Advances in research against various types of cancer continue. A few months after learning of the success of the first trial of the drug Omomyc against the disease, Nature publishes two studies that encourage new and promising research: an experimental pill for acute myeloid leukemia has achieved complete remission of the cancer in 18 patients in a very serious due to an aggressive tumor that did not respond to other treatments.
The drug is called Revumenib and, although it is in its first phase of experimentation, it is achieving very promising results. As shown in the conclusions of the clinical trial, the pill has revealed “anticancer effects and possible indications of resistance.” Specifically, among the 60 participants, 53% of the patients achieved some degree of remission and 30% (18 people), complete remission. Additionally, 78% of patients achieved clearance of measurable residual disease.
Although the results are preliminary and do not imply a definitive cure, those responsible for the experiment have an optimistic view of the treatment.
The first study, conducted by Ghayas Issa of the University of Texas, showed that inhibiting a protein called menin, which is what facilitates the progression of leukemia, could be effective in treating cancers with these mutations. Thus, the drug seeks out and binds to menin to stop it. According to Issa, the inhibition of this protein alters the gene transcription machinery and changes the gene expression of cancer cells from a leukemic pattern to a normal one.
Acute myeloid leukemia affects the marrow of the bones (the factory for blood cells) and causes the runaway production of defective cells. The disease is the most common blood cancer in adults, with about 120,000 cases per year, and three-year survival barely reaches 25%.
It should be noted that the drug does not work in all cases, since the team at the University of Texas MD Anderson Cancer Center has focused on leukemias that meet two genetic variants: the so-called KMT2A and mutant NPM1. Leukemias with KMT2A rearrangements occur in infants, children, and adults. On the other hand, NPM1 mutations are the most frequent genetic alteration in acute myeloid leukemia.
The second study, 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 lead to resistance to Revumenib treatment.
These mutations were detected in several patients who initially responded to treatment but did not maintain the clinical response. Identifying these escape routes from treatment has provided invaluable information to research that will be needed to improve patient outcomes in the future.
Issa said that the responses obtained in this trial “demonstrate that menin inhibitors may be a promising therapeutic option, well tolerated by patients and could be the new addition to successful targeted therapies for acute leukemia.”
Revumenib’s efficacy and safety will continue to be tested in the Phase II trial, for which enrollment is now open. In the near future, combinations with other agents will be tested in a variety of settings, including newly diagnosed leukemias, relapsed or refractory disease, and maintenance therapy, for leukemias with the KMT2A or NPM1 mutation, and other leukemias amenable to menin inhibition.
