Educated Patient® Multiple Myeloma Summit Role of Sustained MRD Negativity Presentation: November 13, 2022

Measuring minimal residual disease, or MRD, allows physicians to better understand if treatment is working, which highlights the need for patients to be sure they are asking to be tested, according to an expert.

Dr. Benjamin T. Diamond, an assistant professor at the Sylvester Comprehensive Cancer Center at the University of Miami, further explained what MRD negativity is and how it is tested at the CURE® Educated Patient® Multiple Myeloma Summit.

“It’s not necessarily rocket science that if (a patient) has a deeper response, the less myeloma is left over, the better they are going to do over the long term,” he said in an interview with CURE®. “Multiple studies have recapitulated that the deeper the response, and with negative MRD, patients are doing better following induction therapy and on maintenance. And then obviously, if that response with negative MRD is sustained for a long period of time, then patients do exceptionally well over the long term. And so, our interest then is trying to achieve MRD negativity with strong therapies for as many people as possible.”

Diamond continued and said that everyone’s disease biology is different, and there is still work being done to personalize therapy to achieve MRD negativity. But, currently the best way to achieve it is to use the strongest and most potent therapies in the frontline setting, this includes quadruplet therapies (a four-drug regimen).

However, it is not the end-all-be-all in this patient population, Diamond said, explaining that at the general level, MRD negativity means that therapy has been working and the disease is being “knocked down.” It is not used to make a treatment decision, he added, but more so as a checklist to monitor how a patient is responding to treatment.

“MRD negativity is a prognostic measure,” he explained. “It doesn’t fully encapsulate everyone’s disease biology. And it’s not always assured that achieving it or not achieving it is going to predicate what’s going to happen in the future.”

Measuring MRD allows physicians to look deeper than traditional markers of response, such as complete response or a strict complete response. This required to have less than 5% of plasma cells in the bone marrow and it wasn’t known if those cells were malignant or not. But MRD testing allows them to look more precisely at those cells to determine how many malignant cells are left over after treatment.

MRD is measured through two different tests, the first being next generation sequencing. During this, the monoclonal protein immunoglobulin heavy chain – which every patient with myeloma has – is barcoded at the start of treatment and followed over time to watch for changes. If a patient already has a bone marrow biopsy on file, that can be sent out and used to measure MRD.

“As long as patients are aware of it and can tell their provider about it, it’s something they can do pretty much do wherever,” he noted.

The second type of test is a flow cytometry test, which is when sensitive cells of a column are taken and counted to determine which are myeloma cells and which are not. However, the challenge with this is it can only be done in an academic setting.

Further, these tests are not always available to patients — whether it be due to technology reasons or a lack of knowledge from providers. This highlights the need for patients to better understand and be educated on this topic so they can advocate for the best care for themselves.

“The more (patients) know about it, the more they can help to advocate to try and get it for themselves,” Diamond concluded. “The more they know about MRD, the more they can advocate for stronger treatments in the frontline because we all want to achieve this. … And secondly, it also can give them the peace of mind to know that their therapy is working. If they achieve that MRD negativity, they can rest assured that, in the majority of cases, they're going to do very well over the long term.”

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