One in ten adults and children with a form of acute leukemia has a so-called KMT2A rearrangement. This error in the DNA leads to an aggressive form of the disease with often a worse prognosis. A clinical trial with the new drug revumenib took place to investigate safe dosing and effect on the disease for the group of patients in whom the disease has recurred or who did not respond well to standard treatment. Revumenib is a drug that turns off the KMT2A abnormality.
Worldwide
Prof. Dr. Michel Zwaan, research group leader and one of the heads of the Trial and Data Center, led the Máxima's participation in this study. 'A total of 94 patients worldwide participated in this phase 2 study, including 23 children. Five children received the drug revumenib at the Máxima Center within the study. In the first clinical study on the safe dose of revumenib, we already saw some children go into remission, which was very positive news. In this second study, the efficacy was confirmed and we saw 23% of treated patients go into remission. Compared to the previous 10% from the so-called historical results with chemotherapy, that is a very good progress.' Nearly 65% of patients who received revumenib during the study responded. The results showed no difference between adults and children. Children received a modified dose of the drug.
New drug class
Revumenib is part of a new class of drugs: the menin inhibitors. The menin protein plays an important role in activating the KMT2A abnormality, resulting in growth of leukemia cells. By specifically blocking the menin protein with revumenib, the leukemia cells disappear in some of the patients.
Besides being effective, the drug also has a positive effect on the quality of life during treatment. Zwaan: ‘Revumenib is taken orally and does not cause nausea. As a result, in a possible future treatment protocol, it could even be given on an outpatient basis.'
Treatment protocols
Ultimately, Zwaan hopes to incorporate these agents, along with chemotherapy, as a phase 3 study into treatment protocols for children with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) with such genetic abnormalities. And thereby be able to cure more children with these diseases. 'This type of drug could be very important for AML where you see that some children with a KMT2A abnormality have a very poor prognosis. Also in acute ALL in infants you often see this abnormality, and menin inhibitors could potentially play an important role in the future.'
New clinical trial
To further investigate treatment options with menin inhibitors, a new clinical trial will soon start at the Máxima Center. This study aims to determine the safe dosage of the drug ziftomenib, developed by the American pharmaceutical company Kura Oncology, for children with ALL and AML with various specific genetic disorders. This study is led by Zwaan's research group and coordinated by the Trial and Data Center at the Máxima Center in collaboration with the American Leukemia Lymphoma Society.
More information
The present international clinical trial was funded by Syndax and led by this pharmaceutical company. Participation from the Máxima Center was led by Prof. Dr. Michel Zwaan.
Would you like to read the scientific publication? Please look here: Issa GC, et al. Menin Inhibition With Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101). J Clin Oncol. 2025 Jan;43(1):75-84.