Real-world minimal residual disease assessment in multiple myeloma using a standardized flow cytometry approach: feasibility, clinical implications, and immune correlates from a single-center experience

Abstract

Minimal residual disease (MRD) assessment has emerged as a key prognostic marker in multiple myeloma (MM), with MRD negativity (undetectable MRD, uMRD) correlating with improved progression-free and overall survival. The International Myeloma Working Group recommends standardized protocols for MRD detection, including the EuroFlow-based next-generation flow cytometry (NGF), although its implementation in routine care remains challenging. We evaluated the feasibility and clinical utility of two CE-IVD-approved EuroFlow tubes for MRD detection in a real-world clinical setting, and investigated the relationship between bone marrow (BM) immune profiles and disease outcomes. Between December 2021 and February 2024, 74 MM patients (58 of them classified as transplant-eligible) underwent 97 MRD evaluations after achieving at least a very good partial response (VGPR). Using ≥2 million events/sample, a median sensitivity of 10⁻⁵ was achieved; 45% of cases were uMRD. After a median follow-up of 19 months, one relapse occurred in the uMRD group, whereas 15 relapses and 3 deaths were observed among persistent MRD (pMRD) patients. Immunophenotypic profiling revealed a higher granulocyte-to-lymphocyte ratio and a lower proportion of CD56dim NK cells, possibly reflecting immune rebalancing after bone marrow recovery. Our findings confirm the feasibility and prognostic relevance of NGF-based MRD detection using standardized commercial panels, and highlight the potential of immune profiling to provide additional biological insights into MRD dynamics in multiple myeloma.