Eighteen patients affected by blood cancer are in remission after receiving revumenib, an experimental treatment, during a trial.
- Revumenib is a small molecule inhibitor of the menin-KMT2A interaction.
- In a phase 1 trial, conducted among 68 people suffering from acute leukemia, this treatment made it possible to cure 18 patients.
- The most common drug-related side effect was asymptomatic prolongation of the QT interval on the electrocardiogram.
3.428. This is the number of new cases of acute myeloid leukemia (AML) estimated in 2018 in France, according to Public health France. This blood cancer is “the most common type of leukemia in adults, although it is seen at any age”indicates the MSD Manual. In this disease, cells that normally grow to be white blood cells become cancerous and quickly replace normal cells in the bone marrow.
“Acute leukemias are difficult to treat”
Recently, researchers at MD Anderson Medical Center (USA) revealed that a drug, called revumenib, showed encouraging results against acute myeloid leukemia. To achieve this discovery, they performed a phase 1 clinical trial. “Acute leukemias with KMT2A rearrangements are difficult to treat, and NPM1 mutations are the most common genetic alteration in acute myeloid leukemia. These subsets do not benefit from specifically approved targeted therapies,” said Ghayas Issa, who led the study published in the journal Nature.
68 patients with acute leukemia received revumenib
As part of this work, the scientists wanted to assess the safety and antitumor activity of revumenib, a small molecule inhibitor of the menin-KMT2A interaction. For this, they recruited 68 patients aged around 43, including children aged 10 months. 82% of the volunteers suffered from acute myeloid leukemia, 16% from acute lymphocytic leukemia and 2% from acute leukemia with a mixed phenotype. Among them, 67.6% had KMT2A rearrangements, 20.6% NPM1 mutations and 11.8% other genotypes. Before participating in the trial, the adults and children had already received heavy treatments and undergone an allogeneic stem cell transplant. In this study, they received revumenib by mouth every 12 hours for 28 days.
Revumenib achieved complete remission in 30% of patients
“We show that this treatment was associated with a low frequency of adverse effects and a 30% rate of complete remission or complete remission with partial haematological recovery”, the authors said. The most common drug-related side effect was asymptomatic prolongation of the QT interval on the electrocardiogram. Other reactions included diarrhea (3%), fatigue (3%), anemia (3%), tumor lysis syndrome (2%), neutropenia (2%), thrombocytopenia (2%), hypercalcemia (2%) and hypokalemia (2%).
“The responses obtained in this trial show that menin inhibitors may constitute a promising therapeutic option, well tolerated by patients, and that they could be the new adjunct to effective targeted therapies against acute leukemia”, explained Ghayas Issa in a statement. Now, recruitment for phase 2 of the trial is underway. Future research on revumenib will test combinations with other agents in different settings.