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COMy 2022 | The value of MRD as a prognostic tool in myeloma

In this video, Meral Beksac, MD, PhD, Ankara University, Ankara, Turkey, shares some insights into the role of measurable residual disease (MRD) negativity and its role in treatment decision making in myeloma. Prof. Beksac first highlights the importance of MRD as a topic within myeloma, and further discusses how techniques used to measure MRD have improved over the years. Following this, Prof. Beksac discusses a debate held at COMy 2022 in which she gave her opinion on whether MRD negativity should be used to change treatment approaches. To conclude, Prof. Beksac mentions the benefits of using MRD negativity as a prognostic factor, and how MRD data can be applied to high-risk patients. This interview took place at the 8th World Congress on Controversies in Multiple Myeloma (COMy) 2022, held in Paris, France.

Transcript (edited for clarity)

Well, certainly, measurable residual disease is a very important topic. It’s been going on for a long time. And the issue with measurable residual disease is the techniques have improved tremendously through the years. And we have now reached and talking about ten or a minus seven, and earlier we were confident with minus five, and, of course, not only the techniques have improved, but also the origin of the cells that we are searching for has changed...

Well, certainly, measurable residual disease is a very important topic. It’s been going on for a long time. And the issue with measurable residual disease is the techniques have improved tremendously through the years. And we have now reached and talking about ten or a minus seven, and earlier we were confident with minus five, and, of course, not only the techniques have improved, but also the origin of the cells that we are searching for has changed. Earlier, bone marrow was the only location to look at for MRD. And later imaging was introduced and it was published that PET imaging and marrow MRD are complementary and both negativity are important, which shows the lowest level of disease burden after treatment.

And now we are talking about even a further technique, which is looking with mass cytometry with either liquid chromatography to measure the monoclonal proteins at a very sensitive level in blood. So, this overcomes the heterogeneity of the disease distribution within the body. And looking into the blood and measuring the M-protein in a very high sensitivity technique, allows another complementary method with the bone marrow MRD. So, this has also been published recently.

And, based on these developments, the clinical data so far, I think that on my composition in the debate, I will be talking and advocating that the data in the clinical trials we have so far is based on the traditional, old-fashioned data. And, of course, I cannot argue against the value of MRD as a very significantly, highly important prognostic factor. Maybe it’s even more important than the risk assessment at diagnosis. And, certainly, it’s an independent factor. However, for today’s routine daily practice, we cannot recommend centers or physicians or patients to change and adapt their treatment based on the MRD achieved.

There are maybe two topics that deserves attention. And one is the technique that I am talking about. Not all centers have these high-sensitive level of detection methods. And, secondly, the disease can be very high-risk. And although you achieve MRD negativity, you may have a progression of disease if you stop treatment. So, for de-escalating and stopping purposes, MRD assessment cannot be useful for all patients, mainly for high-risk patients. But, for those very limited number of very good prognostic patients who are very sensitive to regimens, induction, and transplant, some of those patients may really benefit. And if they achieve MRD negativity, even with the current available techniques, they might be the candidates who may benefit from stopping maintenance. Today, we have recent data from maintenance studies and it shows that, on maintenance, the majority of patients convert from MRD positivity to negativity within the first year. So, continuing a therapy beyond a year where they no longer have a deepening of response, may be questionable. But, it’s still early.

And, finally, I would like to mention that today there are more than 10 clinical trials based on MRD adapted regimens. And most of these trials are on de-escalation and stopping purposes. We do not have data to support the role of intensifying or changing therapy based on continuous MRD positivity. So, there is still open space for this missing amount of data.

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