Combinations are the Future in FLT3-Mutated AML - Episode 12

Emerging Combinations for FLT3-Mutated AML


Jessica K. Altman, MD, and Naval G. Daver, MD, review novel combinations under investigation for the treatment of FLT3-mutated acute myeloid leukemia.

Naval G. Daver, MD: In the last few minutes we can discuss new combinations and targets. You and I are working on some combinations with PD-L1, MDM2, as well as are exploring other pathways to combine with our new FLT3 inhibitors. What do you see as exciting for FLT3-mutated disease in the next 5 years?

Jessica K. Altman, MD: That’s a great question, Naval. Thank you. I think we’re going to continue to work our way through new FLT3 inhibitors. There’s the Fujifilm Wako Pure Chemical Corp compound, and Aptose Biosciences, Inc has a compound. And there are others. I also think we now have the wisdom and the view to look beyond FLT3. As we’ve mentioned, as we gain a better understanding of mechanisms of resistance, thinking about how patients relapse outside of FLT3, I think menin inhibitors and other agents should be explored in this setting.

What about you? What excites you in this field?

Naval G. Daver, MD: When we speak to the companies, they say, “Oh, is there room?” Yes, absolutely. I know this is the third time I’m bringing it up, but I think the CML [chronic myeloid leukemia] story is a cool story. Three years ago we said we had a fifth TKI [tyrosine kinase inhibitor]—ponatinib. We said, “OK, this is done.” But in fact, no. We saw asciminib. There’s another one from China that is looking very active, and then there’s an eighth one. Those 2 or 3 drugs may add new things to the landscape. And just like everything else, science is moving at a logarithmic pace. It’s no surprise that some of these new drugs are going to be better compounds because they were developed 10, 15 years later. It’s tough though, because now we’re combining 3 drugs, and they have to find a single-agent strategy. It may take a lot of ex-US development in areas that don’t have all the drugs, or whatever. But I think we have to find ways to move them forward. Then, yes, that’s probably another very exciting next breakthrough area—the menin inhibitors. Even though it’s not a FLT3 inhibitor, I think it links, as you said. We know a lot of patients who have a FLT3 mutation may actually be sensitive. In the next couple of years, hopefully as these menin inhibitors find their own path, to single agent of course, as far as regulatory approval and things like that, then we can combine them.

Then there are other combinations with MDM2, PD-L1. I don’t know if they will have a unique role, but those are being looked at as well.

So with that, I think we’re at the end of this discussion. It’s been a great conversation. It’s always a pleasure to talk with my friend, colleague, and FLT3 expert, Dr Jessica Altman. Thank you very much, Jessica. I’m looking forward to many trials and improvements in the FLT3-mutated field.

In summary, FLT3 inhibitors are a major improvement in AML [acute myeloid leukemia], but we still have a long way to go. Novel combinations, novel sequences, and using them up front will hopefully further improve the outcomes. I would like to thank you all very much for listening. Stay safe, everybody. Bye.

Transcript Edited for Clarity