Rory M. Shallis, MD
Rory M. Shallis, MD, Assistant Professor of Medicine (Hematology) at Yale School of Medicine, shared his thoughts on the use of revumenib in histone-lysine N-methyltransferase 2A-rearranged (KMT2A-rearranged) leukemia, as reported in the phase II AUGMENT-101 trial. In an interview with The ASCO Post, he emphasized that the emergence of menin inhibitors in KMT2A-rearranged leukemia could be a much-needed therapeutic breakthrough for a challenging subset of patients. Revumenib is but one of several menin inhibitors in development in this “emerging therapeutic space,” he added.
This class of drugs will target two disease subtypes. One is NPM1-mutated acute myeloid leukemia (AML), which accounts for about 30% of new AML cases at diagnosis. The other is AML with KMT2A rearrangements, which is seen in about 10% of adult cases of AML (and is more common in children than in adults). “Although KMT2A-rearranged leukemia is less common than NPM1-mutated leukemia, it confers a worse prognosis, mostly driven by its extraordinarily high relapse rate. Our goal is to get patients into a suitable form of remission, so they can proceed to transplant,” he said.
“To be honest, I cannot wait to use these drugs. They appear to address more than one of the greatest unmet needs in AML,” Dr. Shallis commented. He noted that about 70% of the study population had prior exposure to venetoclax. “This is critical. Currently, we have nothing that works well (if at all) after venetoclax failure,” he added. “Many would regard a median overall survival of 8 months as being underwhelming, and yes, it certainly is insufficient, but revumenib in this population represents a great step forward.”
Dr. Shallis continued: “Although AUGMENT-101 was not a front-line trial, it bolsters confidence in our effort to improve our front-line standards for KMT2A-rearranged disease, specifically by way of improving the depth of initial remission before proceeding to transplant and thus likely associating with improved outcomes. The hope would be that we could spare patients from even needing salvage therapy. These trials are underway, and we eagerly await clinical results.”
Finally, Dr. Shallis emphasized, this drug is an oral monotherapy. “Most patients in this setting are getting therapy that is burdensome, either intensive and requiring protracted admission to the hospital, or repeated intravenous or subcutaneous administration in a cyclic and indefinite fashion. An effective pill such as revumenib is an attractive option for these patients in critical need.”
DISCLOSURE: Dr. Shallis has served as a consultant to Kura Oncology.
