Revumenib Yields High Remission Rates for Acute Leukemia

Phase 1/2 AUGMENT-101 study results revealed quick and lasting responses for patients with relapsed/refractory KMT2Ar acute leukemia.

Increased efficacy and tolerable safety were observed with revumenib in patients with relapsed/refractory KMT2A-rearranged acute myeloid leukemia and acute lymphoid leukemia, according to findings from the phase 1/2 AUGMENT-101 study (NCT04065399) published in The Journal of Clinical Oncology.1

Results from the trial show that the complete remission and complete remission with partial hematological recovery (CR + CRh) rate was 22.8% (95% CI, 12.7%-35.8%) in the efficacy analysis, exceeding the 10% null hypothesis (P = .0036). Of note, the overall response rate was 63.2% (95% CI, 49.3%-75.6%), with 68.2% of patients having no detectable residual disease.

Any-grade or grade 3 or greater adverse events (AEs) occurred in 98.9% and 91.5% of patients, including grade 3 or higher febrile neutropenia (37.2%), thrombocytopenia (21.3%), and anemia (18.1%).

The AUGMENT-101 trial was the largest evaluation of targeted therapy for patients with relapsed/refractory KMT2Ar acute leukemia, according to investigators.

“Relapsed/refractory KMT2Ar acute leukemia has a poor prognosis, with 10% or less of patients achieving remission with currently available therapy. In this phase 2 study, the oral menin inhibitor revumenib led to substantially greater rates of remission compared with historical controls in patients with high-risk, relapsed/refractory KMT2Ar acute leukemia,” wrote Ghayas C. Issa, MD, medical oncologist in the Department of Leukemia and Genomic Medicine at The University of Texas MD Anderson Cancer Center, with study coinvestigators in the publication.

“The prespecified primary study end point was met, with a rate of CR + CRh of 22.8%. Although sample sizes were small, efficacy was observed across subgroups, including age, lineage, prior venetoclax [Venclexta], and KMT2A translocation partner,” he continued.

The phase 1/2, open-label, dose-escalation and expansion study enrolled patients 30 days or older with primary refractory or relapsed/refractory KMT2Ar acute leukemia of any lineage (n = 94). Results for the phase 2 trial were reported from October 1, 2021, to July 24, 2023.

The median patient age in the efficacy population was 34.0 years, with 64.9% being aged 18 to 64. A total of 57.9% were female and 75.4% were White. Of note, 86.0% had AML, 12.3% had ALL, and 1.8% had acute leukemia of ambiguous lineage.

Of patients evaluable for efficacy (n = 57), median time to first overall response was 0.95 months (range, 0.9-2.0), with a median time to CR + CRh of 1.9 months (range, 0.9-4.6). With a median follow-up of CR + CRh was 6.1 months (range, 0.3-18.6), and the median CR + CRh duration was 6.4 months (95% CI, 3.4 to not reached [NR]). The median overall survival (OS) was 8.0 months (95% CI, 4.1-10.9)

Revumenib was orally administered to patients every 12 hours in 28-day continuous cycles with adjusted doses for patients weighing less than 40 kg based on body surface area. Dosage varied depending on the use of a strong CYP3A4 inhibitor; 163 mg or 95 mg/m2 if less than 40 kg once every 12 hours when used with a strong CYP3A4. Alternatively, the dosage was 276 mg or 160 mg/m2 if less than 40 kg once every 12 hours without. Treatment continued until lack of response after up to 4 cycles, unacceptable AEs, disease progression, or withdrawal of consent.

The coprimary end points of the study were CR or CR + CRh and the safety and tolerability of revumenib. Secondary end points include ORR, duration of remission, and overall OS.

Of the patients evaluable for safety (n = 94), treatment-emergent AEs leading to dose interruption, reduction, or discontinuation occurred in 43.6%, 9.6%, and 12.8% of patients. A total of 14.9% of patients died receiving revumenib or within 30 days of last dose. The median duration of treatment was 10.0 weeks (range, 1-36).

Reference

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