Treatment Strategies for Patients With Transplant-Ineligible NDMM

Expert perspectives on selection of induction therapy for patients with transplant-ineligible newly diagnosed multiple myeloma.


Melissa Alsina, MD: We talk about the importance of maintenance therapy, continuous therapy in newly diagnosed patients who are transplant ineligible. What about this population, should they stay in therapy? Should everyone be on maintenance?

Ken Shain, MD: That’s a great question, I think we’ve had data for over a decade saying that for our disease state, for myeloma, continued therapy is the best option for our patients, not just these papers we’re talking about now. But continued therapy, what does that mean? I think the MAIA study highlights the fact of being on at least 2 of those drugs. I try to get rid of dexamethasone, as fast as I can, once I get to a response, because most patients, period, don’t like dex [dexamethasone] for very long. But being on dara [daratumumab] and len [lenalidomide] for a long time provides you with a really nice outcome. The SWOG S0777 trial, I think is a little handicapped because of the design, the way bortezomib was given, 1 short time, both dose-dense, IV [intravenous] until later, minimized its ability to see what it can do long term. So even for those patients, I like to have the proteasome inhibitor as maintenance therapy as well. I think continued therapy is the right answer. Again, I stop for the same 3 reasons we talked about before: progression, toxicity, and financial toxicity. But I think we have an exorbitant amount of data in our disease state that continuing therapy is the best. Lastly, I’d love to figure out who are those patients we can stop, because life is a lot easier if you’re not taking [lenalidomide], and you’re not seeing us, etc. But we don’t have that information yet.

Melissa Alsina, MD: Yes, and to emphasize that when we treat these patients, particularly older patients, they don’t necessarily need the full doses of all these drugs. Frequently we see these patients, and they’re sick from the treatments that were given, rather than the disease. So it’s very important to back off, as you mentioned, Ken, from the dexamethasone, it has a lot of adverse effects, especially for this patient population. Back off from the dexamethasone as soon as you can. And reduce the doses of the IMiD [immunomodulatory drug]. The other thing, even if you decide you’re going to start, for example, a proteasome inhibitor in a patient because [they are] high risk, you don’t necessarily have to keep that proteasome inhibitor indefinitely. Dose adjustments I think are critical, more so in this patient population.

Brandon Blue, MD: Yes, and I think something you can also consider, the same way we do these kinds of adjustments for patients when we consider the upfront therapy, you can also consider the depth of response. If you have a patient that you have on all these multiple drugs, and the patient is responding well, the treatment is going exactly the way you anticipate, maybe sometimes you can back off a bit. Maybe you can even overtreat this patient; maybe the patient doesn’t need all those drugs to still get the same effect. Those are the things to think about. Or you say, maybe I’m undertreating them, maybe the patient has gotten a couple of cycles and has only gotten a 50% reduction. You say, “I could probably do better.” So don’t be afraid sometimes to say, well, this patient might not be transplant eligible, but maybe they still might need some more therapy.

I think if you are considering this patient, and you haven’t given the patient daratumumab, maybe it’s time to add it. Or you say well, maybe I gave them this DRd [daratumumab, lenalidomide, dexamethasone] up front, but they just aren’t responding how you would have thought. Maybe consider a proteasome inhibitor. I think we have these buckets sometimes that in our brain can be so rigid, give them this or that. But I think sometimes the patient’s story can be very fluid, and you can make a decision based on the responses that the patient’s biology of their disease is telling you, of how they’re going to respond.

Rachid Baz, MD: Yes, absolutely. I think the trials are designed in a way that you pick up front 2 regimens that you pit against each other, but in reality, in life, it doesn’t have to be this way. You can accommodate based on your patient’s experience, their response, and tolerability, as Brandon mentioned. Melissa mentioned that there might be a subset of patients who would be considered transplant ineligible for whom maybe dara [daratumumab] and RVd [lenalidomide, bortezomib, dexamethasone]-lite could be considered for example, too. I think this allows us to have more flexibility in terms of treating patients and personalizing their care.

Ken Shain, MD: I think the goals of your therapy may be a little different. Like Brandon definitely hinted at it, Rachid said the same thing. When we talk about transplant-ineligible patients vs transplant-eligible, eligible when you think of MRD [minimal residual disease] negativity as a goal. I don’t think that changes, but I think our willingness to not be there, and have a little less response and control of disease, might be a little better too depending on that patient, right? Balancing the toxicities of frailty, etc. Just things to also go into what I think Brandon was suggesting.

Melissa Alsina, MD: Yes, but I think now with the data from the MAIA study, for example, a high proportion of these patients actually get to MRD negativity. It takes time, that’s another thing, to get to MRD negativity. It doesn’t happen like a response, that happens after a month, you see a response. It’s going to take time; the median time within MAIA was about a year. I think everything is changing. I think in the past we were trying to just give palliative therapy to these patients, and we would be OK with a PR [partial response]. But I think right now these patients can respond much better, and it definitely has an important impact on their quality of life, and obviously, their survival.

Transcript edited for clarity.

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