New Trial Data Informing Optimal Care of Frail Patients with NDMM

EP: 1.Patient Case Introduction: A 65-year-old Female Diagnosed with Transplant-eligible NDMM

EP: 2.An Introduction to Treatment Strategies for Patients with NDMM

EP: 3.Key Trial Data Guiding Treatment Decisions for Patients with NDMM

EP: 4.NDMM Risk-Stratification and Other Factors Informing Treatment Selection

EP: 5.Patient Case Introduction: A 76-year-old Female Diagnosed with Transplant-ineligible NDMM

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EP: 6.New Trial Data Informing Optimal Care of Frail Patients with NDMM

EP: 7.Clinical Insights Concerning the Management of Patients with NDMM

EP: 8.Patient Case Introduction: 66-year-old Male Diagnosed with R/R MM

EP: 9.Determining Who Should Get Quadruplet Vs Triplet Therapy in Multiple Myeloma

Dr. Sagar Lonial: So, Dr. Nooka, can you give us a little bit more commentary around MAIA. How we got there and what we know with even longer follow up?

Dr. Ajay Nooka: Absolutely. So, I'll give a little background of how lenalidomide dexamethasone became the standard of care in the United States. So, the first trial is one of the largest trials in transplant ineligible patients or frail patients, where they tested a finite duration of lenalidomide dexamethasone versus lenalidomide dexamethasone until progression versus chemotherapy based approach in combination with thalidomide. So, the winner here is lenalidomide and dexamethasone given until progression in the newly diagnosed myeloma. We always wanted to find what can we do more for the patients? So that's where the MAIA trial comes in, where lenalidomide dexamethasone of the standard of care arm. What does addition of daratumumab offer for these elderly patient population? So, the control arm, I always want to look at the control arm first before I look at what the addition is. In the MAIA trial, the control arm showed 30 months, which is much longer than what I expected, or I'm happy with that regimen. But what did data add? So, the first ever time the trial reported in 2019 or 2020, at a median follow up of 30 months, you were able to see the control arm had a PFS of 30 months and a hazard ratio of 0.56, that is a 45% reduction in the risk of progression. And there was overall survival benefit as well. There was a 35% reduction in the risk of death. So now last year, towards the end of last year, we had the follow up after 60 months, close to 65 month of follow up on the regimen. What we are able to see is the median PFS for the elderly patient, your 76 year old patient, you're able to see the median PFS is beyond that 60 month mark. We've never seen that in the transplant ineligible frail patients before. So that became the standard of care and that's how I would really love to use that regimen because it is number one, very tolerable, convenient. And after the first six months, patients are receiving daratumumab once a month and then lidomide continuously. So, what it has resulted was the risk of death has decreased by 35%. And at that follow up of six years, you're able to see two thirds of the patients alive on this regimen compared to a half of the patients on the RDM. So, this is a great win. Unless proven otherwise, I would really want to use this as the standard of care regimen at this point of time, which yields better depths of responses including negative scene in frail patients in a third of them.

Dr. Sagar Lonial: So, I think we're going to get to frail patients in just a moment. I know that Dr. Joseph is going to give us that sort of spin. But I do think it is interesting to look at the MAIA trial because not only does it have the long follow up and really the PFS data that we've never seen. But we do know also that the percentage of high risk patients actually diminishes as the patients get older. And so, I think that that's an important thing to keep track of, is that when you get, and there was almost 20%, 20, 25% of patients that were over the age of 75 in that trial. You may speak to that a little bit as well. The incidence of the high risk genetics actually drops pretty markedly. So that to me is an interesting dichotomy, that while it is an easily effective and very easy to deliver, you don't have to think about risk as much in the truly older patient population. You tell us about the frailty patient.

Dr. Nisha Joseph: So again, recognizing that a large chunk of the patients were over age of 75 and that we're using this regimen in patients that we consider frail. There was a subgroup analysis looking specifically at patients who were frail versus non frail. And so, what they found in terms of PFS using different scores was that patients even who were frail did better on the triplet than patients who were not frail with the doublet. So, I think when I think about this regimen, dara-len-dex, dara is not the drug I think about causing a lot of toxicity even in an older frail patient. And like Ajay said, the convenience factor is there once we get through those initial six months, these are monthly visits. The dex, I also taper off in the first year. So, I think it's a really tolerable regimen even for patients who we might consider frail by whatever score that you might choose to use.

Dr. Sagar Lonial: And again, I think another thing to build on there is with the truly frail patient, which may not be the 65 or 67 year old that they enrolled on MAIA, you may only get one shot to treat them. And so, if you don't get it right that first time, and I think Rafael's got some retrospective data that speaks to that as well. If you don't get it right the first time, you may not get a second shot. Whereas if you can make them better with an easy regimen, you may get a second shot and that's certainly worth knowing a little bit as well. So, Dr. Kauffman, we've been talking a lot about what I think all of us would agree is a standard in this space, which is a CD 38 dara plus len-dex, there is some data on MagnetisMM-6 that was presented. Give us some information on that.

Dr. Jonathan L. Kauffman: Well, so this is a trial in progress and asking the question, can we bring the ABECMA targeted therapy into the upfront non transplant eligible patient population. There's an initial study of the three drug combination to identify the optimal dose of the three medications. And then it's going to be the randomized study of the BCMA bispecific daratumumab lenalidomide versus the, again, the MAIA protocol. So very interesting in asking the question. Because on some levels, we feel very good. The median progression-free survival is 60 months. That's great. On the other hand, the median progression-free survival is only 60 months. And that means by definition, we can do better. And this is, these are really effective therapies bringing in the BCMA bispecifics, and can we add them to our initial therapy to make outcomes better?

Dr. Sagar Lonial: I think it's nice to have those sort of forward looking studies. There are many of them looking at BCMA directed therapy with different modalities in an older frailer patient population as well.