Role of Minimal Residual Disease Monitoring in Guiding Maintenance Therapy for Multiple Myeloma

Abstract

Background: Complete response by conventional serologic and morphologic criteria no longer separates multiple myeloma patients with durable remission from those destined to relapse, and measurable residual disease (MRD) testing has emerged to recover that lost prognostic resolution.

Objective: To synthesize published evidence on MRD detection methods, the prognostic and surrogate value of MRD negativity, and the use of serial MRD results to guide the duration and intensity of post-induction maintenance therapy.

Methods: Narrative synthesis of peer-reviewed literature on next-generation flow cytometry, next-generation sequencing, MRD meta-analyses and surrogacy analyses, and prospective MRD-adapted maintenance trials in newly diagnosed multiple myeloma.

Findings: EuroFlow next-generation flow and immunoglobulin-sequencing assays now detect residual clones below 10^-6 and predict progression-free and overall survival more sharply than complete response; trial-level surrogacy analyses link MRD-negativity gains to progression-free survival gains (R² approximately 0.70); and MRD-adapted trials including MASTER, AURIGA, FORTE and ATLAS show that stopping therapy in sustained MRD-negative patients and intensifying it in persistently MRD-positive patients each changes outcomes.

Conclusions: MRD status is prognostically validated and increasingly surrogate-validated; the remaining barriers to MRD-guided maintenance are trial maturation, serial-testing infrastructure and reimbursement rather than unresolved biology.