iwAL 2019 | How best to utilize emerging therapies for AML

Richard Stone

Richard Stone, MD, of the Dana Farber Cancer Institute, Boston, MA, talks about the current unanswered questions in the treatment of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), including how best to use promising therapies effectively. This video was recorded at the International Workshop on Acute Leukemias (iwAL) 2019, held in Barcelona, Spain.

Transcript (edited for clarity):

Richard Stone:                 Now in AML, we heard a lot of discussion, especially just now, about new therapies in AML. We learned … and now we have an embarrassment of riches, and the challenges and many unanswered questions of how to best use these. We have FLT3 inhibitors. We have [midostaurin 00:03:32] to be used with chemotherapy in the upfront setting, maybe [quizartinib 00:03:37] that will be approved in a similar setting there. We have [Gefitinib 00:03:40] and probably quizartinib to be use in relapse for three patients.

Richard Stone:                 We have [Axitinib 00:03:44], plus [venetoclax 00:03:45] or [Decitabine 00:03:45] plus venetoclax, or low dose [AC 00:03:49] plus venetoclax, to be used in our older unfit patients, and the idea is if you have some of the unanswered questions just to a few, if you have an older, unfit patient who’s also got a FLT3 mutation or an IDH1 mutation, should you use, like for example, for an IDH mutation, right now, you could use a single agent IDH inhibitor. You could use IDH inhibitor plus venetoclax. You could use venetoclax and an agent without an IDH inhibitor. Possible, all three together.

Richard Stone:                 What should we do? We don’t really know whether the mutations will inform all that. Category, that’s just one example of many questions.

Richard Stone:                 We also, and finally, the third aspect that got a lot of attention yesterday, very exciting attention, about how we use measurable residual disease.

Richard Stone:                 In AML there are two chief ways, maybe three chief ways, to measure disease beyond the level of the light microscope. One is flow cytometry to identify a signature of the leukemia cell, that we can see again when the patient’s in clinical remission.

Richard Stone:                 Two is PCR based and we have a target like NPM1 mutant AML. We can measure the NPM1 mutation, very sensibly, using PCR techniques. Been validated by our British colleagues Dr. Ivy and the late [Dr. Grim White 00:05:07]. And so, should we be using that routinely to measure outcome of patients.

Richard Stone:                 And thirdly, we have NGS techniques, which was talked about at length by [Dr. Volk 00:05:16] yesterday, from the Netherlands, about the importance of measuring residual mutations at the time of remission, but not all mutations are creating equal.

Richard Stone:                 For example, the DNMT3A tattoo and DNMT2A mutations, DNMT3A tattoo and SX1 mutations, when they persist entire remission, don’t seem to carry the same bad prognostic implications as the other mutations. Although, [Dr. Metzler 00:05:41] called into question, that’s still a bit controversial.

Richard Stone:                 So, I think, how to use MRD. Should we react to it by doing a transplant if we see it, even in a patient who otherwise wouldn’t be transplanted because they have [fable risk 00:05:54]? Or should we not do a transplant on somebody’s who’s got bad risk disease based on genetics and cytogenetics? And even if they responded well, should we still not transplant them?

Richard Stone:                 So there’s many questions about how to manage AML and even ALL today, which we’ve begun … we’ve got some good thoughts about that from this meeting, but we’ll need to do additional clinical research to be able to really understand the right way to go.


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