The ENHANCE-3 study: venetoclax and azacitidine plus magrolimab or placebo for untreated AML unfit for intensive therapy
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu časopisecké články, randomizované kontrolované studie, klinické zkoušky, fáze III, multicentrická studie
PubMed
40233321
PubMed Central
PMC12824654
DOI
10.1182/blood.2024027506
PII: 536723
Knihovny.cz E-zdroje
- MeSH
- akutní myeloidní leukemie * farmakoterapie mortalita MeSH
- azacytidin * aplikace a dávkování škodlivé účinky MeSH
- bicyklické sloučeniny heterocyklické aplikace a dávkování škodlivé účinky MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- humanizované monoklonální protilátky * aplikace a dávkování škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- protokoly protinádorové kombinované chemoterapie * terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sulfonamidy aplikace a dávkování škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- azacytidin * MeSH
- bicyklické sloučeniny heterocyklické MeSH
- humanizované monoklonální protilátky * MeSH
- sulfonamidy MeSH
- venetoclax MeSH Prohlížeč
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.
Department of Hematology Erasmus MC Cancer Institute Rotterdam The Netherlands
Department of Hematology Fakultní Nemocnice Královské Vinohrady Prague Czech Republic
Department of Hematology Hôpital Saint Louis Paris France
Department of Hematology Hospital Clinic de Barcelona Barcelona Spain
Department of Hematology Hospital Universitario La Fe Valencia Spain
Department of Hematology Universitair Medisch Centrum Groningen Groningen The Netherlands
Department of Internal Medicine 3 Ulm University Hospital Ulm Germany
Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan
Department of Leukemia MD Anderson Cancer Center Houston TX
Department of Medicine Centre Hospitalier Universitaire de Liège Site Sart Tilman Liège Belgium
Division of Hematology and Oncology Froedtert and Medical College of Wisconsin Milwaukee WI
Division of Hematology Oncology Rhode Island Hospital Providence RI
Gilead Sciences Inc Foster City CA
Hematology Department Hôpitaux Universitaires Henri Mondor Créteil France
IRCCS Azienda Ospedaliero Universitaria di Bologna Istituto di Ematologia Seràgnoli Bologna Italy
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ClinicalTrials.gov
NCT05079230
