Acute Myeloid Leukemia: Evolving Through Targeted Therapies - Episode 7

Optimal Use of Venetoclax in AML

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Harry Paul Erba, MD, PhD: Twenty percent of the patients in the VIALE-C trial with Ara-C [cytarabine] did have prior HMA [hypomethylating agent] exposure. But I’m not convinced, Gail, that that’s enough to explain the lower response rate in the shorter median survival of the venetoclax combination with Ara-C [cytarabine] than HMA.

Gail J. Roboz, MD: That’s the primary criticism: Is that number enough? I’m definitely not in any way trying to argue that the data are as robust as they were for the other studies. I’m not trying to argue that.

However, I do think the response rates—having participated strongly in that study and watched the patients—are definitively better than for low-dose cytarabine alone, which are pretty crummy. There was enough benefit in patients as you go individually that one could imagine that it really was that short follow-up that prevented us from seeing the benefit. We’re trying very hard in a very rigorous academic way. Andrew Wei and I are trying to work on this to see if there’s any way to prove that point: Is this just a matter of statistics, or is it really not worth anything? We’re trying to answer that question as best as we can.

Daniel Pollyea, MD, MS: There is a nice figure, Harry, in the JCO [Journal of Clinical Oncology] paper of the phase 2 study, and they actually subtract out that subset of patients and then report the response rates. This isn’t survival but just response rates for patients who were truly treated and naïve. It’s hard to compare apples and oranges. But it gets close to the 60% range.

The other thing that may be a distinguishing feature—Andrew did a very nice talk about this at ASH [American Society of Hematology Annual Meeting] last year—is that perhaps the good subsets of patients who are highly responsive to venetoclax, the NPM1s, the IDHs, do as well with the low-dose cytarabine. It’s perhaps the tougher patients, the more secondary AML [acute myeloid leukemia] or the complex cytogenetics, or the genomically defined poor high-risk patients who aren’t doing as well with the low-dose cytarabine. Time will tell, but there may be ways to tease that out.

Gail J. Roboz, MD: The other thing to do, and you’re not supposed to mix and match these comparisons, but we have the availability of a low-dose cytarabine-based regimen in combination with glasdegib, which is actually proving to be a little difficult for discussion. People aren’t exactly sure what to do there. It does not look competitive with respect to these newly diagnosed patients who were treated with AZA-VEN [azacitidine-venetoclax]. But again trying to just understand: Are there some patients for whom a low-dose cytarabine-based regimen would be something you wanted to try? Trying to answer the question of which 1 you might pick. It certainly seems that the venetoclax-based with low-dose cytarabine had much higher response rate.

Transcript Edited for Clarity