Menin inhibition with revumenib for <i>NPM1</i>-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study
Abstract
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 &lt;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.
Article Details
Authors (36)
Martha L. Arellano
1Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University School of Medicine, Atlanta, GA
Michael J. Thirman
2Department of Medicine, Section of Hematology and Oncology, The University of Chicago Medicine, Chicago, IL
John F. DiPersio
Department of Medicine, Washington University School of Medicine, St. Louis
Maël Heiblig
9Department of Hematology, Centre Hospitalier Universitaire de Lyon, Lyon, France
Eytan M. Stein
Leukemia Service Department of Medicine Memorial Sloan Kettering Cancer Center New York New York USA
Andre C. Schuh
6Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre and University of Toronto, Toronto, ON, Canada
Andrius Zucenka
1Vilnius University, Faculty of Medicine and Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania
Stéphane de Botton
Carolyn S. Grove
9Department of Haematology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
Gabriel N. Mannis
Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA
Cristina Papayannidis
2IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Bologna, Italy
Alexander E. Perl
Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Ghayas C. Issa
Ibrahim Aldoss
Ashish Bajel
5Peter MacCallum Cancer Centre and The Royal Melbourne Hospital, University of Melbourne, Department of Clinical Haematology, Melbourne, Australia
David S. Dickens
19Division of Pediatric Hematology/Oncology, University of Iowa Stead Family Children’s Hospital, Iowa City, IA
Michael W. M. Kühn
1Department of Hematology and Oncology, Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
Ioannis Mantzaris
1Montefiore Medical Center, Bronx, United States
Emmanuel Raffoux
Elie Traer
Oregon Health & Science University, Portland, Oregon, United States
Irina Amitai
1Tel Aviv University, Sackler Faculty Of Medicine, Tel Aviv, Israel
Hartmut Döhner
1Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
Corinna Greco
24Ospedale San Bortolo, Vicenza, Italy
Tibor Kovacsovics
9City of Hope, Goodyear, United States
Christine M. McMahon
University of Colorado, Aurora, Colorado, United States
Pau Montesinos
Hospital Universitari i Politecnic La Fe, Valencia, Spain
Arnaud Pigneux
Paul J. Shami
32Division of Hematology and Hematologic Malignancies, University of Utah Huntsman Cancer Institute, Salt Lake City, UT
Richard M. Stone
8Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
Ofir Wolach
1Tel Aviv University, Sackler Faculty Of Medicine, Tel Aviv, Israel
John G. Harpel
35ICON plc, New York, NY
Yakov Chudnovsky
34Syndax Pharmaceuticals, Inc., New York, United States
Li Yu
Rebecca G. Bagley
36Syndax Pharmaceuticals, Inc, Waltham, MA
Angela R. Smith
34Syndax Pharmaceuticals, Inc., New York, United States
James S. Blachly
10Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH