Complementary Roles of Next-Generation Flow and Next-Generation Sequencing for Measurable Residual Disease Assessment...

Highly sensitive measurable residual disease (MRD) assays play a crucial role in predicting prognosis and guiding further treatment in multiple myeloma (MM). This study aimed to compare the diagnostic performance and clinical utility of next-generation flow (NGF)- and next-generation sequencing (NGS)-based MRD assays in patients with MM.

We evaluated 55 bone marrow (BM) aspirate samples from 41 MM patients for MRD. NGF-MRD was performed on fresh BM specimens in accordance with EuroFlow standard operating procedures, whereas NGS-MRD was conducted on archived BM DNA using the LymphoTrack^® IGH FR1 assay.

The MRD detection rates were 43.6% (24/55) for NGF-MRD and 29.1% (16/55) for NGS-MRD with 67.3% (37/55) concordance rate between two MRD assays, and correlation coefficient (ρ) was 0.506. The 3-year progression-free survival (PFS) estimates were 37.5% and 71.6% for the NGF-MRD-positive and -negative groups, respectively (P = 0.056), and 40.4% and 69.1% for the NGS-MRD-positive and -negative groups (P = 0.167). In patients who MRD-positive by either NGF or NGS, the 3-year PFS was 40.0%, whereas those negative by both assays exhibited 75.9% (P = 0.035). Revised International Staging System stage III (hazard ratio [HR], 3.30) and combined MRD positivity (HR, 3.01) were most strongly associated with PFS in univariate analysis.

Both NGF-MRD and NGS-MRD play critical and complementary roles in monitoring MRD in MM. Notably, even isolated MRD positivity detected by either method was associated with disease progression in certain cases, underscoring the importance of both MRD assays.