 0.33, p=0.003 signaling no further need of additional consecutive MRD testing in such patients. Conclusions: In patients with NDMM in the real-world setting, sustained MRD negativity is associated with prolonged PFS, even in HR patients, whereas the presence of even one MRD positive result impacted PFS.