An experimental drug for advanced acute myeloid leukemia or resistant has, in a small clinical trial, achieved some degree of remission in 53% of patients and complete remission in 30% (18 people), although possible indications of resistance to treatment have also been detected.
Two studies published this week Nature present the results of a trial in clinical phase 1 in which 60 people participated who were treated with the experimental oral drug revumenibwhich “has revealed anticancer effects and possible signs of resistance,” the journal 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 reorders or mutant NPM1.
“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.
Of the 60 patients, 53% had some degree of remission and 30% (18 patients) had a complete remission.
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.
menin inhibitors
Of those 18 patients with complete remission, 78% had undetectable measurable residual disease after nearly two months of remission, “demonstrating 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 resistant leukemia subsets,” Issa said.
The second study, led by Scott Armstrong from 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 resistance to revumenib treatment by altering the drug binding site.
These mutations were detected in several patients who initially responded to revumenib treatment but did not maintain clinical response.
Identifying escape routes from treatment provides valuable information that will be needed to improve future outcomes, say the authors.
Identifying these escape routes from treatment provides valuable information that will be needed to improve patient outcomes in the future, according to the publication.
survival rates
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 currently there are 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.
References:
Ghayas Issa et al. “The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia”. Nature (March, 2023).
Scott Armstrong et al. “MEN1 mutations mediate clinical resistance to Menin inhibition”. Nature (March, 2023).
Fuente: EFE
Rights: Creative Commons.