Dr Stahl on Key Genetic Tests for Menin Inhibitor Use in AML

“Both [RNA-based testing and next-generation sequencing] are important to do if we want to get more patients who are potentially eligible for a menin inhibitor to receive [revumenib].”

Maximilian Stahl, MD, physician, Medical Oncology, Dana-Farber Cancer Institute; instructor in medicine, Harvard Medical School, discusses key considerations when determining a patient’s eligibility for targeted therapies like revumenib (Revuforj) in acute myeloid leukemia (AML), particularly with respect to RNA vs DNA testing for KMT2Arearrangements and other markers.

Comprehensive genetic testing plays a critical role in identifying patients who may benefit from targeted therapies, Stahl begins. This is increasingly recognized in the field of AML, where waiting for genetic testing results before finalizing treatment decisions is becoming a standard approach, he explains. When considering the use of menin inhibitors for a patient with AML, testing for KMT2A rearrangements is essential, Stahl emphasizes. Although some of these rearrangements can be identified through standard cytogenetic analysis, others may not be readily detectable with conventional methods, Stahl says, adding that the use of advanced techniques to identify these rearrangements is therefore crucial. 

One such method involves RNA-based testing, he continues, which can detect multiple fusions through a technique known as reverse transcription polymerase chain reaction. This approach ensures that KMT2A rearrangements are not overlooked, thereby identifying patients who may benefit from menin inhibitor therapy, Stahl states. He notes that without such thorough testing, eligible patients may be missed. 

In contrast, the NPM1 mutation, which is another relevant target in AML, can typically be detected with standard next-generation sequencing, he continues. This method complements RNA-based testing and ensures a comprehensive evaluation of genetic alterations. Ultimately, incorporating sophisticated genetic testing techniques into standard practice is essential for optimizing patient outcomes in AML and expanding the pool of patients who can access menin inhibitors, Stahl concludes.