Results from the GMMG Concept Trial in Germany | Lisa Leypoldt, MD | IMS 2023

So my name is Dr. Lisa Leipold from University Medical Center in Hamburg, Germany, and currently also I'm at Dana-Farber Cancer Institute in Boston, Massachusetts. I presented at this International Myeloma Society meeting the results of our GMMG concept trial. This is a clinical trial that took place or takes place in Germany in 17 academic centers, and it's also an academic trial. We call it investigator-initiated, so it's actually from doctors who invented it, sort of, and not pharmaceutical sponsored. The trial was directed solely at patients with so-called high-risk newly diagnosed multiple myeloma. So high-risk is defined by certain markers in the myeloma cells itself, their genetics, so these are changes which do not affect the whole body but only the myeloma cells, and in combination with some certain blood markers, which we call a stage according to the International Staging System. In the trial, I looked at how a certain treatment achieves good or deep remissions in patients. The treatment we looked at was a quadriplet, so consisting of four drugs, each with a different mechanism of action. The treatment regimen is called ISA-KRD because ISA is isotoxin, which is an antibody, like that's directed against a marker on the surface of myeloma cells, and then cartilagin, which is, we call it a proteasome inhibitor, so it's directed at some target inside of the myeloma cells, which it blocks, sort of, that's very general, the mechanism. Then lanomidomide, which is an immunomodulatory agent, so interacting also with immune functions or immune system, and dexamethasone, a steroid, which is probably the most familiar. This quadriplet treatment was given to these patients for six cycles, each cycle was one month in length, for what we call induction, that's the first phase where you want to really get down the tumor load and tumor burden. And then afterward, those patients who were a little younger and fit underwent a high-dose treatment, those who were not received traditional cycles of this treatment, and then all patients received another four cycles of consolidation, and afterwards they went into what we call maintenance where they were getting still three of the four drugs, so ISA-KR for two years. And the trial was now looking at a time point after consolidation, so that's about 12 to 15 months after the treatment started, and was looking at how deep the remission was, basically. And we measured this by what we called MRD negativity, that's short for minimal residual disease or also measurable residual disease, and you can maybe imagine it like, you know, like if you were looking under a microscope, you can see more than if you're looking with your eyes. And if you then take other additional techniques, which we call flow cytometry, for example, and you can have an even deeper look than sort of a microscope. So with this technique, we could identify one or less than one tumor cells in 100,000 cells. And if this happened, or if we couldn't see any such, it was called MRD negativity. And by now it is known that the achievement of MRD negativity is very important, because patients who do get into these deep remissions tend to do better with their survival and, you know, how long the disease is under control. And in our trial, and all of these high-risk patients, which usually have a very poor prognosis unfortunately still today, we could see that about two-thirds of the patients were transplant eligible, so underwent the transplant, and more than half of the patients who did not undergo the transplant achieved this MRD negativity at the end of consolidation. When we looked at any time on trial, we saw that these rates were as high as 82% and almost 70% for the transplant eligible and transplant non-eligible patients. So very high rates. And these remissions were also durable, because in, again, almost two-thirds and almost half of the patients, or with the eligible and non-eligible, these negative remissions lasted for at least or more than one year. So that's very, very promising, because we hope it translates into a better survival. And then also we looked at the survival, and there we saw that after almost four years for the transplant eligible still, more than half of the patients, clearly more than half of the patients have not yet had a relapse of their disease. So the disease is still very well controlled, which is very promising. And for the patients who did not undergo the transplant, the time period was a little shorter, So there it was more like three years of follow-up, which we call it. But also after this time, it was basically very similar. So also there, more than 50% of the patients, clearly more, were still in this remission. So of course, we still aim to further improve these results. To date, those are ones of the best achieved so far with this intensified quadriplet treatment.