Menin inhibition with revumenib for <i>NPM1</i>-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study

The prognosis for relapsed or refractory (R/R) nucleophosmin 1-mutated (NPM1m) acute myeloid leukemia (AML) is poor and represents an urgent unmet medical need. Revumenib, a potent, selective menin inhibitor, was recently approved for the treatment of R/R acute leukemia with a KMT2A translocation in patients aged ≥1 year based on results from the phase 1/2 AUGMENT-101 study. Here, we present results from patients with R/R NPM1m AML enrolled in the phase 2 portion of AUGMENT-101. Enrolled patients received revumenib with or without a strong CYP3A4 inhibitor every 12 hours in 28-day cycles. Primary end points were rate of complete remission (CR) or CR with partial hematologic recovery (CRh; CR + CRh), safety, and tolerability. Secondary end points included overall response rate (ORR) and duration of response. As of 18 September 2024, 84 patients received ≥1 dose of revumenib. Median age was 63 years; 1 patient was aged <18 years. The protocol-defined, efficacy-evaluable population for the primary analysis included 64 adult patients (≥3 previous lines of therapy, 35.9%; previous venetoclax, 75.0%). The CR + CRh rate was 23.4% (1-sided P = .0014); the ORR was 46.9%. Median duration of CR + CRh was 4.7 months. Of 30 responders, 5 (16.7%) proceeded to hematopoietic stem cell transplant (HSCT) and 3 resumed revumenib after HSCT. Treatment-related adverse events led to treatment discontinuation in 4 patients (4.8%). Revumenib demonstrated clinically meaningful responses in this heavily pretreated, older population with NPM1m AML, including remissions that enabled HSCT. The safety profile of revumenib was consistent with previously reported results. This trial was registered at www.clinicaltrials.gov as #NCT04065399.

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Journal
Blood
Published
2025-05-07
DOI
https://doi.org/10.1182/blood.2025028357
Citations
32
Primary Topic
Acute Myeloid Leukemia Research
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article
Field-Weighted Citation Impact
56.64

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article

Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study

Ofir Wolach, Andre C. Schuh, Arnaud Pigneux, Pau Montesinos et al.
32 citations
Blood
Acute Myeloid Leukemia Research
56.64
article

Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study

Ofir Wolach, Andre C. Schuh, Arnaud Pigneux, Pau Montesinos, Elie Traer, Maël Heiblig, Martha Arellano, Stéphane de Botton, Ashish Bajel, Ioannis Mantzaris, Michael J. Thirman, Alexander E. Perl, Ibrahim Taha Aldoss, Carolyn Grove, Cristina Papayannidis, Yakov Chudnovsky, Andrius Žučenka, Ghayas C. Issa, Irina Amitai, John F. DiPersio, John G. Harpel, Eytan M. Stein, Christine M. McMahon, Richard M. Stone, David S. Dickens, James S. Blachly, Gabriel N. Mannis, Corinna Greco, Hartmut Döhner, Yu Li, Michael W.M. Kühn, Paul J. Shami, Angela R. Smith, Emmanuel Raffoux, Tibor Kovacsovics, Rebecca G. Bagley
article en
32 citations

Abstract

The prognosis for relapsed or refractory (R/R) nucleophosmin 1-mutated (NPM1m) acute myeloid leukemia (AML) is poor and represents an urgent unmet medical need. Revumenib, a potent, selective menin inhibitor, was recently approved for the treatment of R/R acute leukemia with a KMT2A translocation in patients aged ≥1 year based on results from the phase 1/2 AUGMENT-101 study. Here, we present results from patients with R/R NPM1m AML enrolled in the phase 2 portion of AUGMENT-101. Enrolled patients received revumenib with or without a strong CYP3A4 inhibitor every 12 hours in 28-day cycles. Primary end points were rate of complete remission (CR) or CR with partial hematologic recovery (CRh; CR + CRh), safety, and tolerability. Secondary end points included overall response rate (ORR) and duration of response. As of 18 September 2024, 84 patients received ≥1 dose of revumenib. Median age was 63 years; 1 patient was aged <18 years. The protocol-defined, efficacy-evaluable population for the primary analysis included 64 adult patients (≥3 previous lines of therapy, 35.9%; previous venetoclax, 75.0%). The CR + CRh rate was 23.4% (1-sided P = .0014); the ORR was 46.9%. Median duration of CR + CRh was 4.7 months. Of 30 responders, 5 (16.7%) proceeded to hematopoietic stem cell transplant (HSCT) and 3 resumed revumenib after HSCT. Treatment-related adverse events led to treatment discontinuation in 4 patients (4.8%). Revumenib demonstrated clinically meaningful responses in this heavily pretreated, older population with NPM1m AML, including remissions that enabled HSCT. The safety profile of revumenib was consistent with previously reported results. This trial was registered at www.clinicaltrials.gov as #NCT04065399.

BloodVol. 146(9)
Albert Einstein College of Medicine (US), City Of Hope National Medical Center (US), The Royal Melbourne Hospital (AU), Memorial Sloan Kettering Cancer Center (US), Montefiore Medical Center (US), The University of Texas MD Anderson Cancer Center (US), Emory University (US), Tel Aviv University (IL), Oregon Health & Science University (US), The University of Melbourne (AU), Délégation Paris 7 (FR), Vilnius University (LT), The University of Western Australia (AU), University of Toronto (CA), Johannes Gutenberg University Mainz (DE), Washington University in St. Louis (US), Université Paris Cité (FR), University of Utah (US), Sheba Medical Center (IL), Rabin Medical Center (IL), Peter MacCallum Cancer Centre (AU), Huntsman Cancer Institute (US), Institut Gustave Roussy (FR), Sir Charles Gairdner Hospital (AU), Princess Margaret Cancer Centre (CA), Centre Hospitalier Universitaire de Bordeaux (FR), Hospital Universitari i Politècnic La Fe (ES), California University of Pennsylvania (US), University of Chicago (US), Kala Pharmaceuticals (United States) (US), University Medical Center of the Johannes Gutenberg University Mainz (DE), University of Iowa Stead Family Children’s Hospital (US), Phoenix (United States) (US), Helicon Foundation (US), City of Hope (US), Hôpital Lyon Sud (FR), Dana-Farber Cancer Institute (US), Istituto di Ematologia di Bologna (IT), Azienda USL di Bologna (IT), Stanford Medicine (US), Ospedale San Bortolo (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), University Hospital Ulm (DE), Synta Pharmaceuticals (United States) (US), Pathwest Laboratory Medicine (AU), Montefiore Einstein Comprehensive Cancer Center, The Ohio State University (US), University of Pennsylvania (US), University of Colorado Denver (US), Stanford University (US)
Amgen, Bristol-Myers Squibb, Pfizer, AstraZeneca, GlaxoSmithKline, Sanofi, Gilead Sciences, Alexion Pharmaceuticals, Celgene, American Society of Pediatric Hematology/Oncology, Jazz Pharmaceuticals, Astex Pharmaceuticals, Foghorn Therapeutics, Agios Pharmaceuticals, Incyte, Syndax Pharmaceuticals, MacroGenics, Y-mAbs Therapeutics, Astellas Pharma, Servier, Swedish Orphan Biovitrum, Genentech, Kite Pharma, Daiichi Sankyo Europe
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