The ENHANCE-3 study: venetoclax and azacitidine plus magrolimab or placebo for untreated AML unfit for intensive therapy

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.

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Journal
Blood
Published
2025-04-15
DOI
https://doi.org/10.1182/blood.2024027506
Citations
33
Primary Topic
Neutropenia and Cancer Infections
Type
article
Field-Weighted Citation Impact
34.50

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article

The ENHANCE-3 study: venetoclax and azacitidine plus magrolimab or placebo for untreated AML unfit for intensive therapy

Guru Subramanian Guru Murthy, Carmen Martínez Chamorro, Pau Montesinos, Sébastien Maury et al.
33 citations
Blood
Neutropenia and Cancer Infections
34.50
article

The ENHANCE-3 study: venetoclax and azacitidine plus magrolimab or placebo for untreated AML unfit for intensive therapy

Guru Subramanian Guru Murthy, Carmen Martínez Chamorro, Pau Montesinos, Sébastien Maury, Shang‐Ju Wu, Pierre Fenaux, Jordi Esteve, Adrien De Voeght, Naval Guastad Daver, Cristina Papayannidis, Rabin Niroula, Sowmya B. Kuwahara, Jiřı́ Mayer, Lisa D. Johnson, Jan Novák, Peter J.M. Valk, Paresh Vyas, Hartmut Döhner, Kenneth J. Caldwell, Ke Liu, Gerwin A. Huls, Mei Dong
article en
33 citations

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.

BloodVol. 146(5)
Froedtert Hospital (US), University Medical Center Groningen (NL), The University of Texas MD Anderson Cancer Center (US), Medical College of Wisconsin (US), Masaryk University (CZ), Brown University (US), Rhode Island Hospital (US), Erasmus MC (NL), Hospital Universitari i Politècnic La Fe (ES), University of Oxford (GB), University Hospital Brno (CZ), Dialyse Centrum Groningen (NL), Hospital Universitario Quirónsalud Madrid (ES), MRC Weatherall Institute of Molecular Medicine (GB), Hospital Clínic de Barcelona (ES), Istituto di Ematologia di Bologna (IT), Azienda USL di Bologna (IT), Gilead Sciences (Spain) (ES), Hôpitaux Universitaires Henri-Mondor (FR), National Taiwan University Hospital (TW), Centre Hospitalier Universitaire de Liège (BE), Gilead Sciences (United States) (US), Hôpital Saint-Louis (FR), Erasmus MC Cancer Institute (NL), University Hospital Ulm (DE), University Hospital Kralovske Vinohrady (CZ)
AstraZeneca, Gilead Sciences, BeiGene, Astellas Pharma, Servier
Good health and well-being
Openalex Percentile: Top 0%
Neutropenia and Cancer Infections
34.50
DOIOpen Access PDFOpenAlex
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