A New Wave of Progress in The Treatment of Multiple Myeloma: Translating Evidence to Clinical Practice - Episode 4

Transplant-Eligible NDMM: Optimal Duration of Treatment

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Expert perspectives on the optimal duration of treatment in patients with transplant-eligible newly diagnosed multiple myeloma.

Ajai Chari, MD:
Another important thing to think about: name a study in which people who do better don’t do better, right? MRD [minimal residual disease] negativity in some ways is just another tool in our arsenal. Is somebody who has a VGPR [very good partial response] going to do better than a PR [partial response] or a CR [complete response]? This is our next tool.The MASTER study is a very important 1. We should take a moment to commend the study.

Does everybody need treatment forever? We need to start asking this question. Many of us feel that we’re curing maybe 10% of patients with myeloma. And if we’re treating everybody forever, we’re potentially overtreating a not-so-insignificant number. We need to start asking about discontinuation. They should be commended for the first predictive.

Until now, as Rafael mentioned, in meta-analysis after meta-analysis, it’s a prognostically very clean test. In the clinical trials, this ivory tower, where all those other tests and imaging had been done, it’s clear. But in the community we’ve all seen patients who aren’t even getting IFEs [immunofixation electrophoreses]. Maybe they get immunoglobulins and not even M [monoclonal] spike. We need to make sure we’re going to that stringency, but I want to explore more about what MASTER might be telling us because it speaks to the limitations of MRD negativity, especially at 1 time point. Even though they use 2 consecutive time points, they’re relatively close together.

Cristina Gasparetto, MD: They’re very close together.

Ajai Chari, MD: What do you think about the use of MRD? We already heard that MASTER showed high-risk patients when relapsed earlier. What do you think is going to happen with the standard risk?

Krina Patel MD: I agree with a fixed duration for our standard-risk patients. We lose patients to infections and secondary malignancies and all these other things, and we need to know who those are. Hopefully, MRD is the biomarker that proves it, because that will make it a lot easier than trying to guess clinically. But if I were a patient, and I was going to get the same amount of years, I’d also like to not be on medication.

Ajai Chari, MD: Are others are doing fixed duration firsthand?

Rafael Fonseca, MD: The perfect oncologic treatment is short and highly effective. I always think of MRD as defining the 2 boundaries: on the y-axis is the depth of the response, and on the x-axis is the duration of therapy. We can think of it as a tool that’s going to limit the duration of therapy. If MASTER pans out, it’s a major step forward. As much as we say maintenance is just a pill, that’s a big burden on patients. Even if it was just simple, oral maintenance, it can be a big burden, and the quality of life is affected. I’m excited about how MRD can change that.

Omar Nadeem, MD: I worry that these MRD-negative patients do so much better. That’s been proven over and over. If we’re de-escalating therapy on those patients, are we going to change that narrative? That’s what gives me a little pause because the standard patients are supposed to do well for a long time. Survival is well over a decade for these patients in the frontline setting. Do we alter that without knowing that first? That’s my hesitation for those patients. If you look at the duration of maintenance therapy across all these big phase 3 trials and clinical determination, it’s usually about 3 years on maintenance.

So even though the intent isn’t to see a progression, we don’t always see that. We don’t see that in clinical practice. You also saw dosing of lenalidomide was a lot lower for post-transplant patients, particularly because of their counts. So there are a lot of questions. Right now, for a standard-risk patient, MRD negative, I’d feel good about their prognosis. I still recommend maintenance until progression and would not necessarily stop it based on that.

Ajai Chari, MD: I completely agree with you. I really disagree with the fixed-duration standard risk. Keep in mind, MASTER is a single-arm study; there’s no control arm. That’s problem No. 1. Problem No. 2, we’ve had several other studies that initially looked 1 way but then follow-up is another way. FORTE was an example. At 1 year, it looked like only high-risk patient needed a transplant. With additional follow-up, everybody needed transplant. The same thing is coming out with DETERMINATION. The French study MRD negativity of transplant and nontransplant was separate. If it’s such a good test, why does it matter how you got there? Before we start, and this is the problem with using MRD at the bedside, moving from prognostic to predictive, we need prospective risk–adapted studies and not just post hoc analyses.

Transcript edited for clarity.