NEW YORK – More than half of oncologists said they used minimal residual disease (MRD) testing results to help guide treatment decisions for multiple myeloma patients, despite some concerns about the lack of data supporting the use of MRD to guide treatment according to the results of a survey published in Blood Cancer Journal this month.
The findings underscore the importance of ongoing research that will provide critical evidence supporting when MRD status can be used to intensify or de-escalate treatment for patients.
The survey included responses from 89 oncologists who treat multiple myeloma patients in academic and non-academic settings. It queried oncologists on their use and understanding of MRD testing in multiple myeloma and presented them with hypothetical clinical scenarios to assess how they might factor in patients' MRD status in specific situations. Through the responses, researchers hoped to better understand clinicians' attitudes toward MRD and how MRD status might impact their decision making.
They found that 64 percent of clinicians surveyed did test multiple myeloma patients for MRD, whether it was in a non-research clinical setting or for clinical trials. Of those that said they did not assess MRD, they cited several reasons, the most common being that it was unclear when to do such testing (22 percent), they didn't expect results to be actionable (19 percent), and test costs (16 percent).
Benjamin Derman, an assistant professor of medicine in the section of hematology and oncology at University of Chicago Medical Center, noted this survey was done in 2021.
"In my own personal practice, I felt like there were many times where the MRD result that I was looking at was influencing my decision making, and I had a feeling that it was similar amongst other clinicians," Derman said. "But when you go to conferences, it's always [said] that MRD is not ready to guide decision making, that there's no data to support it, and we need clinical trials to guide it. All of that is true, but we have this tool right now and the question is, 'Are people using it to guide their decision making?'"
MRD testing is typically used to monitor how patients are doing on a treatment, as MRD negativity after treatment is associated with longer survival, and to assess the risk of disease recurrence. For instance, when first next-generation sequencing-based MRD test for blood cancers Adaptive Biotechnologies' ClonoSeq was approved in 2018, the US Food and Drug Administration noted that the test should be used to "to assess the change in burden of disease during and after treatment."
In addition to ClonoSeq, earlier this year, Genetron Health announced it was selling its CE-marked Seq-MRD test in the European Union and other countries. The test is designed to detect the CDR3 regional sequence of the IgH/K/L gene in B-cell receptors in bone marrow samples of patients with B lymphocytic leukemia and multiple myeloma before and after treatment.
As MRD tests have become more accessible, researchers have also begun exploring the value of using MRD status to guide treatment. In a 2016 trial, researchers de-intensified chemotherapy treatment for acute lymphoblastic leukemia patients with undetectable MRD status and found it did not jeopardize their survival rate. Meanwhile, the outcomes for patients with intermediate and high levels of MRD improved with therapy intensification based on MRD status in that study.
In light of data like this, some physicians have begun considering MRD data when making treatment decisions for their patients, the survey findings suggest. The survey presented oncologists with several clinical scenarios involving hypothetical multiple myeloma patients at several different stages of treatment: those who had received initial induction treatment, those who had received a stem cell transplant, and patients in the maintenance therapy setting. Oncologists were then asked to indicate how their treatment would change based on a patient's disease risk and MRD status.
About 60 percent of oncologists said they would change at least one treatment decision based on an MRD result. However, patients' disease risk seemed to play a larger role in treatment decisions, with 78 percent of clinicians changing their decision based on a patient having high or low disease risk, while 54 percent of respondents used both MRD status and the patient's disease risk to guide their decisions.
The scenario under which most respondents changed their answer based on MRD status, Derman noted, was a situation where a multiple myeloma patient was on maintenance therapy and had sustained MRD negativity. About 40 percent of respondents said they would discontinue treatment if the patient was MRD negative.
Even among clinicians who said there is no data supporting MRD status to guide decision making, about half changed their treatment decision in at least one clinical scenario based on the MRD result.
"In some ways, this confirmed our suspicion from the get-go, which is that MRD testing has this subtle influence on decision making," Derman said. "If you are somebody who is measuring it and using it for prognosis, you may not realize that it's actually affecting your decision making." This makes it even more important, he noted, to do the clinical trials to provide definitive evidence on how MRD status should inform treatment decisions, he concluded.
While the respondents in this survey were largely from academic cancer centers, about a quarter of respondents were from private practice or a hybrid academic-community practice. Derman said it is more difficult to identify trends in the smaller non-academic group but noted that clinicians there were evenly split between those who do assess MRD and those who don't.
Among all clinicians surveyed who said they tested for MRD, Derman said half ordered NGS testing and half ordered flow cytometry testing to determine MRD status. He noted that there are additional challenges to MRD testing in the community or private practice setting, especially for doctors who only have access to flow cytometry, which requires a fresh bone marrow biopsy sample for testing.
"Part of the issue with assessing MRD in private practice and among community physicians is whether they have a reliable test," Derman said. "That's where the next-generation sequencing testing comes in … because it's a centralized test and you don't need a fresh sample; it can be frozen and shipped." For these reasons, he suspects there appears to be more willingness among private practice clinicians to adopt NGS-based MRD testing.
As MRD testing adoption increases among oncologists, more studies are underway exploring the use of MRD to guide treatment. For example, Derman is leading a trial at his institution, called MRD2STOP, that is evaluating whether patients who are on post-transplant maintenance therapy and are MRD-negative can safely and effectively discontinue treatment. The investigators are following these patients who discontinued treatment for three years to track molecular changes in MRD status and survival.
In another Phase III study, the SWOG Cancer Research Network is basing the duration of maintenance therapy for post-transplant multiple myeloma patients on their MRD status. The University of Alabama, Birmingham is also conducting a Phase II trial, called MASTER, that is also using MRD status to determine the duration of therapy.
"The reason that MRD testing is used is because it has prognostic implications and can show how deep responses are, but we haven't done a great job of using it to guide decision making yet," Derman said. "It's logical that we didn't jump to decision making at first. You want to be able to prove that this really has significant prognostic implications first. But the area where I think the potential is greatest right now is using MRD to guide decision making."