A randomised trial of the FLT3 inhibitor gilteritinib as post-transplant maintenance for FLT3-ITD AML

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Published: 16 Jun 2023
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Dr Mark Levis - Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, USA

Dr Mark Levis speaks to ecancer at EHA 2023 about a randomised trial of the FLT3 inhibitor gilteritinib as post-transplant maintenance for FLT3-ITD AML.

He explains that results show that there is an apparent benefit of gilteritinib but that it did not reach statistical significance.

Dr Levis explains that they made an assumption that not everyone would benefit but that they were intending to find out who would benefit. Those who showed MRD around the time of transplant showed best benefit.

The MORPHO study was a double-blind, randomised, placebo-controlled trial to test really two things: first, do all patients with a FLT3-ITD AML who are going to transplant benefit from post-transplant maintenance therapy with gilteritinib? The second very important question is can we use measurable residual disease to determine who benefits, on the assumption that not everybody is going to benefit?

The trial was conducted worldwide over really about a three-year period. Results show that there actually is an apparent benefit overall, but it did not reach its predetermined level of statistical significance at 0.05. It missed it by a whisker, 0.0518, but really those of us that designed the trial designed it to tell us how to use these drugs. We made the assumption that not everyone would benefit and, in fact, we were labelled by some as unethical for running such a trial because many people thought the issue was already settled and everyone should get FLT3 inhibitor. Whereas, in fact, the pretrial hypothesis that MRD would tell us who benefits was exactly correct, and the Kaplan-Meier curves split perfectly along those lines with clear benefit for those patients who had MRD around the transplant time versus no benefit for those who didn’t. 

In addition, we’ve uncovered causes of toxicity, intolerability, things that we can use to guide clinicians in using these drugs going forward, so there’s a tremendous amount of data that’s going to come out from this trial, not just that MRD positive patients get the drug.

How might this research impact future treatments?

This was the first example where we used MRD to truly guide a specific therapy. In addition, we have demonstrated that a FLT3-ITD mutation is an acceptable marker for MRD, it used to not be considered that. So at this point now, we have to start using this MRD approach for these patients to guide future therapies, future drug development.