Acute Myeloid Leukemia - Episode 16

Case 4: Additional Considerations in High-Risk de novo AML

June 19, 2019


Naval G. Daver, MD:In the next slide, we’re going to discuss the other drug that has also been approved, low-dose cytarabine with glasdegib, and also a novel Hedgehog pathway inhibition, which has been used in many solid tumors. In heme, this is the first drug to be approved in that indication. As Dr McCloskey was discussing, we also were part of this trial and participated in it. Actually, the tolerability of this agent is quite good. I think this could be an agent that will be built on further, building on the combinations that are already being used. The study was a randomized study. It was a 2-to-1 randomization, and you see that the overall response rates were not as high as we see with the HMA/VEN [hypomethylating agent/venetoclax] but definitely better than low-dose cytarabine alone— about 22%, 23% compared [with] 5%. It’s definitely a meaningful option, especially in, let’s say, very old patients where you may be concerned about even [azacitidine/venetoclax]. If you have an 85-year-old who’s very fragile, those are the people where single-agent oralIDH inhibitor or low-dose Ara-C [cytarabine]/glasdegib could be something to consider, because they’re actually very well tolerated.

The survival data, as shown in this next slide, was met, 9 months versus 5 months, and this did lead appropriately to the FDA approval of this agent. Of course, this agent is being evaluated now in multiple phase II studies. One of them is with 3+7 [cytarabine/daunoribicin], which I think will be very interesting, because other than midostaurin, which is approved there, and gemtuzumab, maybe for the favorable risk, that is still an open space. If the glasdegib addition shows a benefit in those non-FLT3, non-core binding, that could actually be an open area. It’s also being looked at with [azacitidine], but a lot of that is outside the United States, because here, [azacitidine/venetoclax] has become one of the things used very frequently.

The last slide is looking at gemtuzumab. We briefly discussed this. I think our practice at [The University of Texas] MD Anderson [Cancer Center] has been the same as what Dr Rizzieri mentioned. We do use this for all our core binding factor patients across the board, and we are very happy with the benefits seen. The MRC [Medical Research Council] has published on this. The ALFA group has published. We’ve published on it. There is a single-agent gemtuzumab frontline approval, believe it or not. This is even less discussed than the glasdegib. Again, you’re talking about 5 months versus 2-and-a-half months. It’s very hard to see what patient would fit in this. I personally have never done it or seen it being done at our center, but it’s out there. I think the big use is with core binding factor and potentially in relapse. The good thing is, at the 3-per-meter-squared fractionated doses, the VOD [veno-occlusive disease] incidence is very low, and we actually have not seen it so far. Hopefully, that will continue. With that, I will stop our discussion here. Does anybody else have any thoughts or important things to mention? Anything else?

David Alan Rizzieri, MD:Great discussion.

Naval G. Daver, MD:Great discussion. Well, thank you all very much. I think this was a very nice panel. Thank you all. With this, I will specifically thank Dr McCloskey, Dr Rizzieri, Dr Weinberg, Dr Gergis. I agree; it was a very good discussion. For all of you in the audience who were listening to this and sat through 1-and-a-half hours of this very enthralling AML [acute myeloid leukemia] discussion, thank you all very much.

Transcript edited for clarity.