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Clinician Attitudes are Shifting on MRD-guided Decision Making in Multiple Myeloma

Allison Jacob, Senior Medical Director, Minimal Residual Disease

This September marks four years since the 2018 Food and Drug Administration clearance for clonoSEQ to detect and monitor minimal residual disease (MRD) in bone marrow from patients with acute lymphoblastic leukemia (ALL) and multiple myeloma (MM). In the years following, researchers have explored the value of using MRD status to guide treatment in blood cancers – and the mounting evidence has been substantial in making the case for clinical actionability of MRD in MM. As a result, clinician attitudes are evolving, particularly following the dissemination of MRD-guided study designs such as the MASTER trial.

This evolution is captured by a 2021 survey of 89 oncologists, published in Blood Cancer Journal last month, aimed at understanding clinicians’ general attitudes toward the use of MRD and how MRD status might impact decision-making in common clinical scenarios. Responses were received from oncologists who treat multiple myeloma patients in academic and non-academic settings, with the median clinical experience being 10 years. Of these clinicians, 57 (64%) indicated they assess MRD as part of myeloma patient care.

An additional survey of a subset (68) of the respondents revealed a significant increase (37% to 60%) in clinicians reporting use of minimal residual disease (MRD) status as a guide for making treatment decisions in MM compared with a prior survey in 2018. Other findings demonstrated that:

  • 78% would change a clinical decision based on presence of high-risk disease.
  • 60% would change a decision based on an MRD result.
  • 54% of respondents would use a combination of both MRD status and disease risk to make decisions either to intensify therapy in MRD positive patients, or to de-escalate or stop therapy in MRD negative patients.
  • Notably, nearly 40% of respondents said they would discontinue treatment if a patient was sustained MRD-negative and standard risk.

Independent of whether MRD was being used in clinical practice, 56% of all responding clinicians indicated concern that there was not enough data to support decision making. Despite the progress being made, there is still a desire to see more data to support the use of MRD.

Closing the Gap

Multiple factors may be driving the evolution of views reflected in the updated survey: the availability of highly sensitive technologies such as clonoSEQ, real world and study data reporting the impact of MRD-guided treatment, and an increase in the number of trial strategies using MRD to guide therapy.

Adaptive is committed to improving the lives of people living with cancer. To do that, we are actively partnering with researchers to deepen understanding of the impact of MRD use for clinicians. Some key studies to watch:

  • MRD2STOP, led by Dr. Derman, and SWOG S1803 are evaluating whether MRD-negative patients who are on maintenance therapy can safely and effectively discontinue treatment.
  • MASTER, led by Dr. Luciano Costa of the University of Alabama, Birmingham, in which patients with persistent MRD negativity after quadruplet induction and consolidation therapy (including transplantation) proceeded to discontinue all therapy, even maintenance lenalidomide.
  • REMNANT, led by Fredrik Schjesvold, assessing use of MRD positivity to initiate treatment post-transplant.

MRD testing has strong prognostic value and gives us more information than ever on depth of response. MRD-guided decision-making has the potential both to save patients from unnecessary exposure to toxic, expensive therapies, as well as guide intervention prior to clinical relapse. Building on existing data to bring MRD into routine care for all myeloma patients is the next frontier.

clonoSEQ® is available as an FDA-cleared in vitro diagnostic (IVD) test service provided by Adaptive Biotechnologies to detect minimal residual disease (MRD) in bone marrow from patients with multiple myeloma or B-cell acute lymphoblastic leukemia (B-ALL) and blood or bone marrow from patients with chronic lymphocytic leukemia (CLL). clonoSEQ is also available for use in other lymphoid cancers and specimen types as a CLIA-validated laboratory developed test (LDT). For important information about the FDA-cleared uses of clonoSEQ including test limitations, please visit 

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