Debating the Use of MRD Testing for Treatment Decision Making

Laura Joszt

Although minimal residual disease (MRD) is increasingly being used to predict treatment outcomes and as a surrogate marker of progression-free survival, there remains controversy over whether it is ready to be used in treatment decision making.

There are some scenarios when having MRD information would make management decisions easier, according to an abstract from Jeffrey L. Wolf, MD, of the University of California, San Francisco.1 One scenario is when clinicians are deciding whether or not to stop maintenance therapy. There are likely many situations in which patients are being overtreated because patients stay on prolonged maintenance therapy until progression. These therapies not only are costly, but they also have side effects.

The knowledge that a patient has achieved MRD negativity year after year “would certainly help with the decision to stop therapy and not necessarily start another agent,” Wolf wrote.

In another scenario, rising MRD could indicate to clinicians that the current therapy was ineffective and should be stopped and that the patient should perhaps even switch to another therapy.

In both scenarios, Wolf noted that there would be no issue to use MRD in this way if only MRD was a peripheral blood test. However, MRD testing is currently a bone marrow test, which is why it is not used more. He argued that a bone marrow procedure should not stand in the way of MRD testing being used more.

Wolf added that MRD would be helpful for clinicians deciding whether to proceed with renal allografting—patients with persistent MRD negativity would do well to have the allograft, he wrote—or whether or not to transplant—negative MRD after induction could mean a patient does just as well going to maintenance therapy rather than being subjected to transplant first.

“I conclude that the time has come to begin to use MRD, along with other information, to make clinical decisions,” Wolf wrote.

However, in another abstract from the meeting, Thomas Martin, MD, of the University of California, San Francisco, argues that MRD testing has not realized its true potential yet in multiple myeloma.2

Martin agreed that blood-based testing would allow for greater use of MRD testing, but it is currently “not ready for primetime,” and, for now, MRD assessments should only be used to evaluate prognosis.

Some remaining important questions include how many cells are needed from the bone marrow biopsy to be an adequate sample. In addition, Martin noted that cross-study comparisons remain difficult as studies report MRD-negative results in different ways. For instance, some chimeric antigen receptor T-cell therapy studies label patients as MRD negative even when they have detectable m-proteins; however, this does not align with MRD negativity as defined by the International Myeloma Working Group.

“MRD results provide prognostic information only and future clinical trials with adaptive designs will define how MRD can guide treatment decisions,” Martin concluded.

1. Wolf JL. Debate: can MRD be used for treatment decisions? Yes!!! Clin Lymphoma Myeloma Leuk. 2019;19(suppl 1):S44-S45.
2. Martin T. Multiple myeloma: minimal residual disease testing—not ready for primetime. Clin Lymphoma Myeloma Leuk. 2019;19(suppl 1):S46-S48.
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