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 a new report in the Journal of Hematology & Oncology, corresponding author Jesús F. San-Miguel, MD, PhD, and colleagues discuss 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The authors explained that traditional methods of testing and defining success in the treatment of MM have become outdated in the new scientific paradigm.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 achieved such status, the disease has been eradicated,” they 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 broadly be classified into 2 groups: those focused on finding extramedullary disease, such as PET/CT scans; and those focused 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.”

There are some pitfalls to MRD, however. One is the potential for false MRD-negative results due to sampling errors. The authors also reported that while an MRD-negative test result is a good prognostic sign, it bodes most well for patients when the negative result can be reproduced after 6 or 12 months.

To bring MRD testing into the clinic, the authors recommended that MRD assessment only be performed when a bone marrow aspirate is collected to confirm complete remission, and subsequently only when the results of the evaluation could be useful to make specific clinical decisions.

The authors noted that a number of different methods are being considered to evaluate MRD, but they said bone marrow samples remain the “gold standard.”

More broadly, San-Miguel and colleagues concluded that MRD is not only important for its prognostic value but also because it will better enable precision medicine in an era of rising drug costs.

“We have experienced great progress and now we need to optimize the use of highly effective drugs developed including immunotherapeutics,” the authors concluded. “This should be implemented early in the course of the disease in order to overcome the poor prognosis of high-risk patients, including those with persistent MRD after optimal frontline treatment.”

Reference

Burgos L, Puig N, Cedena MT, et al. Measurable residual disease in multiple myeloma: ready for clinical practice?.J Hematol Oncol. Published online June 22, 2020. doi:10.1186/s13045-020-00911-4