Fludarabine, Cytarabine, Granulocyte Colony-Stimulating Factor, and Idarubicin With Gemtuzumab Ozogamicin Improves Event-Free Survival in Younger Patients With Newly Diagnosed AML and Overall Survival in Patients With NPM1 and FLT3 Mutations.

Autor:	Russell NH; Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom., Wilhelm-Benartzi C; Centre for Trials Research, Cardiff University, Cardiff, United Kindgom., Othman J; Department of Medical and Molecular Genetics, Kings College London, London, United Kingdom., Dillon R; Department of Medical and Molecular Genetics, Kings College London, London, United Kingdom., Knapper S; School of Medicine, Cardiff University, Cardiff, United Kingdom., Batten LM; Centre for Trials Research, Cardiff University, Cardiff, United Kindgom., Canham J; Centre for Trials Research, Cardiff University, Cardiff, United Kindgom., Hinson EL; Centre for Trials Research, Cardiff University, Cardiff, United Kindgom., Betteridge S; Centre for Trials Research, Cardiff University, Cardiff, United Kindgom., Overgaard UM; Copenhagen University Hospital, Copenhagen, Denmark., Gilkes A; School of Medicine, Cardiff University, Cardiff, United Kingdom., Potter N; Department of Medical and Molecular Genetics, Kings College London, London, United Kingdom., Mehta P; University Hospitals of Bristol and Weston NHS Trust, Bristol, United Kingdom., Kottaridis P; University College London Hospitals NHS Foundation Trust, London, United Kingdom., Cavenagh J; Department of Haematology, St Bartholomew's Hospital, London, United Kingdom., Hemmaway C; Auckland Hospital, Auckland, New Zealand., Arnold C; Belfast City Hospital, Belfast, United Kingdom., Freeman SD; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom., Dennis M; The Christie NHS Foundation Trust, Manchester, United Kingdom.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2024 Apr 01; Vol. 42 (10), pp. 1158-1168. Date of Electronic Publication: 2024 Jan 12.
DOI:	10.1200/JCO.23.00943
Abstrakt:	Purpose: To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods: One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results: There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 ( P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion: Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit.
Databáze:	MEDLINE
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