Targeted and immune therapies to treat multiple myeloma (MM) are advancing rapidly, and minimal residual disease (MRD) negativity is possible across the disease spectrum. MRD may be a surrogate endpoint for patient outcomes in clinical trials. A recent article in Clinical Cancer Research provides a framework for collecting and analyzing MRD data in the context of patient care, clinical trials and regulatory drug approval.

Newer treatments have led to deeper responses for patients with MM, and traditional measures complete response (CR) are not fully representative of disease control. Nearly all patients relapse despite achieving CR.

Previously, the International Myeloma Working Group (IMWG) added MRD assessment as a level of response based on data showing the prognostic value of MRD negativity.

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Measuring MRD

Next-generation sequencing (NGS) and next-generation flow (NGF) are most commonly used to measure bone marrow MRD. These tools allow for real-time detection and monitoring of MRD in clinical trials.

The preferred imaging tool to evaluate tumor metabolic activity and response to therapy is 18fluorodeoxyglucose (FDG)-PET. PET/CT is also used to assess residual disease outside of bone marrow.

Newer methods with liquid biopsy-based assays and mass spectrometry are in development.

The FDA has issued some guidance for clinical trial sponsors looking to use MRD as a biomarker for patient selection, stratification, as an endpoint, or to guide treatment decisions. For now, investigators can choose the method to measure MRD.

MRD Potential in Practice

Patients who achieve MRD negativity at any stage of the disease have a better outcome than patients who do not achieve MRD negativity.

In the analysis, the authors described case studies of patients with different stages of MM and what is known about applying MRD status to those patients:

  • Smoldering myeloma. MRD testing currently is only performed within clinical trials for patients with smoldering myeloma. More research is needed to understand the association between MRD negativity and progression-free survival.
  • Newly diagnosed MM. MRD status after induction therapy may help guide decisions for stem cell transplantation and maintenance therapy for standard-risk patients. However, no definitive data are available yet on whether MRD negativity predicts long-term outcomes after transplant. High-risk patients have better outcomes when they achieve MRD negativity, which may help inform decisions for continuing treatment.
  • Relapsed/refractory MM. Research is still evaluating MRD negativity as a surrogate endpoint that can predict outcomes in relapsed or refractory disease.

With more understanding of MRD, negativity may be used to guide real-world care decisions. Clinical trials may also be able to consider MRD as a surrogate measure for patient outcomes.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Anderson KC, Auclair D, Adam SJ, et al. Minimal residual disease in myeloma: application for clinical care and new drug registration. Clin Cancer Res. Published online July 28, 2021. doi:10.1158/1078-0432.CCR-21-1059