ASH 2025 | VICEROY study: azacitidine, venetoclax, and gilteritinib in FLT3-mutated AML

The VICEROY study is a very important study that looked at the frontline combination of azacitidine, venetoclax, gilteritinib, and newly diagnosed FLT3 mutated AML who are considered to be not suitable or unfit for intensive chemo. So the background of this study is we at MD Anderson about four years ago started evaluating adding FLT3 inhibitors to the established AZA, Ven, and gilteritinib regimen through the VLA study that was led by Dr Donato at MD Anderson. What we saw in the VLA is that although the remission rates were 67% in FLT3 mutated, the duration of remission was short, about six to seven months, and median overall survival was only 12 months in older patients who got AZA, Ven for a FLT3 mutated disease. So we needed to improve on this. We had very potent FLT3 inhibitors like gilteritinib available. And so this was added to the backbone of AZA and Ven. And that triple combination of AZA, Ven, and gilteritinib published by Nick Short in JCO last year showed very striking remission rates. CR rate of 70% compared to about 40% CR rate seen with AZA and Ven and CRc rate of 95%. And also the median overall survival was about 26, 28 months. So more than double of the 12 months that was seen with AZA and Ven from VLA and FLT3 mutated. So based on that, the VICEROY was then developed as a multicenter, sponsor-supported study to use the same regimen and evaluate if we can get similar results as the MD Anderson experience. Overall, in fact, we did get very similar results. We see that the combination of AZA, Ven, and gilteritinib, the multicenter setting does give about a 90% CRc rate, about a 70-75% CR rate. Median overall survival at this time is 23-24 months, but the follow-up is ongoing and it may actually hopefully improve over time. And the regimen is well tolerable. One of the key points though, both in the MD Anderson study and the VICEROY, is that we actually reduce the amount of venetoclax compared to the standard label. We use a day 14 bone marrow to get an early assessment of marrow myelosuppression or ablation. And if patients achieve marrow ablation or suppression by day 14, we stop the venetoclax by day 14, as well as the gilteritinib. And in fact, this approach seems to give us still very high, more than 90% remission rate, good durability, but mitigate myelosuppression with count recovery of about 38 to 39 days, which is very similar, maybe two, three days longer than you get with AZA and Ven. So there is a bit of an art and detail as to how the dosing is developed and given. It’s not just standard AZA and Ven added with gilteritinib. It is dose modifications. But with that approach now, which has been published and presented with 14 days of Ven, 14 days of gilteritinib, azacitidine, and moving forward in the next cycle, it’s further reducing the venetoclax needed. We’re seeing very, very high efficacy, depth of response, duration, and looks like maybe even getting more than double survival in the FLT3 compared to what we would expect with azacitidine. So this study is ongoing and we’ll move to the phase two and hopefully further expansion, but I think could be a very important study that eventually over time, hopefully could change practices across the country. I know many of my colleagues I spoke to are already using this regimen or very similar variations of this regimen, adding FLT3 inhibitor to AZA and Ven in their frontline patients. And as the VICEROY data hopefully continues to mature, this will become more and more standard in the future is our hope.

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