EHA 2026 | Revumenib after transplant shows promise in KMT2A-rearranged and NPM1-mutated AML

So we all know that revumenib is the first-in-class and the first approved menin inhibitor for relapsed refractory MLL2 and NPM1-mutated acute leukemias. The AUGMENT-101 was a pivotal trial which used revumenib as a monotherapy for relapsed refractory MLL2 and NPM1 patients. So our post hoc analysis was mainly driven for understanding how patients were doing when revumenib was restarted after a consolidative transplant. So these were patients who were enrolled on the trial, they received revumenib, they achieved a response and then went on to a transplant and restarted revumenib. A total of 19 patients were enrolled with a median age of 39 years, so these were young patients. 14 of those were actually MLL2 rearranged patients, so the majority of those were MLL2s, four patients with NPM1s and one patient with NPM1 rearrangement. What did we see? That the median time from transplant to starting maintenance revumenib was two months. So this was quite an early intervention. It could be done from day 30 until day 180. So the median was two months, around day 65. The median duration of revumenib was 20 months. Three patients are still on revumenib and have ongoing treatment. We were very happy to see that these highly pre-treated patients, so half of them were already after the first allo, half of them were already post venetoclax, and these heavily pre-treated patients went on a transplant to start revumenib, and their median relapse-free survival at 12 months was 78%. So we only witnessed four relapses. So this is, again, very important. Of course, when we are speaking about post-transplant patients, we always fear about additional toxicity of any intervention we do. So for revumenib, the main concern which we witnessed was thrombocytopenia, which was quite prevalent in almost 50% of grade 3 or 4 platelet reduction from the baseline. But importantly, this did not lead to withdrawal of revumenib. It did require dose interruptions or dose reductions. And the majority of patients had their platelets going up after three or four cycles of revumenib. So we’re very happy about these results. We did not see any differentiation syndrome. We only witnessed one grade two QTcF prolongation, which was not related to revumenib. So as for now, the signal seems to be good. The only concern we might see is the thrombocytopenia. But again, it could be managed and these patients can be on revumenib for a prolonged period and hopefully this will further improve their overall survival and relapse-free survival.

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