Minimal Residual Disease in Myeloma: Application for Clinical Care and New Drug Registration

Abstract

The pace of advances in targeted and immune therapies in Multiple Myeloma (MM) is unprecedented.To keep this momentum going, a framework is proposed outlining key elements and regulatory considerations that will delineate how Minimal Residual Disease (MRD) data could be collected to help standardize correlative analyses across clinical studies. The framework is intended for use by sponsors to incorporate into ongoing or planned trials, without compromising or interrupting their primary trial objectives. Also covered are technologies already impacting MRD assessment in myeloma and emerging approaches that sponsors should consider including in their trials. The current value of MRD to inform clinical care is presented using real world cases of patients with smoldering MM, newly diagnosed transplant eligible and ineligible, and relapse refractory disease, with each case summarizing what is known and questions to be addressed in clinical studies.Research.

Minimal Residual Disease in Multiple Myeloma—Current Approaches and Future Clinical Implications

“…As techniques for MRD have been refined, most MCF protocols include ≥8 colors for surface and intracellular antigen, and there has been an effort to standardize and validate MCF protocols across institutions and countries. This has resulted in increasing levels of sensitivity, and per the most recent IMWG guidelines, labs that report MRD by MCF should be able to detect a minimum sensitivity of 10 −5 and up to the current highest sensitivity of 2 × 10 −6 [25].…”

“…The International Myeloma Working Group (IMWG) published a white paper in 2016 with the definitions and recommendations for MRD assessments (Table 1) [23,24]. The minimum sensitivity level recommended by Hemato 2022, 3 455 the IMWG is the detection of 1 neoplastic cell in 100,000 (10 −5 ) cells, while 1-2 cells in 1,000,000 (10 −6 ) is ideal [23,25]. The IMWG recommends MRD assessment in the bone marrow using multicolor flow cytometry (MCF) or next-generation sequencing (NGS).…”

“…The IMWG recommends MRD assessment in the bone marrow using multicolor flow cytometry (MCF) or next-generation sequencing (NGS). The IMWG is agnostic as to which method is used as long as it is validated for the specific sensitivity level [25]. These two methods, MCF and NGS, have separate benefits and pitfalls, which are discussed in this review.…”

Real‐world data on prognostic value of measurable residual disease assessment by fragment analysis or next‐generation sequencing in multiple myeloma

“…Treatment advances in multiple myeloma (MM) increased the proportion of patients achieving complete response (CR) over the past decades 1‐3 . This progress prompted an evolution of the definition of response, and measurable residual disease (MRD) testing is now being recognized as a strong and dynamic prognostic indicator in MM 4‐11 .…”

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Treatment advances in multiple myeloma (MM) increased the proportion of patients achieving complete response (CR) over the past decades. [1][2][3] This progress prompted an evolution of the definition of response, and measurable residual disease (MRD) testing is now being recognized as a strong and dynamic prognostic indicator in MM. [4][5][6][7][8][9][10][11] In this regard, MRD has been incorporated into the International Myeloma Working Group (IMWG) response criteria and is being developed as a clinical end-point in reports of trial outcomes.

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