Minimal residual disease in multiple myeloma: why, when, where

Abstract

Improvements in multiple myeloma therapy have led to deeper responses that are beyond the limit of detection by historical immunohistochemistry and conventional flow cytometry in bone marrow samples. In parallel, more sensitive techniques for assessing minimal residual disease (MRD) through next-generation flow cytometry and sequencing have been developed and are now routinely available. Deep responses when measured by these assays correspond with improved outcomes and survival. We review the data supporting MRD testing as well as its limitations and how it may fit in with current and future clinical practice.

Graphical abstract

Figure 1.

Progression-free survival according to MRD level at the start of maintenance in IFM 2009. Progression-free survival improves with each log reduction in MRD in IFM 2009 in patients who achieved at least a very good partial response. Figure adapted from Perrot et al.

Figure 2.

Examples of trials evaluating MRD to guide treatment. Treatment decisions with MRD may be broadly divided into 2 categories: (A) following initial therapy to guide treatment intensification or consolidation in patients with MRD positive disease or (B) in patients on maintenance therapy, to guide discontinuation of treatment. Some trials are also examining “early” initiation of therapy with the appearance of MRD-positive disease. D, dexamethasone; isa, isatuximab; K, carfilzomib; maint, maintenance; PD, progressive disease; PREDATOR, Pre-emptive Daratumumab Therapy of Minimal Residual Disease Reappearance or Biochemical Relapse in Multiple Myeloma; R, lenalidomide; RADAR, Risk-Adapted Therapy Directed According to Response; REMNANT, Relapse from MRD Negativity as Indication for Treatment; V, bortezomib.

Figure 2.

Examples of trials evaluating MRD to guide treatment. Treatment decisions with MRD may be broadly divided into 2 categories: (A) following initial therapy to guide treatment intensification or consolidation in patients with MRD positive disease or (B) in patients on maintenance therapy, to guide discontinuation of treatment. Some trials are also examining “early” initiation of therapy with the appearance of MRD-positive disease. D, dexamethasone; isa, isatuximab; K, carfilzomib; maint, maintenance; PD, progressive disease; PREDATOR, Pre-emptive Daratumumab Therapy of Minimal Residual Disease Reappearance or Biochemical Relapse in Multiple Myeloma; R, lenalidomide; RADAR, Risk-Adapted Therapy Directed According to Response; REMNANT, Relapse from MRD Negativity as Indication for Treatment; V, bortezomib.