Dr. Joseph Mikhael:
Last month, the American Society of Clinical Oncology, also known as ASCO, and the European Hematology Association, known as EHA, held their annual conferences. Today I'm going to break down for you Dr. Joe's top 10 developments in that research presented at ASCO and EHA. They'll be grouped together in three categories: frontline therapy, how we initially treat myeloma; early relapse, how we treat patients who have had one to three prior lines of therapy; and then late relapse, how we treat patients who have had at least four prior lines of therapy.
Please subscribe to the YouTube channel and follow us as we learn more about how this impactful research is going to change the way we treat multiple myeloma. All right, let's dig into these top 10 that I've shared with you. I've put them in three categories. Category number one is frontline therapy, and here I would talk about three specific abstracts.
Abstract number one was called the PERSEUS trial. This is the trial that really changed the way we treat myeloma by going from three-drug combinations to four-drug combinations in patients who are going to autologous stem cell transplant. Specifically, the four drugs were daratumumab, bortezomib, lenalidomide, and dexamethasone together. The update we had from ASCO and EHA this year showed to us that after giving those four drugs and a transplant, here, two drugs were given with daratumumab and lenalidomide compared to just lenalidomide alone, and it was remarkable. Those patients had extraordinary outcomes, where over half of them went into MRD negativity, or minimal residual disease negativity, for over two years. I think this is going to mean that we're going to use more dual maintenance therapy in multiple myeloma.
Abstract number two on the subject of MRD negativity was the MIDAS trial, and the MIDAS trial used this strategy after giving patients four drugs with isatuximab, carfilzomib, lenalidomide, and dexamethasone and determined if they are MRD negative to give them a certain strategy, or if they're MRD positive to give them a more intense strategy. It's a little bit early to make final conclusions, but we're already seeing from this strategy that patients who achieve MRD negativity may not absolutely need an autologous stem cell transplant, and those patients who are MRD positive may not need as intense therapy with two transplants. And we need to wait a little bit longer to see the results of this, but this could be very impactful in the way we treat myeloma.
Thirdly, we saw what was called the GMMG-CONCEPT study, which focused on high-risk multiple myeloma. I'll remind you that about 20% of patients up front have high-risk myeloma, where traditionally it's been really difficult to treat these patients. They gave a more intense regimen by giving a four-drug combination, then a transplant, but then continuing the four drugs, eventually dropping the dexamethasone, so really three drugs, and we saw outcomes of these patients much better than historically we've seen with high-risk myeloma. So this gives us more hope in treating that challenging form of the disease.
Well, the second category that we're going to think about today is early relapse. I'll start with the drug belantamab, a drug that was removed from the market but almost definitely will make its way back in the near future. And we had two important studies, the DREAMM-7 and the DREAMM-8 study, where belantamab was given in a triplet combination and really had extraordinary outcomes, including one of the studies that had three years of remission on average in these patients treated with this triplet. We're almost definitely going to see belantamab come back soon, and it's nice to know that we're going to have different options in the way we use it.
Secondly, there was an interesting way of delivering the drug isatuximab. Historically, we've given it intravenously, but now they have a new form of subcutaneous or in-the-skin delivery, something called OBI, on-body injector, and it's a little device that sticks to the skin and there's a tiny needle inside that pushes the drug into the skin over about 12 to 13 minutes. And patients really appreciated the way that this was given to them, and it might even mean someday that we could give it to patients at home.
Lastly in the early relapse category, we saw a series of abstracts bringing bispecific antibodies, drugs that we typically use now in late relapse, into the early relapse setting. And I was very encouraged by this because I think this is going to give us even more options for patients in the near future for their early relapse and how we can treat them with these very effective therapies.
Lastly, the third category was late relapse, patients who have had at least four prior lines of therapy. Lots of amazing research here, but I'll give you four abstracts and I'll start with the one that is arguably the most impactful of all the abstracts presented at these two meetings. It was the long-term follow-up of the CARTITUDE-1 study. This was where we gave cilta-cel, or Carvykti, as a one-time CAR T-cell infusion. And what was remarkable about this was that one-third of patients, 33% of them, five years after that infusion are still completely disease-free. It even has us starting to think about the concept of how do we define cure in myeloma. I'm not saying these patients are cured, but here they are receiving no therapy, disease-free five years later. Very exciting research.
Similarly, number two was the trispecific study. So we use bispecific antibodies now where one arm of the drug hooks onto myeloma, the other arm hooks on to a T-cell. Now we actually have trispecifics. I don't have three arms here, but the two arms grab onto the myeloma cell and the third arm grabs onto the T-cell. This allows it to be more precise, and what was remarkable was not only did these trispecifics have very strong response rates, they also seemed to have less of the side effects than when we were giving them as bispecifics or as two drugs together. And I think this is going to mean that in the near future we might be able to deliver these more effective therapies in an even safer capacity.
I would say that the third area that was particularly exciting to me in late relapse where new CAR T-cell therapies are developing, in particular one called anito-cel, and this was a CAR T-cell therapy that has a bit of a different design than the previous ones. It seems to have a just as effective or meaning a high response rate we've seen with previous CAR T, but not as many of the side effects, in particular, the neurological side effects. Now, maybe too early to call this, but it's remarkable to see this because we want to deliver these drugs more safely.
Lastly, the fourth abstract I'm going to reference was called the RedirecTT-1 trial, and this is where we combined teclistimab, a bispecific antibody, and talquetamab, another bispecific antibody, and give them together in a group of patients that historically have very difficult myeloma to treat, patients with what we call EMD, or extramedullary disease. This is where the disease is outside of the bone, and we've known historically it's very hard to control this. Remarkably, when these two drugs get put together to treat EMD, we saw an over 80% response rate, something we've really not ever seen before in myeloma, and this could give us a great option in very challenging situations to treat multiple myeloma.
So let's summarize this and put it all together. In frontline therapy, we've clearly moved to quadruplets, we're moving towards dual-maintenance therapy, and we might even have MRD-guided approaches in the near future. In early relapse, belantamab is back and we're almost definitely going to be using it soon. And in late relapse, we're seeing extraordinary outcomes of CAR T-cell therapy, where a third of patients stay in remission for over five years. These are developments in multiple myeloma that we have not seen before and ones that we can truly be excited about.
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