Selecting The Appropriate Treatment in Transplant-Eligible Newly Diagnosed MM

A brief discussion how to select the appropriate treatment strategy in transplant-eligible newly diagnosed myeloma and whether there is a role for minimal residual disease in assessing response and treatment duration.

Sagar Lonial, MD:
The big topic is MRD [minimal residual disease]-directed therapy. What we heard very clearly from the FDA [Food and Drug Administration] at the IMS [International Myeloma Society] FDA workshop is that our data is all over the map. Some people look at cycle 4, some people look at cycle 6, some people look at 1 year, some use 10-5, some use 10-6. I think one of the things certainly that I’ve been advocating for, and [what] I’m curious how you all feel about, is rigor in the time points. Let’s look at 6 months and 12 months and who’s MRD negative and at what depth, and then, is that sustained? To go way back, a paper was published a long time ago about sustained CR [complete response]. The patients that got CR and then lost it did worse. If you only look at a single time point, you don’t have the ability to map out that biology.

Samuel M. Rubinstein, MD: I totally agree. I think MRD is most useful as a biomarker in a sustained capacity as opposed to a single time point. Sandy brought up the excellent observation, and several studies have shown this. Patients with high-risk myeloma are not necessarily less likely to achieve very deep remissions; they’re just not always sustainable. To your point, if we’re going to be moving toward using MRD to drive advances in therapy and regulatory decisions, we need to be more standardized to the community.

Sandy Wong, MD: We also need to be standardized about how we define MRD, because there’s, obviously, your NGS [next-generation sequencing], there’s your NGF [next-generation flow], and then some people add in the imaging on top of that, then the type of imaging. On the further end in terms of technologies are in development is using immuno-mass spectrometry. We really had to come together as a community to figure out what tests we are going to order for MRD testing and do them at defined points as opposed to being all over the place.

Sagar Lonial, MD: I’m curious how you all do this. At our center, we do MRD testing at 1 year and we do PET [positron emission tomography] CTs at 1 year as well. We have found some discordance there. I think it is important, but is that something everybody’s doing?

Timothy Schmidt, MD: It’s not, really. We are typically checking MRD at day 90 [or] day 100 post-transplant restaging. Then our institution hasn’t been doing bone marrow biopsies on everybody on a recurring basis necessarily because it’s very rarely impacted our management decisions. If we come together as a community and agree that based upon these specific time points and as that data reads out, we can have more informed discussions with our patients and make more informed decisions about what to do, then I definitely would be open to starting to do that again at those kind of routine intervals.

Caitlin Costello, MD: For the sake of debate, because all of us have drunk the Kool-Aid of MRD, does everyone need to be MRD negative? We do see patients who regress back to some kind of a smoldering phenotype or an MGUS [monoclonal gammopathy of undetermined significance]-like state. Are we overtreating those patients to achieve a goal that maybe they don’t necessarily need to meet? That’s another unmet question here. Yes, we need to agree on are we using NGF, are we using NGS? What are the time points? Are we doing it? How deep do we need to do it? We need to also answer the question, does everybody need to get to that level?

Sagar Lonial, MD: Certainly, in our experience, we’re not changing if we see that they’re MRD positive. If they’re PET positive, we might. That’s probably a little bit of a different situation, but certainly, I’m with you. We really use it to track outcomes and then go back and say, did these people actually do OK even though they didn’t achieve MRD negativity?

Sandy Wong, MD: On top of that, at our institution, for day 90, we always do bone marrow biopsies. We always send MRD. We use next-generation sequencing, but when it comes to imaging, we do not routinely do it. A lot of it has to do with insurance because they’re going to [ask us to] show [them,] the data that tells [them] that this is actually useful. It’s scattered, it’s not consistent. That really speaks to the point of [that] we really need studies to show that, as opposed to just us doing it in clinical practice.

Transcript edited for clarity.

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