An experimental drug for advanced or resistant acute myeloid leukemia has, in a small clinical trial, achieved some degree of remission in 53% of patients and complete remission in 30% (18 people), although possible signs of remission have also been detected. resistance to treatment.
Two studies published today in Nature present the results of a clinical phase 1 trial involving 60 people who were treated with the experimental oral drug revumenib, which “has revealed anticancer effects and possible evidence of resistance"says the magazine.
The first study, led by Ghayas Issa of the University of Texas, showed that inhibition of a protein called menin using revumenib “produced encouraging responses” in advanced acute leukemias with mutant KMT2A or NPM1 rearrangements.
"I am encouraged by these results, which suggest that revumenib may be an effective oral targeted therapy for patients with acute leukemia caused by these genetic alterations,” Issa said in a university statement.
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, showed a complete remission or complete remission with partial haematological recovery, the study indicates.
Of those 18 patients with complete remission, 78% had undetectable measurable residual disease after almost two months of remission, “demonstrating the potential of menin inhibitor therapies for acute leukemia,” the researchers write.
“These response rates, especially the rates of clearance of residual disease, are the highest we have seen with any monotherapy used for these resistant leukemia subsets."Issa noted.
The second of the studies, 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 lead to resistance to revumenib treatment through disruption of the drug binding site.
These mutations were detected in several patients who initially responded to revumenib treatment but did not maintain clinical response.
Identifying these escape routes from treatment provides valuable information that will be needed to improve patient outcomes in the future, according to the publication.
Acute leukemia is usually characterized by either the nucleophosmin 1 (NPM1) gene mutation or the mixed lineage leukemia 1 (KMT2Ar) gene rearrangement, both of which have been shown to contribute to cancer progression.
Overall survival rates are low, and there are currently no approved treatments that specifically target these genetic alterations.
Previous preclinical studies had shown that menin protein facilitates the progression of acute leukemia with KMT2Ar or NPM1 mutation, indicating that inhibition of this protein could reverse cancer progression in this subset of leukemias.