ASH 2021 | Where does MRD belong as a tool in myeloma?
As part of the ‘Challenges in Multiple Myeloma Treatment’ session, Noopur Raje, MD, Massachusetts General Hospital, Boston, MA, discussed the unknowns on measurable residual disease (MRD) in multiple myeloma. Technological advancements, together with a growing understanding of disease biology, have enabled substantial progress in this area. MRD can be measured highly sensitively, and accumulated evidence has clearly demonstrated that it acts as a robust prognostic marker, with patients who achieve MRD-negativity performing better across all subgroups. However, controversy remains regarding where to use MRD and how it can help to tailor therapy in an individual. More and more trials are incorporating MRD, with some ongoing trials looking at its use as a tool to guide treatment escalation or de-escalation. Dr Raje shares her thoughts on where MRD is helpful right now and how this is likely to expand in the coming years. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Transcript (edited for clarity)
The MRD data that I will be talking about is more talking about controversies and challenges in the field of myeloma. And I will be discussing this at an educational session at ASH. So MRD is minimal residual disease. I’ll talk about how we look for MRD, what are the techniques we use, whether it’s next generation flow cytometry, or next generation sequencing. It really doesn’t matter, but the level of sensitivity that we can detect minimal residual disease today in myeloma is one in a million cells, which is quite remarkable...
The MRD data that I will be talking about is more talking about controversies and challenges in the field of myeloma. And I will be discussing this at an educational session at ASH. So MRD is minimal residual disease. I’ll talk about how we look for MRD, what are the techniques we use, whether it’s next generation flow cytometry, or next generation sequencing. It really doesn’t matter, but the level of sensitivity that we can detect minimal residual disease today in myeloma is one in a million cells, which is quite remarkable. I think more and more of the clinical trials that we are doing, we are incorporating MRD into the clinical trial testing.
And so far we’ve been overwhelmingly, been able to demonstrate that if you are MRD negative, you do better than patients who are MRD positive. So based on that data and based on the fact that we have treatment algorithms now, which really give very high response rates, wherein we are seeing 80 and 90% of our patients responding. Having more sensitive tools to look at response is the way to go in myeloma, and MRD negativity really is the new complete response that we used to use many years back.
So as we’ve gone forward with all of the different treatment approaches, incorporating novel response criteria is really very important. And as far as prognosis is concerned, it is very clear that MRD negative disease does much better, not just with progression-free survival, but overall survival as well. And it doesn’t matter in which subtype of patients, you look at standard risk, high risk, genetically high risk, newly diagnosed, relapse. So as a prognostic factor, I think the debate does not exist anymore. It is a very robust prognostic marker, and we are incorporating that in clinical trials. I think the controversy lies in where do you use MRD? And can you tailor therapy with MRD? So can you use MRD as a tool to decide on what a patient should receive in terms of therapies? I don’t think we have the answers to that just as yet.
And I think that’s where there’s ongoing work and that’s where the debate is. So should I be using MRD in my standard practice when it doesn’t dictate what I do to treatment? And part of the reason for that is, MRD can happen over time and MRD can deepen over time. And therefore, just looking at one time point with MRD should not give you the license to change treatment just as yet. There are ongoing trials, which I will be discussing looking at MRD as a tool to sort of either escalate or de-escalate treatment and even consider stopping treatment.
So, these are things which are in the context of a clinical trial. I do think one of the things that we will be discussing is, so where is it useful right now? And I think most of us would agree that in high-risk disease, it’s really important to get to that MRD negative state and try and maintain that MRD negative state. So in practice, that’s the one specific area that I do look at MRD testing, if not in other specific situations. And as part of clinical trials, I think we need to incorporate it, and for the future, this is going to be our tool in trying to sort of dictate how long you treat, how much you treat, whether you escalate or de-escalate treat. So it’s going to be a really important tool going forward in the management of our myeloma patients.
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