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EHA 2025 | The impact of conditioning intensity on MRD in patients with FLT3-ITD AML undergoing alloSCT
Mark Levis, MD, PhD, Sidney Kimmel Comprehensive Cancer Center & Johns Hopkins School of Medicine, Baltimore, MD, shares the findings of a post-hoc analysis of data from the MORPHO (BMT CTN 1506) trial (NCT02997202). This analysis investigated the effect of conditioning intensity and concurrent NPM1 mutations on measurable residual disease (MRD) status in patients with FLT3-ITD acute myeloid leukemia (AML) undergoing allogeneic stem cell transplantation (alloSCT). Dr Levis highlights that the data suggest that myeloablative conditioning may not eradicate FLT3-ITD MRD more effectively than reduced intensity conditioning, and that patients with NPM1-mutated FLT3 ITD-AML do not derive benefit from myeloablation. This interview took place at the 30th Congress of the European Hematology Association (EHA) in Milan, Italy.
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Transcript
So we did a post-hoc analysis looking at conditioning intensity. Patients on that trial received either myeloablative or a reduced intensity conditioning. 60% received myeloablative, 40% reduced. And there is a general thought in the field of transplant that myeloablation is always better than reduced intensity conditioning if a patient can tolerate it. However, that’s again lumping all of AML into one category, and in fact it isn’t one disease...
So we did a post-hoc analysis looking at conditioning intensity. Patients on that trial received either myeloablative or a reduced intensity conditioning. 60% received myeloablative, 40% reduced. And there is a general thought in the field of transplant that myeloablation is always better than reduced intensity conditioning if a patient can tolerate it. However, that’s again lumping all of AML into one category, and in fact it isn’t one disease.
So when we looked at this by mutation subtypes, NPM1 again is a unique category of AML. The NPM1 mutations drive expression of FLT3 and tend to generate a FLT3 addicted clone. If you wish to decide whether or not to give myeloablation, you also need to take into account if the patient needs to have post-transplant maintenance with a FLT3 inhibitor. If they get myeloablation, it’s harder to do because the patient is often sicker and can’t start the drug sooner. And in fact, when we looked at this post-hoc analysis, patients with an NPM1 mutation didn’t benefit at all from myeloablation, irrespective of young or old. They really needed the FLT3 inhibitor.
So the post-hoc analysis suggests that for NPM1-mutated FLT3 ITD-AML, you should not be using myeloablation at all. But then that gets into the next component of the argument, myeloablation is supposed to eliminate MRD. Well, we had a direct way to test this. We had MRD measurements by this FLT3 MRD assay pre and post transplant, immediately before getting conditioning, immediately after. And so we asked the simple question, well, if myeloablative conditioning works so well to eradicate MRD, let’s compare MRD pre and post conditioning. We have myeloablative and non-myeloablative. And there was not a whit of difference between the two. Myeloablative conditioning did not eradicate MRD any better than reduced intensity conditioning. Again, turning that concept on its head, no, you’re wrong. Myeloablative conditioning may be a good idea for some, but not specifically for the FLT3-NPM1-mutated AML.
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