Adding Venetoclax to 7+3 Chemotherapy in Newly Diagnosed AML | Ioannis Mantzaris, MD | #ASH24

Yes. Hi. I'm Ioannis Mantzaris. I’m one of the, leukemia physicians at the, Einstein Montefiore Comprehensive Cancer Center in, Bronx, New York. I was the Pi in the clinical trial we presented on Saturday on the combination of venetoclax and 7+3 intensive chemotherapy for patients with newly diagnosed AML.

And I'm leading the clinical research, for that, our institution, this was an early phase trial, phase one with, study of another collects in combination with seven and three. seven and three is an acronym for the two different chemotherapeutic agents we use in acute myeloid leukemia for the patients that are young and fit to tolerate, intensive chemotherapy.

We've been trying to, to improve upon the results. The 7+3 alone has produced for years in the in this disease but the addition of venetoclax, which is a pill has been, recently introduced in the armamentarium of acute myeloid leukemia. It's revolutionized the therapy for older, unfit patients, the ones that cannot take intensive chemotherapy.

So we now taking that, advanced from, from the older patients and moving it to the, the young and fit patients with acute myeloid leukemia. Combining the venetoclax and the previous, standard of care of seven and three. And we wanted to see how first, how it's going to be tolerated, whether we're going to add additional toxicity or not, and whether eventual it’s going to help, the regiment produce better results.

So what we found in terms of success was a primary end point. We wanted to make sure that first it’s well tolerated. We did not see a signal of increased toxicity by adding Venetoclax to 7 and three. We did that in a dose escalation fashion. As such, attempts like ours have been, recently, attempted by other groups as well.

And, you know, the venetoclax duration has been variable and in an arbitrary way. So other people have used seven days or eight days or 11 days or 14 days. So we did that in a systematic fashion, in a way, in a dose escalation, 8 days, 11 days, 14 days, and no matter what the duration we use during the initial phase, we do not see any signal of increased toxicity with adding venetoclax to seven and three.

And importantly then as a as the next step, did it work? We did see, a significant signal of efficacy. Now these again are early stage trials. And the large randomized comparative trials the ones that, you know, half of the patients take one approach, and the other half are taking the novel approach. And then at the end we're comparing survival, which is what we want to see.

Usually these are this was an early phase trial. We tried to identify safety and then preliminary signals off of the combination working better. And for that we used as an end point. A significant end point is that the quality of the responses, the depth of the responses, you know, in acute leukemia, we're looking at those blood cells and leukemia cells with a microscope.

How many of them are left back when we give someone a therapy? And then above and beyond what I can see more sophisticated testing to identify cells at the very low level that could potentially, in the future, become a problem. And so we call that MRD or measurable residual disease. And with a central way.

So, so that we can limit, operator dependance, ability to identify these MRD, we use them or the assessment centrally. So one laboratory so that we can minimize buyers from different operators. And, we saw a very high numbers of MRD negative, complete remission, so high quality, the, remissions at the end of that, 7 and 3 of venetoclax scores that patients receive.

And so this is, a signal finding, of of high preliminary efficacy of combining the two. So I guess that summarizes, the results of our study.

I certainly hope so. And actually, I know so that, it's moving on to, to more advanced, stage of, trials. There is this, group of trials that is NCI, sponsored. It's moving to the phase two stage. This is one step further, again, with MRD being the primary endpoint to identify efficacy this time around, and in different patient population 7 and 3 and ven becomes one of the arms, to explore.

So certainly moving forward and, and I think it’s going to be one of the therapeutic alternatives for, for future. And maybe it will challenge the current standard of care. Yeah.