MRD, Biomarkers in Multiple Myeloma

This article was originally published by AJMC

MRD Should Be More Widely Used in Clinical Care of MM, Report Argues

Advances in scientists’ understanding of multiple myeloma (MM) and in the ability to assess minimal residual disease (MRD) have made the metric an important method to track the efficacy of therapy in clinical trial settings. Yet, a number of questions remain about how exactly MRD can be used in day-to-day practice.

In an article in the Journal of Hematology & Oncology, corresponding author Jesús F. San-Miguel, MD, PhD, and colleagues discussed challenges to implementation of MRD in patients with MM. San-Miguel is a professor at the University of Navarra in Spain.

The authors explained that traditional methods of testing and defining success in the treatment of MM have become outdated in the new scientific paradigm. They noted that some patients in so-called complete remission (CR) are at a higher risk of progression than others, a problem that can be overcome with modern evaluations like MRD.

“Therefore, the words ‘complete’ [and] ’remission’ are misleading for many patients because they may interpret that, once [they have] achieved such status, the disease has been eradicated,” the authors wrote. “Thus, it becomes evident that more sensitive techniques are needed to detect measurable (formerly called minimal) residual disease persisting below CR.”

In advocating for broader use of MRD in a clinical setting, San-Miguel and colleagues wrote that MRD meets the criteria necessary for broad use.

MRD supersedes the prognostic value of CR, and MRD status appears to be reproducible in different settings and using molecular and immunophenotypic methods.

The techniques for ascertaining MRD can be broadly classified into 2 groups: those focused on finding extramedullary disease, such as positron emission tomography (PET)/CT scans, and those focused on detecting intramedullary disease, either multiparameter flow cytometry (MFC) immunophenotyping or molecular assessment of immunoglobulin gene rearrangements. Next-generation flow (NGF) cytometry and next-generation sequencing (NGS) each represent advances in techniques for detecting intramedullary disease, though the authors said these methods can lead to false-negatives.

“Thus, further improvement in the sensitivity of NGF and NGS are warranted to optimize risk stratification based on patients’ MRD status,” they wrote. “PET/CT is currently the optimal method to evaluate the disease outside the [bone marrow], and there are ongoing efforts for its standardization.”

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