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Acute Myeloid Leukemia
Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial
Ferrata Storti Foundation
Haematologica 2019 Volume 104(1):113-119
Juliette Lambert,1 Cécile Pautas,2 Christine Terré,3 Emmanuel Raffoux,4 Pascal Turlure,5 Denis Caillot,6 Ollivier Legrand,7 Xavier Thomas,8 Claude Gardin,9 Karïn Gogat-Marchant,10 Stephen D. Rubin,11
Rebecca J. Benner,12 Pierre Bousset,13 Claude Preudhomme,14
Sylvie Chevret,15 Herve Dombret16 and Sylvie Castaigne17
1Service d'Hématologie et Oncologie, Centre Hospitalier de Versailles, Le Chesnay, France; 2Service d’Hématologie et de Thérapie Cellulaire, Hôpital Henri Mondor, Créteil, France; 3Laboratoire de Cytogénétique, Centre Hospitalier de Versailles, France; 4Hôpital Saint-Louis (AP-HP), Université Paris Diderot, France; 5Service d'Hématologie Clinique et Thérapie Cellulaire, Centre Hospitalier Universitaire, Limoges, France; 6Hematologie Clinique, Hôpital François Mitterrand, Centre Hospitalier Universitaire, Dijon, France; 7Hôpital Saint-Antoine (AP-HP), Université Paris Pierre et Marie Curie, France; 8Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Université Lyon 1, Pierre Benite, France; 9Hôpital Avicenne (AP-HP), Université Paris 13, Bobigny, France; 10Global Clinical Development Pfizer Inc., Paris, France; 11Global Product Development, Pfizer Inc., Collegeville, PA, USA; 12Global Product Development, Pfizer Inc., Groton, CT, USA; 13Pfizer Oncology, Pfizer Inc., Paris, France; 14Université Lille, INSERM, Centre Hospitalier Universitaire Lille, UMR-S 1172 - Jean-Pierre Aubert Center - Centre de Recherche, Lille, France; 15Departement de Biostatistique, Hôpital Saint-Louis (AP-HP), Universite Paris Diderot, INSERM S 717, France; 16Hopital Saint-Louis (AP-HP), Universite Paris Diderot, France and 17Service d'Hématologie et Oncologie, Centre Hospitalier de Versailles, Université de Versailles Saint Quentin, Le Chesnay, France
ABSTRACT
The randomized, phase III ALFA-0701 trial showed that a reduced and fractionated dose of gemtuzumab ozogamicin added to stan- dard front-line chemotherapy significantly improves event-free survival (EFS) in adults with de novo acute myeloid leukemia (AML). Here we report an independent review of EFS, final overall survival (OS), and additional safety results from ALFA-0701. Patients (n=271) aged 50-70 years with de novo AML were randomized to receive conventional front- line induction chemotherapy (3+7 daunorubicin+cytarabine) with/with- out gemtuzumab ozogamicin 3 mg/m2 on days 1, 4, and 7 during induc- tion. Patients in remission following induction therapy received 2 cours- es of consolidation therapy (daunorubicin+cytarabine) with/without gemtuzumab ozogamicin (3 mg/m2/day on day 1) according to their ini- tial randomization. The primary end point was investigator-assessed EFS. Secondary end points included OS and safety. A blinded independ- ent review confirmed the investigator-assessed EFS results [August 1, 2011; hazard ratio (HR) 0.66; 95% Confidence Interval (CI): 0.49-0.89; 2- sided P=0.006], corresponding to a 34% reduction in risk of events in the gemtuzumab ozogamicin versus control arm. Final OS at April 30, 2013 favored gemtuzumab ozogamicin but was not significant. No differ- ences in early death rate were observed between arms. The main toxic- ity associated with gemtuzumab ozogamicin was prolonged thrombo- cytopenia. Veno-occlusive disease (including after transplant) was observed in 6 patients in the gemtuzumab ozogamicin arm and 2 in the control arm. In conclusion, gemtuzumab ozogamicin added to standard intensive chemotherapy has a favorable benefit/risk ratio. These results expand front-line treatment options for adult patients with previously untreated AML. (Trial registered at clinicaltrials.gov;identifier: 00927498.)
Correspondence:
scastaigne@ch-versailles.fr
Received: January 17, 2018. Accepted: July 25, 2018. Pre-published: August 3, 2018.
doi:10.3324/haematol.2018.188888
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/1/113
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