A experimental drug for the advanced acute myeloid leukemia or resistant has achieved, in a small clinical trial, some degree of remission in 53% of patients and complete in the 30% (18 people), although they have also been detected possible signs of resistance to treatment.
Two studies published today by ‘Nature’ present the results of a trial in clinical phase 1 in which they participated 60 people who were treated with the experimental drug by mouth revumenib, that “has revealed anticancer effects and possible signs of resistance,” the magazine notes.
The first study, led by ghayas issa from the University of Texas, showed that the inhibition of a protein called menin thanks to the use of revumenib, “produced encouraging responses” in advanced acute leukemias with KMT2A rearrangements or mutant NPM1.
“I am encouraged by these results, which suggest that revumenib It may be a effective oral targeted therapy for patients with acute leukemia caused by these genetic alterations”, Issa said in a statement from the university.
During the clinical trial, carried out between 2019 and 2022, Of the 60 patients, 53% had some degree of remission and 30%, that is, 18 patients, they showed a complete remission or complete remission with partial hematologic recovery, the study notes.
Of those 18 patients with complete remission, the 78% had undetectable measurable residual disease after almost two months of remission, which “demonstrates the potential of menin inhibitor treatments for acute leukemia,” the researchers write.
“These response rates, especially the residual disease clearance rates, are the highest we have seen with any monotherapy used for these subsets resistant leukemia,” Issa said.
second study
The second study, led by Scott Armstrong of the Dana Farber Cancer Institute (USA), delved into the appearance of selective resistance to menin inhibition.
The team identified specific mutations in the MEN1 gene (encoding menin), which can cause endurance to revumenib treatment by alteration of the drug binding site.
These mutations were detected in several patients who initially responded to revumenib treatment but who they did not maintain the clinical response.
The identification of these escape routes of the treatment provides valuable information which will be necessary for improve future patient outcomes, according to the publication.
Acute leukemia is often characterized by nucleophosmin 1 gene mutation (NPM1) or the mixed lineage leukemia 1 gene rearrangement (KMT2Ar), and both have been shown to contribute to cancer progression.
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The overall survival rates are low and there are currently no approved treatments that target specifically to these genetic alterations.
Studies preclinical Previous studies had shown that the menin protein facilitates the progression of acute leukemia with KMT2Ar or NPM1 mutation, indicating that its inhibition could reverse cancer progression in this subset of leukemias.