Adding Isatuximab to Standard RVD May Improve Outcomes for Myeloma Patients | Elias Mai, MD | #ASH24

Hello, my name is Elias Mai from Heidelberg University Hospital and I'm pleased to tell you a little bit about our phase 3 trial that was done in patients with newly diagnosed multiple myeloma who are eligible for an autologous stem cell transplantation. The trial is called GMMG-HD7 and we included over 660 patients that were randomized to receive either a standard treatment containing bortezomib, lenalidomide and dexamethasone, which is a common combination that is used in newly diagnosed multiple myeloma, or the same combination plus a novel immune therapy which is an antibody directed against CD38 and it's called isotaxima. The induction treatment was for a total of 18 weeks. So patients were randomized one to one, that means neither the patient nor the doctor could influence which treatment the patient received, but the patient was assigned by a computer to receive either the standard combination of bortezomib, lenalidomide and dexamethasone or the same combination plus isotaxima. In this update of the trial we looked whether patients had a longer time until their disease comes back, which we call a progression, or they died from any cause. So the aim was of course to show that this addition of isotaxima, this novel immune therapy, led to a longer time until the disease comes back or the patient dies from any cause as compared to the current standard with just these other three agents that I mentioned. Of note, after this 18 weeks of induction therapy, all patients received an autologous stem cell transplantation, which means that first their stem cells were harvested, their own stem cells, and then in the next steps they receive a high dose treatment, which is a very high dose of melphalan, a cytotoxic agent that's been used for over 30 years in the myeloma space and it's considered a gold standard, and then they become a re-infusion of the stem cells so that their whole blood system and everything can recover from this severe aggressive therapy, which is also eradicating the myeloma disease. So when we looked at the results of the trial, we found that for the majority of the patients, both treatments were very well tolerated, and the addition of this new immune therapy did not lead to any new severe side effects that were not handleable, so it was pretty well tolerated. Also it did not affect the recovery of the blood cells after the transplant, so that was working perfectly fine. We then looked, also besides time until the disease comes back or patients die, we looked at a very, very new technology, and this technology is called minimal residual disease. It requires a bone marrow puncture, and in that bone marrow puncture, which is painful and most of the patients, all patients needed for the diagnosis, but in the trial we also did it in the follow-up, and we looked after transplant as well, and we found, intriguingly, with this very sensitive technology, we can count single cells, up to millions of cells in the bone marrow that we took from an aspirate from the bone marrow, and we count these cells and we can look if there are single myeloma tumor cells left or not. And what we found was very interesting that almost 70% of the patients that were treated with this 18 weeks of isotoxin plus lenalidomide plus bortezomib plus dexamethasone had no malignant tumor cells in the bone marrow anymore after they received the additional transplant, and that was much more as compared to the patients that only received the combination of bortezomib, lenalidomide and dexamethasone plus the transplant, which was roughly about 47-48%. So this really, really increased the depth of response and the tumor cells in the bone marrow, that's where the tumor grows, were eradicated, which means they were killed and were gone. And as you can imagine, based on this difference that we see, we also observed, and that's what we will present at the meeting this year, we also observed that the time until the disease comes back in the patient or the patient is dying from any other cause was significantly and clinically meaningful, prolonged in the patients that received the addition of isotoxin up for these 18 weeks, which means that patients lived longer for several months. It was a significant, significant benefit for the patients that were treated with the isotoxin up. So my conclusions based on this are that this is a very, very relevant study because it's a large study, we included more than 660 patients, and it's among the first studies to show these therapies involving four agents are highly effective and really lead to a pronounced survival benefit in patients that receive these four treatments. One thing that is unique about our study is the fact that the patients receive all of these four drugs before transplant. And after transplant, they receive only a maintenance therapy in the trial, which was either consisting of the standard of care in all across the world, which is lenalidomide, or lenalidomide plus a continuation of the antibody isotoxin up, which was also given during induction. So in that regard, the trial is really unique and we'll be able to answer a lot of questions in the future because now we looked at the induction treatment and how that influenced the time until the disease comes back. And in the future, we will look at how the maintenance treatment will influence the time until the disease comes back. And this is unique for this trial. No other trial in the world will be able to look at that. And of course, I want to thank the patients who participated in this trial, and I have treated many of them and I'm very, very glad that most of them are doing very well and tolerated the treatment very well. And I'm also thankful for the families of the patients and the caregivers to the patients who helped us and of course, all the study sites that provided excellent support and many patients were treated across Germany. And this is a unique team effort. Thank you.