Routine Evaluation of Minimal Residual Disease in Myeloma Using Next-Generation Sequencing Clonality Testing:...

Area of Science:

• Hematology
• Oncology
• Molecular Diagnostics

Background:

• International Myeloma Working Group guidelines recommend high-sensitivity methods for minimal residual disease (MRD) detection in multiple myeloma.
• Next-generation sequencing (NGS) offers high specificity and sensitivity for IGH gene rearrangements, but its clinical application and comparison to high-sensitivity flow cytometry (hsFC) are not well-documented.

Purpose of the Study:

• To describe the clinical use of NGS for IGH and IGK gene rearrangements in multiple myeloma.
• To compare the performance of NGS with hsFC for MRD detection and monitoring.
• To evaluate the prognostic value of MRD detection by NGS and hsFC.

Main Methods:

• A large, single-institution study analyzed 438 samples from 251 multiple myeloma patients.
• NGS was used for clonal characterization and monitoring of IGH and IGK gene rearrangements.
• Results were compared with hsFC for MRD detection and concordance analysis.

Main Results:

• NGS successfully characterized the index clone in 93.6% of patients, with success rates dependent on plasma cell cellularity.
• NGS detected MRD in 78.6% of monitoring samples.
• Concordance between NGS and hsFC was high (92.9%), with discordant cases involving low-level disease near assay detection limits.

Conclusions:

• NGS and hsFC demonstrate similar operational sensitivity for MRD detection in multiple myeloma.
• The choice between NGS and hsFC may be guided by practical rather than performance-based considerations.
• Both assays are valuable tools for MRD assessment, treatment response, and prognostication in multiple myeloma.