COMy 2019 | Three key messages for MRD negativity in multiple myeloma

Nikhil Munshi

Nikhil Munshi, MD, from the Dana-Farber Cancer Institute, Boston, MA, discusses the potential of measurable residual disease (MRD) negativity, determined by deep sequencing, as a prognostic factor for multiple myeloma, and how it is being used in clinical practice. At the Controversies in Multiple Myeloma (COMy) 2019 World Congress in Paris, France, Dr Munshi explains how MRD negativity leads to increased PFS and OS compared with MRD positive patients.

Transcript (edited for clarity):

Minimal Residual Disease has now become a very important part of both myeloma research, clinical research, and it’s beginning to become important part of our patient care. A number of studies are now showing significance of attaining MRD negativity, if I crystallize the finding it suggests that deeper the response better, so if we can get MRD negativity with one cell in a million that probably gives us the best outcome. Those patients who get there have the biggest and best PFS and best overall survival.

The second message from most of the studies done so far suggests that if you get an MRD negativity, irrespective of the treatment utilized to get there, they do all same so if patient has a less treatment or more treatment if they are MRD negative their outcome would be very similar. Now this data needs to be prospectively confirmed, so this current resource forms the basis of ongoing studies to confirm it. I would not stop treatment right now in patients so if patient got MRD negativity with induction regimen can we prevent or avoid transplant – we don’t have an answer that prospectively done today. That’s an ongoing study, but the ongoing study is based on the finding that that probably is the case.

The third important message is that if we get MRD negativity, then the risk doesn’t matter. Patients who are high-risk do similarly well as patients who are standard risk if we get MRD negativity – what this tells us is that we should push to get MRD negativity in standard risk but even more so importantly in high-risk [inaudible] and so I think these are the three general messages that we can crystallize today.

So how do we utilize it in clinical practice? I think we are beginning to look at patients MRD before transplant to see if they are attaining the maximum cytoreduction – more cytoreduction, the better the results of transplant and that’s of significance. Number two, post-transplant we do MRD measurements to prognosticate how well this patient is going to do and then we can also evaluate the impact of maintenance treatment, so during the maintenance treatment 20% patients attain MRD negativity and that’s an important endpoint. So, as we give maintenance, those who are not MRD negative, we would now observe them to be becoming negative, we can predict they will have a better outcome.

The question that’s not so clear is that if after all this treat many patients are MRD positive – do I do something else do I do a second transplant? Do I do CAR T-cell? Those questions are still to be worked out so, I would not suggest changing practice just based on this, but there are a number of time points but I think MRD is becoming very important to follow and to be utilized in prognosticating and to some extent deciding how well the patient is doing. Length of maintenance treatment and consolidation are not entirely MRD driven today, but I think very soon we will be deciding how long a maintenance to be given based on MRD negativity.

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