Abstract
AML-110: Patients With Relapsed or Refractory (R/R) Nucleophosmin 1–Mutated (NPM1m) Acute Myeloid Leukemia (AML): Updated Results From the Revumenib Phase 2 AUGMENT-101 Study
Clinical lymphoma, myeloma and leukemia, Vol.25(Suppl 1), pp.S400-S400
09/2025
DOI: 10.1016/S2152-2650(25)01622-2
Abstract
The prognosis for patients with R/R NPM1m AML is poor. The menin-KMT2A interaction is a critical driver of leukemogenesis in NPM1m AML. Revumenib, a first-in-class, potent, selective menin inhibitor that disrupts menin-KMT2A interactions, demonstrated activity in patients with R/R NPM1m AML in AUGMENT-101 phase 1 (NCT04065399).
Present phase 2 results in patients with R/R NPM1m AML in AUGMENT-101.
Aged ≥30 days with R/R NPM1m AML (patient/caregiver consent).
Revumenib 160 mg q12h + strong CYP3A4 inhibitor given in 28-day cycles until unacceptable toxicity, disease progression, or lack of response after ≤4 cycles.
Safety, tolerability, and rate of CR +CRh in efficacy population (defined as centrally confirmed NPM1 mutation, ≥5% bone marrow blasts at baseline within 28 days prior to study start, and ≥6 months of treatment). MRD testing was conducted locally by PCR or flow cytometry (investigator's discretion).
As of September 18, 2024, 84 patients received ≥1 dose of revumenib (safety population). The median age was 63 (range: 11–84) years, with one patient <18 years. Treatment history: 34.5% had ≥3 prior lines of therapy and 73.8% had received prior venetoclax. Efficacy population: CR+CRh rate was 26.0% (20/77; 95% CI, 16.6%–37.2%). The median duration of CR+CRh was 4.7 (95% CI, 2.1–8.2) months. Median time to first response was 2.76 (range: 0.9–8.8) months. Twelve of 19 MRD-evaluable CR+CRh responders (63.2%) were MRD negative (PCR, n = 6; flow, n = 6) after a median time of 2.78 (range: 1.8–4.7) months. Five patients proceeded to HSCT. Safety population: 66 patients (78.6%) experienced a treatment-related AE (TRAE); 50 (59.5%) experienced a grade ≥3 TRAE. The most common grade ≥3 TRAEs were QTc prolongation (18 [21.4%]), anemia (12 [14.3%]), febrile neutropenia (11 [13.1%]), and differentiation syndrome (11 [13.1%]; grade 3, 9 [10.7%]; grade 4, 2 [2.4%]). TRAEs led to treatment discontinuation in four (4.8%) patients and death of one (1.2%) patient.
Revumenib continues to demonstrate clinically meaningful responses and manageable safety outcomes in this heavily pretreated, older population with R/R NPM1mAML. These findings support further investigation of revumenib in earlier lines of therapy and in combination. Sponsorship: Syndax Pharmaceuticals.
Details
- Title: Subtitle
- AML-110: Patients With Relapsed or Refractory (R/R) Nucleophosmin 1–Mutated (NPM1m) Acute Myeloid Leukemia (AML): Updated Results From the Revumenib Phase 2 AUGMENT-101 Study
- Creators
- Martha L. Arellano - Winship Cancer InstituteMichael J. Thirman - University of ChicagoJohn F. DiPersio - Washington University in St. Louis School of MedicineMaël Heiblig - Hôpital Lyon SudEytan M. Stein - Memorial Sloan Kettering Cancer CenterAndre C. Schuh - University of TorontoAndrius Žucenka - Vilnius UniversityStéphane De Botton - Institut Gustave RoussyCarolyn S. Grove - Sir Charles Gairdner HospitalGabriel N. Mannis - Stanford University School of MedicineCristina Papayannidis - IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'OrsolaAlexander E. Perl - University of PennsylvaniaGhayas C. Issa - The University of Texas MD Anderson Cancer CenterIbrahim Aldoss - City Of Hope National Medical CenterAshish Bajel - The University of MelbourneDavid S. Dickens - University of IowaMichael W.M. Kühn - University Medical Center of the Johannes Gutenberg University MainzIoannis Mantzaris - Montefiore Einstein Comprehensive Cancer CenterEmmanuel Raffoux - Université Paris CitéElie Traer - OHSU Knight Cancer InstituteIrina Amitai - Sheba Medical CenterHartmut Döhner - University Hospital UlmCorinna Greco - Ospedale San BortoloTibor Kovacsovics - City Of Hope National Medical CenterChristine M. McMahon - University of Colorado Anschutz Medical CampusPau Montesinos - Hospital Universitari i Politècnic La FeArnaud Pigneux - Centre Hospitalier Universitaire de BordeauxPaul J. Shami - University of UtahRichard M. Stone - Dana-Farber Cancer InstituteOfir Wolach - Tel Aviv UniversityJohn G. Harpel - ICON plc, Blue Bell, PA, USAYakov Chudnovsky - Syndax Pharmaceuticals, Inc., New York, NY, USALi Yu - Syndax Pharmaceuticals, Inc., New York, NY, USARebecca G. Bagley - Syndax Pharmaceuticals, Inc., New York, NY, USAAngela R. Smith - Syndax Pharmaceuticals, Inc., New York, NY, USAJames S. Blachly - The Ohio State University
- Resource Type
- Abstract
- Publication Details
- Clinical lymphoma, myeloma and leukemia, Vol.25(Suppl 1), pp.S400-S400
- DOI
- 10.1016/S2152-2650(25)01622-2
- ISSN
- 2152-2650
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 09/2025
- Academic Unit
- Stead Family Department of Pediatrics; Hematology/Oncology
- Record Identifier
- 9984949231602771
Metrics
5 Record Views