Future of MRD Assessment in NDMM


Paul G. Richardson, MD: Regarding MRD [minimal residual disease], Saad, if you could bring up the rear of this section and summarize where you see MRD assessment. As you’ve heard so nicely, MRD is giving us clues to what works best, and there was a very nice presentation from Paula Rodriguez-Otero, MD, PhD, abstract #62, which I thought was particularly noteworthy. Saad, what is your take on the MRD perspective?

Saad Z. Usmani, MD: Whether it’s by the next-generation flow cytometry or next-generation sequencing, MRD-negativity does provide prognostic information for newly diagnosed patients, as well as for early relapsed disease. Notably, this has been shown in several studies that were updated at ASH [the American Society of Hematology 2020 annual meeting]. I think the abstract you’re alluding to talks about the issue of having MRD-negativity in patients who may still be immunofixation-positive, and there has been this discordance in the past.

What Dr Rodriguez showed in her presentation was analysis on 2 older Spanish multiple myeloma [MM] trials with subsequent long-term follow-up, looking at MRD-negativity by flow cytometry, and looking at mass spectrometry and nature of the immunofixation and seeing if there is a difference between the survival of those patients long term. Dr Rodriguez demonstrated that there are similar PFS [progression-free survival] as well as overall survival benefits in those groups. Those immunofixation abnormalities do linger, but they get better over time as well, and that was part of the slides that she presented.

The gist of it was affirming what we already know about MRD as a prognostic tool. I think the real key for us as clinicians is going to be when we can utilize it to limit therapy in patients. Those are the questions that are being asked in clinical trials currently, including the SWOG 1803 that Amrita Krishnan, MD, FACP, is leading, comparing DARA/LEN [daratumumab, lenalidomide] versus LEN [lenalidomide] for maintenance, looking at MRD-negativity as a stopping point. I think Shaji Kumar, MD, is exploring that as an endpoint with the second randomization in the ENDURANCE trial as well.

The same is true for the CASSIOPEIA study. I think they’re looking at the DARA [daratumumab] versus no maintenance question in that study as well, with MRD as an end point and a guiding post as well.

Paul G. Richardson, MD: I agree. I think the Rodriguez abstract was so interesting, Saad, because it pointed to some of the complexity of assessing MRD, that you could have an immunofixation-positive patient who was MRD-negative. It pointed to somewhat different biology as well. I think that MRD, like all of these things, it resonates with everything we’ve discussed, is moving so quickly, and just as our therapeutics are moving so fast, so is the technology used, and the implications of MRD are evolving as well.

Transcript Edited for Clarity

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