What are the Controversies Surrounding MRD in Blood Cancers?

Alan Skarbnik, MD, of Novant Health, and Manni Mohyuddin, MBBS, of the University of Utah, join Chadi Nabhan, MD, MBA, FACP, on “The HemOnc Pulse” to discuss the concept of measurable residual disease (MRD) in hematologic malignancies and highlight the polarized views surrounding MRD.

Dr. Nabhan described MRD as the ability to detect a disease that is unable to be detected conventionally. “Isn’t that a good thing?” he asked.

“The technology of MRD is a big step forward for our field,” Dr. Mohyuddin said. He explained that response assessments in multiple myeloma are based on indirect markers of the cancer—and proteins made by the cancer—as opposed to directly measuring the cancer itself.

“We can measure small amounts of cancer in the bone marrow now, and we’re directly measuring those cancer cells with our assays,” he said. “That is a step forward.”

According to Dr. Mohyuddin, the MRD controversy lies in how to act upon these data and whether clinicians are overtreating or undertreating patients based on the data. “It raises a whole set of questions,” he said. “The technology has gone forward in leaps and bounds, and now the trials on how to act based upon the technology are following. Until we see results from those trials, I am exercising some caution.”

Dr. Skarbnik noted that which MRD test clinicians use and how that test is interpreted is also controversial. “Are we using it to monitor disease? Are we using it to monitor treatment success? Are we using it to decide when treatment can be stopped, or are we using it to decide when treatment should be started? Those are the questions across diseases that we don’t have firm answers on yet,” he said.

Dr. Mohyuddin also noted that MRD negativity is not a cure for cancer. “MRD negativity can often be fleeting,” he emphasized.

Next, they discussed the difference between prognostic markers and surrogate markers. “MRD is well established as a prognostic marker, meaning that those who achieve MRD negativity with therapy do better than those who don’t,” Dr. Mohyuddin explained. “When we’re talking about surrogacy, the question we’re trying to answer is, ‘Does giving additional therapy to try to achieve MRD negativity lead to differences in overall survival?’”

Finally, the trio considered harmonizing the MRD threshold. “Why can’t you people agree on a threshold beyond which MRD is positive or negative?” Dr. Nabhan asked.

“We are trying to get consensus in the field,” Dr. Mohyuddin said. “This is a field that is evolving very rapidly, and we are changing things.”

Related: Is MRD Negativity the New Benchmark in ALL Treatment Strategies?