Revumenib May Have Benefits for Patients with R/R KMT2Ar Acute Leukemia

Revumenib, an oral treatment, may be a beneficial option for certain patients with acute leukemia.

For patients with relapsed/refractory acute leukemia with KMT2A rearrangements (KMT2Ar), prognoses are poor, with researchers reporting that less than 10% of adult patients achieve remission with current therapies.

Most patients now receive conventional chemotherapy or Venclexta (venetoclax) combinations, with an allogeneic hematopoietic stem cell transplantation (HSCT) in consolidation, researchers noted.

However, according to study results published in the Journal of Clinical Oncology, some patients may benefit from treatment with the menin inhibitor revumenib.

Researchers noted that rearrangements of the KMT2A gene occur in up to 10% of acute leukemias and that the protein menin plays a crucial role in the development of KMT2Ar leukemia. Revumenib is an oral medication designed to inhibit the menin-KMT2A interaction.

Ninety-four patients with a median age of 37 were enrolled and treated in the study between Oct. 1, 2021 and July 24, 2023, with research reporting that among the efficacy-evaluable population of 57 patients the complete remission (CR) or CR with partial

hematologic recovery (CR plus CRh) rate was 22.8%, while the overall response rate (ORR; patients who responded partially or completely to treatment), was 63.2%, with 15 of 22 patients having no detectable residual disease.

Complete remission is the disappearance of cancer. Complete remission with partial hematologic recovery, according to The University of Texas MD Anderson Cancer Center, is similar to a CR but neutrophil count (a type of white blood cell) above 500 but below 1,000 is required for a full CR, as well as a platelet count above 50,000 but below 100,000 needed for a full CR.

The median time until the first overall response was 0.95 months, and the median time until CR plus CRh was 6.4 months, while researchers stated that at a median follow-up time of 6.1 months, the overall survival (time patients live, regardless of disease status) was 8 months.

The study population included 71 adults with a median age of 44 years, and 23 children with a median age of 4 years, with 43.6% of patients having received at least three prior lines of therapy.

Nearly all patients (93 patients, or 98.9%), experienced treatment-emergent side effects, with the most common being nausea (44.7%), febrile neutropenia (when a patient with neutropenia, a low count of neutrophils, has a fever, 38.3%) and diarrhea (35.1%). Eighty-six, or 91.5% of patients, experienced side effects of grade 3 (severe) or higher, with the most common being febrile neutropenia (37.2%), neutropenia (28.7%) and thrombocytopenia (a low count of platelets, 21.3%). Treatment-emergent side effects led to dose reduction or discontinuation among 9.6% and 12.8% of patients, respectively.

Researchers reported side effects causing death among 14 of 94 patients while receiving revumenib or within 30 days of receiving the last dose, with one case each of intracranial hemorrhage, myocardial ischemia (reduced blood flow to the heart), pneumonia and respiratory failure deemed as being possibly related to revumenib.

“In conclusion, treatment with the menin inhibitor revumenib provided clinical benefit and a low rate of discontinuation for [adverse events] indicating a predictable safety profile,” researchers wrote. “This benefit is demonstrated in refractory patients where currently available therapies are used with a palliative intent, whereas nearly a quarter of patients with resistant leukemia receiving revumenib on this study proceeded to a potentially curative HSCT.”

The study, researchers noted, is ongoing regarding its evaluation of patients with NPM1-mutated acute myeloid leukemia.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.