Mikkael Sekeres, MD, MS
Commenting on these studies of menin inhibitors, Mikkael Sekeres, MD, MS, Professor of Medicine and Chief of the Division of Hematology at the Sylvester Cancer Center, University of Miami Miller School of Medicine, was enthusiastic about the promise of these agents because they are targeted to specific genetic abnormalities in acute myeloid leukemia (AML). As in lung cancer, the incremental success of treating various smaller subpopulations with specific genetic abnormalities may add up to a larger proportion of patients with effective treatments.
“As we have learned more and more about the genetic basis of AML, the hope is this would translate to therapies targeting the biology of AML. Menin inhibitors are an example of this,” he said. “We are focusing on agents that are relevant for increasingly smaller populations of patients.”
First Revumenib
“The first study from MD Anderson was slightly larger and included 60 patients with relapsed or refractory AML who were heavily pretreated. All of them had to have either KMT2A rearrangements or NPM1 mutations. The complete response or complete response with inadequate hematologic recovery rate with revumenib was 30%, which is about what we would expect in this population with higher-dose chemotherapy. Menin inhibitors may be kinder, and they are oral,” Dr. Sekeres said.
“Note the differentiation syndrome rate with revumenib was 16%, which is similar to what we see with IDH inhibitors in relapsed or refractory AML,” he added.
Next Ziftomenib
“Turning to ziftomenib, I found the response rates more complicated to interpret in this study because of the dose escalation involved. The bottom line is the combined complete response rate was 30%, similar to the first study. So far, these two drugs look to have comparable efficacy. Proof of concept with monotherapy is a big deal,” he stated.
“I would expect that we will see better responses as these drugs are combined in the relapsed or refractory setting and eventually upfront,” Dr. Sekeres said.
DISCLOSURE: Dr. Sekeres has served as a consultant or advisor to Bristol Myers Squibb, Celgene, Novartis, and Takeda/Millennium.
