Prognostic value of MRD dynamics in NDMM

Results from a translational study evaluating the prognostic significance of measurable residual disease (MRD) dynamics in patients with newly diagnosed multiple myeloma (NDMM) were published in Blood by Gonzalez et al. MRD dynamics were computed using next-generation flow (NGF) cytometry across 3,610 assessments from 539 patients enrolled in the GEM2012MENOS65 (NCT01916252)/GEM2014MAIN (NCT02406144) and GEM2017FIT (NCT03742297) trials who had ≥3 MRD assessments. Findings were validated in 249 patients with NDMM treated in routine practice.

Key data: MRD dynamics identified five subgroups with distinct survival outcomes. Patients with late/sustained MRD response had 6-year progression-free survival (PFS) and overall survival (OS) rates of 81.5% and 94.1%, respectively, compared with 76.6% and 85.9% in patients with an early/sustained MRD response (p ≥ 0.05). Patients with volatile MRD had 6-year PFS and OS rates of 11.3% and 76.5%, respectively, while those with resurgent/persistent MRD had rates of 4.3% and 67.5%, respectively. These survival patterns were validated in the real-world cohort. MRD dynamics demonstrated greater prognostic discrimination for PFS than the Revised International Staging System (R-ISS) (C-index, 0.87 vs 0.64), while transplant eligibility had no independent prognostic value; similar findings were observed in the real-world cohort.

Key learning: Longitudinal MRD dynamics identified clinically distinct subgroups of patients with NDMM and demonstrated prognostic value for disease progression in both clinical trial and routine-practice settings.