What Sustained MRD Negativity Can Settle About Stopping Myeloma Maintenance

Asked how he uses minimal residual disease (MRD) status to guide treatment decisions in newly diagnosed multiple myeloma, Saad Z. Usmani, MD, MBA, FACP, FASCO, began with what the field does not have. Usmani spoke with CancerNetwork® ahead of the 44th Annual Chemotherapy Foundation Symposium (CFS).

There are no data, he said, on MRD or sustained MRD negativity followed by stopping treatment that correlate with survival outcomes as the International Myeloma Working Group (IMWG) criteria define those end points. Those trials are ongoing.

What he does act on is a specific threshold. For standard-risk patients who have achieved more than 2 years of sustained MRD negativity with no other evidence of disease on imaging, Usmani said he will have the conversation about whether continuing maintenance is worthwhile. He placed clear limits around it: the decision is case-to-case because the survival outcome data are not there, and he said the finding should be taken with a grain of salt.

Usmani pointed to the phase 3 SWOG S1803 (NCT04071457) trial, which is evaluating de-escalation of lenalidomide (Revlimid) with or without daratumumab (Darzalex) maintenance after autologous stem cell transplantation using MRD to direct treatment duration, and said it would give a better idea of which MRD-negative patients can discontinue. He expects that data within 2 years, and described the discussions until then as academic.

He was willing to name a guess and to mark where guessing stops. For standard-risk patients, it might be 2 or 3 years, he said. For high-risk patients, he said the field does not know, and that better treatments are needed for that subgroup before anyone says treatment can stop.

Usmani is a hematologist-oncologist and chief of the Myeloma Service at Memorial Sloan Kettering Cancer Center.

Transcript:

CancerNetwork: How do you use MRD to guide treatment decisions in newly diagnosed disease? What data would you need to do so more confidently?

Usmani: Right now we don’t have any MRD or sustained MRD negativity data followed by stopping treatment. [With] the way that IMWG criteria define MRD or sustained MRD negativity, we don’t have data that correlates with survival outcomes. Those clinical trials are ongoing right now.

The way that I think about using MRD negativity in the maintenance setting is once patients have achieved sustained MRD negativity for standard-risk patients beyond 2 years—so more than 2 years of sustained MRD negativity [with] standard-risk myeloma and no other evidence of disease on imaging, et cetera—I will have that conversation with my patient about whether it’s worthwhile continuing or stopping maintenance treatment. But that’s going to be on a case-to-case basis because the survival outcome data are not there yet. I think we have to just take this with a grain of salt.

We will only have that confidence when some other clinical trials, such as the SWOG S1803 clinical trial, which is looking at de-escalating maintenance, [report outcomes] and give us a better idea of which MRD-negative patients will be able to discontinue. We will keep on having these academic discussions until we get that data in the next 2 years. But my academic guess is that for standard-risk patients it might be 2 or 3 years. For high-risk patients, we just don’t know. I think we need better treatments for that subgroup of patients before we say that we can stop treatments for the high-risk ones.