FDA Approves Revumenib in KMT2A-Rearranged Acute Leukemia
Revumenib is now an FDA-approved treatment for adult and pediatric patients with relapsed/refractory KMT2A-rearranged acute leukemia.
A close-up of red blood cells flowing through a vein: © catalin - stock.adobe.com
- Revumenib (SNDX-5613) is now an approved treatment by the FDA for patients with relapsed/refractory KMT2A-rearranged acute leukemia.
- The Menin inhibitor is the first drug indicated to treat patients with KMT2A-rearranged acute leukemia.
- Findings from the AUGMENT-101 trial (NCT04065399) support this regulatory decision.
The FDA has granted approval to revumenib for the treatment of adult and pediatric patients with relapsed/refractory KMT2A-rearranged acute leukemia.1
Data from the phase 1/2 AUGMENT-101 trial, as well as the additional information provided to the FDA, support this approval. In AUGMENT-101, revumenib led to complete remissions (CRs) with a CR with partial hematologic recovery (CRh) rate of 21.2% (95% CI, 13.8%-30.3%) among adult and pediatric patients with relapsed/refractory acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) harboring KMT2A rearrangements, meeting the study’s primary end point.2,3 The median CR with CRh duration was 6.4 months (95% CI, 2.7-not estimable)
These findings were from 57 adult and pediatric patients with KMT2A-rearranged AML or ALL who were treated with revumenib alone. The median time to CR/CRh was 1.9 months (95% CI, 0.9-4.5).
“The approval of revumenib is a major addition to our armamentarium of treatments for patients with KMT2A-rearranged acute leukemias. KMT2A-rearrangements occur in patients with acute myeloid and acute lymphoblastic leukemia, in adults and children and overall, have a poor prognosis. Revumenib gives hope to those with relapsed and refractory KMT2Ar disease. I hope to see this agent investigated in clinical trials for newly diagnosed KMT2Ar AML and ALL,” Eytan M. Stein, MD, chief of the leukemia service and director of the Program for Drug Development in Leukemia, Division of Hematologic Malignancies, at Memorial Sloan Kettering Cancer Center in New York, New York, told Targeted OncologyTM.
A total of 94 patients were evaluated in the AUGMENT-101 study from October 1, 2021, to July 24, 2023, and 57 patients were evaluable for efficacy.2 Along with meeting the primary end point of CR/CRh rate, among the adult patients, the CR and CRh rate was 23% (10/44; 95% CI, 11.5%-37.8%) and 23% in pediatric patients (3/13; 95% CI, 5.0%-53.8%).
The overall response rate was 63% (95% CI, 49.3%-75.6%) in the overall cohort, and the median overall survival at the data cutoff was 8.0 months (95% CI, 4.1-10.9). Responses were durable with a median duration of 6.4 months (95% CI, 3.4-not reached). Additionally, 46% (6/13) of patients remained in response at the time of data cutoff.
Minimal residual disease (MRD) was evaluated in 10 patients who had a CR/CRh, 70% of whom were MRD-negative. A total of 68% of the evaluable patients with a composite CR (n = 22) were MRD-negative.
Looking at safety, any-grade treatment-related adverse events observed in over 20% of patients included nausea (28%), differentiation syndrome (27%), and QTc prolongation (23%). Grade 3 differentiation syndrome was observed in 15% of patients, and 1 patient had grade 4 differentiation syndrome. Grade 3 QTc prolongation was observed in 14% of patients; however, no grade 4 or 5 events were observed. Further, no patients stopped treatment due to differentiation syndrome, QTc prolongation, or cytopenias.
REFERENCES:
1. FDA approves revumenib for relapsed or refractory acute leukemia with a KMT2A translocation. News release. FDA. November 15, 2024. Accessed November 15, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-revumenib-relapsed-or-refractory-acute-leukemia-kmt2a-translocation?utm_medium=email&utm_source=govdelivery
2. Issa GC, Aldoss I, Thirman MJ, et al. Menin inhibition with revumenib for KMT2A-rearranged relapsed or refractory acute leukemia (AUGMENT-101). J Clin Oncol. Published online August 9, 2024. doi:10.1200/JCO.24.00826
3. Syndax presents positive data from pivotal AUGMENT-101 trial of revumenib in relapsed/refractory KMT2Ar acute leukemia at late-breaking oral presentation during 65th ASH Annual Meeting. News release. Syndax. December 12, 2023. Accessed August 16, 2024. https://tinyurl.com/2p3yzrez
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