Good Responses to Phase 2 CLIA + Ven Therapy for Acute Myeloid Leukemia | Tapan Kadia, MD | #ASH24

Hi, I'm Tapan Kadia. I'm currently a professor in the Department of Leukemia at MD Anderson Cancer Center in Houston, Texas. I'm really glad to be here at ash. Lots of great meetings and, one of the studies we're going to present is, a clinical trial, a phase two clinical trial that we’re doing at MD Anderson that's been going on for several years now, but we now have mature data that I'd like to share.

It's a regimen called Clia, Clia plus venetoclax. The clia is a chemotherapy backbone, for the treatment of newly diagnosed acute myeloid leukemia. And so it's composed of cladribine, idarubicin, And Ara C or cytarabine given in the clia regimen. Then we added venetoclax to that. And the background on that is that we've been using clia for many years because it allows the addition of cladribine with Cytarabine, to have, higher response rates in synergy in patients with AML.

Venetoclax, which is an oral drug that inhibits a protein called BCL two, became available for the use of in older patients with newly diagnosed AML with lower intensity therapy. So we hypothesized that the addition of Venetoclax to the clia regimen would actually improve response rates in young and fit patients and improve response rates. And so we, we combine the two reg, the two drugs, two regimens together.

And, we came up with clia and venetoclax. The study, allowed only patients under the age of 65 years because it is a very intensive regimen. As you know, as you get older, in age and also in your fitness, it's harder and harder to tolerate intensive chemotherapy. So that was selected for patients who are fit and who are under the age of 65.

The patients who received chemotherapy. What they found is with the first cycle chemotherapy, the complete remission rate, which is composed of complete remission and incomplete count recovery. Was, 94%. So 94% of patients who received one cycle of therapy achieved a complete remission, but with their acute myeloid leukemia. And on top of that, the, the depth of remission was outstanding.

So 89% of those patients would achieved remission had what's called an MRD negative remission. And this is a method to detect a very minimal residual disease at a very low level, down to 1 in 10 to the minus four. So a very deep remission just after one cycle of chemotherapy, about 65 to 70% of those patients were able to then go on to stem cell transplantation.

With the hopes that we can cure those patients. And now that we have long term follow up, almost two and a half years, we see that those patients who are treated on the program, their long term survival, out to two and five years is 75%. So 75% of those patients who started with AML on this regimen are still alive and in remission.

So, again, a very, meaningful, and, and hopefully, something they'll be taken forward in larger studies.

Nope. That's the challenge. I think that we have to get, several groups together to get started. But it's a regimen that's been used not only at our institution, but because of our publications that have been used, around the country. And around the world as well. You know, in the past, the remission rates with intensive chemotherapy were in the range of 60, 65% with these regimens with clia without venetoclax, they went up to about 80% now in 94% of patients are expected to get a remission with this particular regimen. Now it is an intensive regimen. So it's, it's definitely for those who are fit. We did see, myelosuppression or low blood counts in every single patient that we treated 100%. And that's expected.

We kept them in the hospital for the first month. There was a high rate of infections, serious infections like pneumonia. And bacteria in the blood and sepsis and things like that. That can happen, but they're all very well managed. In fact, the early mortality rate was only 1%, but only had one death in four weeks, which we, you know, in the past and back in the day, we should expect many more.

But with the use of antibiotics, with the use of growth factors like GCSF, we're able to see much, much better outcomes. And so although it is intensive, the response rates are very good. I think the take home message is that, the treatment of AML is evolving significantly. We used to use seven plus three, which is the standard regimen for 4 or 5 decades.

And everyone got the same regimen. I think in this day and age, we have specific regimens for specific subsets of people. And more and more, you're going to start seeing the addition of venetoclax to intensive chemotherapy regimens. The revolution of Venetoclax and HMA or vidaza has already happened. And it's and we're living in it.

It's great. Older people are getting therapy, but we're now, pushing that benefit into onto younger patients who are more fit. And we're going to see starting to see a revolution of intensive chemo and then as the next evolution of AML treatment.