Minimal Residual Disease (MRD) for Patients

What is Minimal Residual Disease (MRD)?
The ability to measure minimal residual disease (MRD), which is the number of multiple myeloma (MM) cells remaining after treatment, is important for prognosis. Being able to determine how many MM cells are present will ultimately allow your oncologist to determine how well a treatment is working. Performing these tests over time can show how long the effects of treatment will last. Incredibly sensitive techniques to detect MM cells have been developed, and recent data have shown that patients who achieve a deep response to therapy with no detectable MRD (MRD-negative status) have greater survival rates.

As therapies for MM continue to improve, being able to detect the “needle in a haystack” MM cells that remain after therapy is vital. Undergoing therapy often kills the vast majority of MM cells, but a few may still remain. Those remaining cells may eventually go on to grow and divide, causing a relapse. MRD testing allows for the detection of a single MM cell among a million other cells. It is hoped that the knowledge obtained from MRD measurement will inform what treatments to use, how long those treatments will remain effective, and when to begin other types of treatment. Being able to measure these few remaining cells may help researchers determine how to wipe out MM entirely. In essence, MRD measurement could become the new definition of success of MM treatment.

What is MRD Measurement?
MRD measurement is a promising, new area of research and hasn’t yet been approved by the US Food and Drug Administration (FDA) as a clinical diagnostic test. In order to gain approval and allow clinicians to use MRD measurement, its validity must be proven. The FDA will evaluate the data surrounding MRD to determine if and how MRD measurement should be used.

While MRD measurement is encouraging, there are still some questions about it. First, the methods used to measure MRD are still being refined. Two main methods exist: flow cytometry and molecular sequencing, both of which can be performed on bone marrow aspirates. Since both of these methods allow researchers to determine the number of remaining MM cells with the same level of sensitivity, either method may be used in a given laboratory. The most important task ahead is to ensure that laboratories that use either of these methods perform them the same way, so that results can be accurately compared from lab to lab. The particular method chosen is less important than the sensitivity of the results and consistency of the assays. Second, the interpretation of test results remains an area of uncertainty. Analysis and interpretation of MRD measurements can vary among labs in the US. By establishing uniform response criteria and definitions of MRD-negative status, it is hoped that MRD measurement can become further standardized.

How is the MMRF Involved?
The MMRF has been integral in bringing together the best and brightest minds to help accelerate the FDA approval of MRD measurement, by partnering with Memorial Sloan Kettering Cancer Center to organize meetings that include the FDA, the National Cancer Institute (NCI), and key members of the biotechnology and pharmaceutical industries. For more information about the latest meeting and what was discussed, please see the details on this page.

Additionally, the MMRF has collaborated with Adaptive Biotechnologies, the University of Torino, and Amgen/Onyx in a groundbreaking clinical trial, INSIDE MM-1, to perform both flow cytometry and molecular sequencing (clonoSEQ®) evaluation of MRD on hundreds of MM patients for a period of five years. For more information about this trial, see the details here.

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