P-176: Predictors of unsustained measurable residual disease negativity in transplant-eligible patients with newly diagnosed multiple myeloma

Introduction: Most transplant eligible NDMM patients can achieve bone marrow MRD negativity after standardized treatment, but how to maintain long-term MRD-negative status after achieving MRD negativity is a current challenge. The aim of this study was to identify predictive factors for the reappearance of MRD in transplant-eligible patients with NDMM who had achieved bone marrow MRD negativity.

Methods: We retrospectively analyzed data from transplant-eligible NDMM patients who had been detected as MRD-negative by two-time multiparametric flow cytometry tests. Regular and dynamic bone marrow MRD monitoring was performed at our center, and patients were monitored at the end of induction and every 3 to 12 months after transplantation.

Results: Out of 390 enrolled patients, 261 (66.9%) achieved MRD negativity. The median age was 55 years, with 70.1% of patients being R-ISS stage II-III. The median time to MRD-negative was 10.3 months. After a median follow-up of 27 months, 37.2% of patients lost MRD-negative status. Among these patients, 28.9% had maintained 3 years of persistent MRD negativity. Additionally, 47.4% of patients had a positive MRD test result before biochemical or clinical progression. The median time from MRD positivity to a progression survival event (progressive disease or death) was 11.4 months.HRCA ≥1, PLT < 100*10^9/L, and reaching first MRD negativity after the start of maintenance were significant predictors of failure to maintain MRD negativity. Maintenance therapy, such as lenalidomide, bortezomib + dexamethasone, and daratumumab, reduced the risk of MRD reappearance compared with thalidomide/interferon administration.

Conclusions: This study highlights the factors that contribute to the reappearance of MRD in transplant-eligible NDMM patients and emphasizes the importance of early attainment of MRD-negative status and maintenance therapy options to maintain long-term MRD negativity.