MRD in multiple myeloma: Moving from "minimal" to "measurable"

Area of Science:

• Hematology
• Oncology
• Molecular Diagnostics

Background:

• Minimal residual disease (MRD) is a key prognostic factor in hematologic malignancies like multiple myeloma (MM).
• Historically, MRD was defined by undetectable cancer cells; it is now recognized as measurable residual disease (MRD), emphasizing its quantitative and actionable nature.
• Advanced techniques like next-generation flow cytometry and sequencing allow MRD detection at very high sensitivities (10^-6-10^-7).

Purpose of the Study:

• To review the methodologies for detecting MRD in multiple myeloma.
• To discuss clinically relevant thresholds for MRD assessment.
• To highlight the therapeutic implications and the shift towards measurable residual disease.

Main Methods:

• Review of current literature on MRD detection in multiple myeloma.
• Analysis of next-generation flow cytometry and sequencing technologies.
• Discussion of regulatory acceptance and clinical utility of MRD negativity.

Main Results:

• Achieving MRD negativity is a strong predictor of improved survival in both newly diagnosed and relapsed/refractory MM.
• MRD negativity is increasingly used as an endpoint for accelerated drug approval by regulatory agencies.
• Despite advances, challenges in assay sensitivity, standardization, and result interpretation persist.

Conclusions:

• The concept of MRD in multiple myeloma has evolved to measurable residual disease, reflecting its clinical importance.
• MRD assessment is vital for prognosis and treatment decisions in multiple myeloma.
• Continued efforts are needed to standardize MRD assays and optimize their interpretation for improved patient outcomes.