Revumenib monotherapy achieved high overall response rates (ORR) and measurable residual disease (MRD) negativity rates in patients with relapsed or refractory histone-lysine N-methyltransferase 2A rearranged (KMT2Ar) acute leukemias, according to a study presented at the European Hematology Association 2024 Hybrid Congress in Madrid, Spain.
Ibrahim Aldoss, MD, and colleagues presented data from two cohorts of the pivotal phase II AUGMENT-101 trial. Cohort A included patients with KMT2Ar acute lymphoblastic leukemia (ALL) or mixed phenotype acute leukemia (MPAL), while Cohort B included patients with KMT2Ar acute myeloid leukemia (AML).
Ninety-four patients received revumenib every 12 hours with a strong cytochrome P450 3A4 inhibitor in 28-day cycles. The primary endpoints were safety, tolerability, and complete remission (CR) plus CR with partial hematologic recovery (CRh) rate (CR+CRh). Secondary endpoints included composite CR rate (CRc) and ORR.
Of the 82% of patients who experienced treatment-related adverse events (TRAEs), 51 (54%) experienced grade ≥3 TRAEs such as differentiation syndrome (16%), febrile neutropenia (14%), and prolonged heart-rate corrected QT interval (14%). A total of 6% of patients discontinued treatment due to TRAEs.
After a median follow-up of 6.1 months, the CR+CRh rate was 23% (95% CI, 12.7-35.8) and the ORR was 63% (95% CI, 49.3-75.6). The median duration of CR+CRh was 6.4 months (95% CI, 3.4-not reached). Most (70%) patients with available measurable residual disease (MRD) status who achieved CR or CRh also achieved MRD negativity.
Fourteen of 36 responders (39%) continued to hematopoietic stem cell transplantation (HSCT), while half resumed treatment after HSCT.
“[Revumenib] demonstrated clinically meaningful results in a heavily pretreated KMT2Ar population, including high ORR and MRD negativity rates and subsequent HSCT,” Dr. Aldoss and colleagues concluded. “At [interim analysis], this pivotal study met its primary endpoint, and enrollment in the KMT2Ar cohorts was stopped early for efficacy.”
Reference
Aldoss I, Issa GC, Thirman M, et al. Revumenib monotherapy in patients with relapsed/refractory kmt2ar acute leukemia: topline efficacy and safety results from the pivotal augment-101 phase 2 study. Abstract #S131. Presented at the European Hematology Association 2024 Hybrid Congress; June 13-16, 2024; Madrid, Spain.