(PA-201) Delayed and Sustained Minimal Residual Disease Response Predicts Favorable Outcomes in Newly Diagnosed Multiple Myeloma

Minimal residual disease (MRD) negativity is a well-established prognostic marker in multiple myeloma (MM), yet the clinical relevance of the timing and duration of MRD response remains uncertain, especially among patients who never achieve MRD negativity.

Methods: In this large cohort study, we analyzed 1,048 newly diagnosed MM patients, encompassing 5,406 flow cytometry-based MRD assessments. We assessed the associations of time to best MRD response and duration of MRD response with progression-free survival (PFS) and overall survival (OS) using landmark and time-dependent analyses. Multivariable Cox regression models were used to evaluate the prognostic impact of MRD response kinetics across clinical and genetic risk factors.

Results: A longer time to best MRD response ( >6 months) was significantly associated with improved PFS and OS, particularly in patients who never achieved MRD negativity but exhibited persistent low-level disease. Early responders were more likely to have higher tumor burden and high-risk cytogenetic abnormalities. Importantly, a prolonged MRD duration (≥36 months) predicted favorable outcomes regardless of MRD status, cytogenetic risk, or transplant eligibility. Patients with a “Late + Long” MRD pattern exhibited the best long-term outcomes, including those who never achieved MRD negativity.

Conclusions: Our findings demonstrate that MRD kinetics—specifically the timing and duration of response—have independent prognostic value beyond static MRD negativity. A slow but sustained MRD response may offset the adverse impact of MRD positivity or high-risk features and could inform long-term disease monitoring and individualized treatment strategies.