Experimental drug achieves remission of acute leukemia in 18 patients
A experimental drug for myeloid leukemia. advanced or refractory acute myeloid leukemia has achieved, in a small clinical trial, some degree of remission in 53% of patients and complete remission in 30%. (18 individuals), although possible signs of resistance to treatment have also been detected.
Two studies published today in Nature present the results of a phase 1 clinical trial in which 60 people participated who were treated with the experimental oral drug revumenib, which “has revealed anticancer effects and possible indications of resistance.”the journal notes.
The first study, led by Ghayas Issa of the University of Texas, showed that inhibition of a protein called menin through the use of revumenib, “produced encouraging responses.” in advanced acute leukemias with KMT2A or mutant 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, conducted between 2019 and 2022, 53% of the 60 patients had some degree of remission and 30%, or 18 patients, showed either complete remission or complete remission with partial hematologic recoverythe study notes. Of those 18 patients with complete remission, 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.
The second of the studies, led by Scott Armstrong of the Dana Farber Cancer Institute (USA), delved into. the emergence of selective resistance to menin inhibition.. The team identified specific mutations in the MEN1 gene (encoding menin), which can cause resistance to revumenib treatment Through alteration of the drug binding site.
These mutations were detected in several patients who initially responded to revumenib treatment but did not maintain clinical response. Acute leukemia is usually characterized by the nucleophosmin 1 (NPM1) gene mutation. or the mixed lineage leukemia 1 gene rearrangement (KMT2Ar), and both have been shown to contribute to the cancer progression.
The Overall survival rates are low and there are currently no approved treatments. that specifically target these genetic alterations. Previous preclinical studies had shown that the menin protein facilitates the progression of acute leukemia with KMT2Ar or NPM1 mutation, suggesting that inhibition of this could reverse cancer progression in this subset of leukemias.