The ENHANCE-3 study: venetoclax and azacitidine plus magrolimab or placebo for untreated AML unfit for intensive therapy
Abstract
Abstract Patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy (IC) have limited treatment options. The phase 3 ENHANCE-3 study aimed to determine whether magrolimab (magrolimab arm) was superior to placebo (control arm) when either was combined with venetoclax and azacitidine. Adults with previously untreated AML who were ineligible for IC were randomized to receive magrolimab (1 mg/kg on days 1 and 4, 15 mg/kg on day 8, 30 mg/kg on days 11 and 15, then weekly for 5 weeks, and then every 2 weeks) or placebo, venetoclax (100 mg on day 1, 200 mg on day 2, and 400 mg daily thereafter), and azacitidine (75 mg/m2 days 1-7) in 28-day cycles. The primary end point was overall survival (OS); key secondary end points included complete remission (CR) rate and safety. After randomization of 378 patients, the trial was stopped at a prespecified interim analysis owing to futility. At final analysis, with median follow-up of 7.6 months (magrolimab arm) vs 7.4 months (control arm), median OS was 10.7 vs 14.1 months (hazard ratio, 1.178; 95% confidence interval, 0.848-1.637). The CR rate within 6 cycles was 41.3% vs 46.0%. Addition of magrolimab to venetoclax and azacitidine resulted in more fatal adverse events (19.0% vs 11.4%), primarily driven by grade 5 infections (11.1% vs 6.5%) and respiratory events (2.6% vs 0%). There were similar incidences of any-grade infections, febrile neutropenia, and neutropenia between arms. These results highlight the difficulty in improving outcomes for patients with AML who were ineligible for IC. This trial was registered at www.clinicaltrials.gov as #NCT05079230.
Article Details
Authors (22)
Naval Daver
1The University of Texas MD Anderson Cancer Center, Houston, TX
Paresh Vyas
Gerwin Huls
3Department of Hematology, Universitair Medisch Centrum Groningen, Groningen, The Netherlands
Hartmut Döhner
1Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
Sébastien Maury
12Service d’Hématologie Clinique, Hôpital Henri-Mondor, Assistance Publique-Hôpitaux de Paris, Paris, France
Jan Novak
Cristina Papayannidis
2IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Bologna, Italy
Carmen Martinez Chamorro
Hospital Universitario Quironsalud Madrid and Universidad Europea de Madrid, Pozuelo de Alarcon, Spain
Pau Montesinos
Hospital Universitari i Politecnic La Fe, Valencia, Spain
Rabin Niroula
2Rhode Island Hospital, Division of Hematology-Oncology, Department of Medicine, Providence, United States
Pierre Fenaux
Jordi Esteve
13Hematology Department, Institute of Cancer & Blood Diseases (ICAMS), Hospital Clinic, Barcelona, Spain
Shang-Ju Wu
Adrien De Voeght
1University Of Liège, Montefiore Institute, Department of Electrical Engineering and Computer Science, Artificial Intelligence and Deep Learning, Liège, Belgium
Jiri Mayer
6Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Masaryk University Brno, Brno, Czech Republic
Peter J. M. Valk
2Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
Lisa Johnson
17Gilead Sciences, Inc, Foster City, CA
Mei Dong
State Key Laboratory of Coal Conversion
Ke Liu
Sowmya Kuwahara
17Gilead Sciences, Inc, Foster City, CA
Kenneth Caldwell
17Gilead Sciences, Inc, Foster City, CA
Guru Subramanian Guru Murthy
Medical College of Wisconsin, Milwaukee, Wisconsin, United States