For patients with refractory or relapsed KMT2A rearrangement or NPM1-mutations, the AUGMENT 101 study of the investigational menin inhibitor revumenib yielded impressive results.
According to an article in MedicalXpress, menin inhibitors are currently being developed to treat genetic subsets of acute leukemia.
60 patients were enrolled in the phase 1 trial including a ten-month-old baby. 46% of the patients had previously received a stem cell transplant. All patients in the trial had received at least four lines of therapy.
A Promising Response Rate
Of the 60 enrolled patients, 32 showed a response to revumenib, resulting in an overall rate of 53%.
18 patients went into complete or near-complete remission during a nine-month period. Of the 18 patients, 14 presented with levels of residual disease that were undetectable.
Dr. Ghayas Issa the study’s principal investigator at MD Anderson University in Texas, told MedicalXpress that many of the patients involved in the trial were doing so as their last hope.
For years, scientists have worked to prove that the menin protein is vital to specific leukemia subtypes. They suggested that if menin were targeted with a therapy such as revumenib, positive clinical responses will follow.
The study results were published online March 15th in Nature.
There is currently no approved targeted therapy for the two genetic subtypes of acute leukemia. 30% of leukemia patients harbor the NPM1 genetic alteration while rearrangements of KMT2A are evident in approximately 80% of infants with acute lymphoblastic leukemia (ALL) and about 15% of adults and children with both AML and ALL.
The prognosis for patients with acute leukemias and KMT2A rearrangements is very poor averaging five-year survival rates of under 25%.
In these two subsets, the menin protein interacts with KMT2A, driving leukemia-promoting gene expression and shifting gene expression in the cancer cells from leukemia to a normal pattern resulting in remission.
In other words, by targeting menin the gene transcription machinery is disturbed resulting in a protein formation.