Newly Diagnosed Multiple Myeloma: What’s Changing in 2025? | ASCO & EHA 

Dr. Joseph Mikhael: 

In my overview of the top 10 myeloma developments from the American Society of Clinical Oncology and the European Hematology Association, I gave an overview in three key areas in newly diagnosed multiple myeloma, in early relapse or patients who have had one to three prior lines of therapy, and indeed in late relapse, in patients who have had at least four prior lines of therapy. Today I'm going to dig deeper into that newly diagnosed category so that we can think a little bit more about what's new and even more importantly, what this means for myeloma patients when they're initially treated for their multiple myeloma. 

And please subscribe to our YouTube channel because in our next episode I'm going to dive deep into early relapse or patients who have had one to three prior lines of therapy and explore the developments that impact patients and their families in that category of multiple myeloma. 

Hi everybody. Dr. Joseph Mikhael here, Chief Medical Officer of the International Myeloma Foundation, a non-for-profit organization that is dedicated to improving the quality of life of patients with multiple myeloma while we seek prevention and a cure. 

We've come to appreciate in multiple myeloma what we do for newly diagnosed patients. Often we call it frontline therapy or their first therapy is actually really important in the long term because what we do at the very start impacts the life of the patient in the very long term. 

There was some extraordinary research presented at both ASCO and EHA in newly diagnosed multiple myeloma. And I want to dive a little bit deeper with you into three particular studies that I think are going to influence the way we think of and treat a newly diagnosed multiple myeloma. 

The first of which was the PERSEUS study. So for those of you aware of this, you may remember this because we've talked about PERSEUS before as being a very important clinical trial that compared giving four drugs to three drugs where we added daratumumab to the standard VRd or VELCADE, Revlimid and dexamethasone combination. And this actually led to its approval and use in patients who are planning to go to an autologous stem cell transplant. 

Well, the updated research was later on in this clinical trial where not only were patients given the four drugs upfront and then a transplant, and then four drugs for a brief consolidation. Now we're into the so-called maintenance phase of the study where the comparison was giving two drugs with daratumumab and Revlimid versus Revlimid alone, which is really the standard of care now. So the question is, is it helpful to keep giving daratumumab after the transplant when accompanying it with Revlimid maintenance, which is the standard of care now? 

And what was remarkable is we continue to see a big difference between the two groups favoring giving this dual maintenance therapy of daratumumab and Revlimid where the daratumumab was given for up to two years and then down to Revlimid alone. 

And I highlight this because there really is a shift in the way we're thinking. I'm not saying that absolutely every patient will be treated this way, but more and more of our patients are now having daratumumab added to Revlimid as part of their maintenance strategy. 

Secondly, let's think about what was called the MIDAS trial. And conceptually this was I think, very impactful in the way we think about multiple myeloma. In a lot of the work in the research we do at the IMF, we've been studying this concept of MRD or minimal residual disease. Basically a test that looks for tiny amounts of myeloma that may be left, even if the blood tests are normal and even if the marrow tests look quite normal. Because we know if we can eradicate myeloma down to that tiny bit and where we can't even measure it anymore, patients are likely going to do better. 

And so what the MIDAS study did is they took patients with newly diagnosed multiple myeloma, and they treated them with the four-drug combination of isatuximab or SARCLISA, plus carfilzomib, Revlimid and dexamethasone. And after giving them their initial therapy, they determined were they MRD negative or are they MRD positive, meaning is there no measurement of disease left or is there still some measurement of disease. And then those groups were randomized to two different strategies. Those who are MRD negative were randomized either to just get more Isa-KRD or get Isa-KRD plus a transplant. 

And interestingly, although the results are early, there didn't seem to be a difference between those two strategies, meaning that maybe we don't have to treat someone with a transplant if they're already MRD negative. Now, again, I don't want to make that big decision just yet, but it's showing to us that that may be one of the ways that we can use MRD to guide our treatment. 

For those patients who are MRD positive, they also randomized them to two arms to either give them a bit more Isa-KRD and a transplant or to give them two transplants, what we sometimes call tandem transplants. And similarly, those two groups didn't look very different either. So it could be that we don't have to do two transplants, although in the US we don't do as many of them right now anyway, but it may be the end of tandem transplantation. 

So I highlight this abstract because it tells us that MRD is a powerful marker, that it may help us make decisions about giving a single or a double transplant. We don't want to judge it too prematurely, but this is really changing the way we think about newly diagnosed multiple myeloma. And I suspect is going to lead to having a more individualized and personalized approach based on someone's depth of response of what further treatment they're going to have. 

Thirdly, I'd like to talk about what was called the GMMG-CONCEPT study from our friends in Germany. And this group wanted to study patients who have so-called high-risk multiple myeloma. High-risk multiple myeloma is approximately 20% of myeloma patients that we've determined with genetic testing have this categorization of high risk, meaning their disease tends to be more aggressive, tends to come back more quickly. In fact, the International Myeloma Working Group in partnership with the International Myeloma Society just defined a new definition, if you will, of high-risk multiple myeloma. And in the GMMG-CONCEPT study, they said, let's take patients who have high-risk myeloma and treat them a little bit more aggressively than we typically would, giving them the four drug combination of isatuximab, carfilzomib, Revlimid, and dexamethasone, doing a transplant, and then continuing that Isa-KRD, as we call it, eventually dropping off the dexamethasone, but at least continuing the Isa-K&R indefinitely. 

And it was remarkable because historically, unfortunately, high-risk patients tend to relapse very quickly. But here they had very good outcomes in the long term in patients treated a bit more aggressively. And I think what it's teaching us is two things. One, that we do need to treat more aggressively patients with high-risk disease. And two, they discovered those patients that did really well were the ones who achieved MRD negativity. And so it really is an important goal in likely all patients, but in particular in high-risk patients, that we seek that MRD negativity or to eradicate the disease as much as possible, even a little bit of disease left at the end. Sometimes I say, Rambo is the last soldier to be killed. We leave that little bit of disease left, it can grow back quite aggressively. And so it's important to eradicate that. 

I find it fascinating that these three studies that I've mentioned, the PERSEUS study, the MIDAS study, and now the GMMG-CONCEPT study all have very close ties to MRD negativity. And we all believe in the myeloma community that MRD is going to be a very powerful tool as we care for our patients. 

So in summary, we're using quadruplets upfront in literally all patients going to stem cell transplant. We're likely going to be using more dual maintenance therapy as we go forward. We're likely going to be using MRD to help guide us as to who may or may not need an autologous stem cell transplant. And lastly, that high-risk patients need that continuous, more aggressive therapy to control their disease in the long term. 

These are really exciting developments in multiple myeloma, and I trust this will be helpful to you and your family as you are treated for multiple myeloma, because as you understand more and as you participate more in your care, your outcomes will be better. 

So with all these great clinical trials that we've been describing, you might say to me, "Dr. Joe, how can I participate in a clinical trial?" Well, we've made the process easy for you to search and find a clinical trial that's relevant to you. In partnership with SparkCures, we've created on our website a search engine that can find a clinical trial for you. So come to our website, myeloma.org/sparkcures, and begin your searching today. 

Thanks so much for watching. If you found this video helpful, please subscribe to the IMF's YouTube channel so you'll never miss updates in myeloma research, in education, and in support. In fact, if you want to learn more, here are a couple of videos you might be interested in.