MRD? We’re Aware of It, Say Oncologists, But We Don’t Use It for Decisions

A new survey shows the concept of measurable, or minimal, residual disease (MRD) in multiple myeloma (MM) has made its way to the provider level, but the report also found most clinicians are not using the metric to guide their decision-making.

Investigators from the University of Chicago Medical Center wanted to better understand whether and how clinicians are using MRD when they treat patients with MM. They noted that the development of methods such as multiparameter flow cytometry (MFC) and next-generation sequencing (NGS) to measure MRD have led to better predictions of patient survival, but said its use as a clinical decision-making tool remains unproven.

The authors constructed a survey, the results of which were published in the British Journal of Haematology. A total of 84 respondents completed the survey between September and November of 2018. Just over half (55%) took the survey prior to the FDA's approval of an NGS assay for MRD in MM. Most of the respondents (75/84) worked at academic medical centers, and the median clinical experience was 16 years.

The survey responses showed that all respondents were familiar with the concept of MRD, and 91% said they assess MRD in either clinical trial (80%) or standard-of-care (80%) settings. However, only 37% said they had made treatment decisions based on MRD assessments.

Benjamin Derman, MD, an assistant professor of medicine at the University of Chicago Medical Center and the study’s corresponding author, told The American Journal of Managed Care® that the 37% data point was higher than expected given the lack of evidence to guide the use of MRD in decision-making. He said that number might be due to the high proportion of academic clinicians in the survey.

“Altogether, this emphasizes the need for clinical studies designed to use MRD as a clinical decision-making tool,” he said. “For example, studies looking at the de-escalation of therapy in MRD-negative patients or the escalation of therapy in MRD-positive patients are worthwhile endeavors.”

The clinicians were roughly split in terms of which method they used to assess for MRD. Forty-nine percent said they preferred MFC (with depths ranging from 10^–4 to 10^–6). Forty-five percent said they preferred NGS, at a depth of 10^–6. The remaining 6% used PET/CT.

Asked when they perform the assessment, 62% said they do so during standard response assessment; 51% said at their first evaluation post-stem-cell transplantation; and 30% said after 1 or 2 years of maintenance therapy (30% for both time points).

Among those who said they assess for MRD:

• 71% respondents said the value provided by MRD includes prognostication
• 61% said it had value for future decision-making
• 51% said its value included prompting changes in duration of treatment
• 50% said it could be used as a surrogate endpoint in clinical trials
• 33% said it had value in determining potential changes to treatment.

Asked about any concerns they had about MRD, 54% identified not knowing when to do the assessment; 37% felt they didn’t know the utility of the assessment; and 34% raised concerns about the cost of testing. Derman and colleagues noted in the paper, however, that Medicare began to cover the ClonoSEQ NGS assay for MRD in January 2019, meaning more patients should now have access to the assessment at a depth of 10^–6.

Derman said he was struck by the variety among respondents in terms of the timing, modality, and depth at which they use MRD. Over time, though, he said he expects the paradigm to shift from using MRD not just as a prognostic tool, but also as a routine decision-making guide.

“That will include a shift towards a more routine deeper assessment of MRD with validated assays that are capable of detecting 1 abnormal plasma cell out of 1,000,000 nucleated cells in the bone marrow (so-called 10^^-6 limit of detection),” he said. “There are several ongoing studies that will likely help to speed up the adoption of MRD into a decision-making paradigm to optimize treatment for myeloma patients.”

Reference

Derman BA, Jasielec JK, Jakubowiak AJ. Clinician attitudes and practices toward measurable residual disease in multiple myeloma. Br J Haematol. 2020;190(3):470-472. doi:10.1111/bjh.16805