{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T21:29:28Z","timestamp":1794259768213,"version":"4.9.0"},"reference-count":27,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7,31]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2024027506","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T16:14:43Z","timestamp":1744733683000},"page":"601-611","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":80,"title":["The ENHANCE-3 study: venetoclax and azacitidine plus magrolimab or placebo for untreated AML unfit for intensive therapy"],"prefix":"10.1182","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7103-373X","authenticated-orcid":false,"given":"Naval","family":"Daver","sequence":"first","affiliation":[{"name":"1Department of Leukemia, MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3931-0914","authenticated-orcid":false,"given":"Paresh","family":"Vyas","sequence":"additional","affiliation":[{"name":"2MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerwin","family":"Huls","sequence":"additional","affiliation":[{"name":"3Department of Hematology, Universitair Medisch Centrum Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2116-5536","authenticated-orcid":false,"given":"Hartmut","family":"D\u00f6hner","sequence":"additional","affiliation":[{"name":"4Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1170-8683","authenticated-orcid":false,"given":"S\u00e9bastien","family":"Maury","sequence":"additional","affiliation":[{"name":"5Hematology Department, H\u00f4pitaux Universitaires Henri Mondor, Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1241-1635","authenticated-orcid":false,"given":"Jan","family":"Novak","sequence":"additional","affiliation":[{"name":"6Department of Hematology, Fakultn\u00ed Nemocnice Kr\u00e1lovsk\u00e9 Vinohrady, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8705-8333","authenticated-orcid":false,"given":"Cristina","family":"Papayannidis","sequence":"additional","affiliation":[{"name":"7IRCCS Azienda Ospedaliero Universitaria di Bologna, Istituto di Ematologia \u201cSer\u00e0gnoli,\u201d Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Mart\u00ednez Chamorro","sequence":"additional","affiliation":[{"name":"8Hematology Department, Hospital Universitario Quir\u00f3nsalud Madrid and Universidad Europea de Madrid, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3275-5593","authenticated-orcid":false,"given":"Pau","family":"Montesinos","sequence":"additional","affiliation":[{"name":"9Department of Hematology, Hospital Universitario La Fe, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabin","family":"Niroula","sequence":"additional","affiliation":[{"name":"10Division of Hematology-Oncology, Rhode Island Hospital, Providence, RI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Fenaux","sequence":"additional","affiliation":[{"name":"11Department of Hematology, H\u00f4pital Saint-Louis, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Esteve","sequence":"additional","affiliation":[{"name":"12Department of Hematology, Hospital Clinic de Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0772-869X","authenticated-orcid":false,"given":"Shang-Ju","family":"Wu","sequence":"additional","affiliation":[{"name":"13Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3727-5190","authenticated-orcid":false,"given":"Adrien","family":"De Voeght","sequence":"additional","affiliation":[{"name":"14Department of Medicine, Centre Hospitalier Universitaire de Li\u00e8ge Site Sart Tilman, Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiri","family":"Mayer","sequence":"additional","affiliation":[{"name":"15Department of Internal Medicine-Hematology and Oncology, Faculty Hospital Brno and Masaryk University, Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J. 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