Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. - Université Claude Bernard Lyon 1 Accéder directement au contenu
Article Dans Une Revue The Lancet Année : 2012

Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study.

Sylvie Castaigne
  • Fonction : Auteur
Cécile Pautas
  • Fonction : Auteur
Emmanuel Raffoux
  • Fonction : Auteur
Ollivier Legrand
  • Fonction : Auteur
Oumedaly Reman
  • Fonction : Auteur
Thierry de Revel
  • Fonction : Auteur
Lauris Gastaud
  • Fonction : Auteur
Noémie de Gunzburg
  • Fonction : Auteur
Nathalie Contentin
  • Fonction : Auteur
Jean-Pierre Marolleau
  • Fonction : Auteur
  • PersonId : 887235
  • IdRef : 06981676X
Ahmad Aljijakli
  • Fonction : Auteur
Pierre Fenaux
  • Fonction : Auteur
Hervé Dombret
Non Renseigné
  • Fonction : Auteur

Résumé

BACKGROUND: The results of the addition of gemtuzumab ozogamicin, an anti-CD33 antibody conjugate, to the standard treatment for patients with acute myeloid leukaemia in phase 3 trials were contradictory. We investigated whether the addition of low fractionated-dose gemtuzumab ozogamicin to standard front-line chemotherapy would improve the outcome of patients with this leukaemia without causing excessive toxicity. METHODS: In a phase 3, open-label study, undertaken in 26 haematology centres in France, patients aged 50-70 years with previously untreated de novo acute myeloid leukaemia were randomly assigned with a computer-generated sequence in a 1:1 ratio with block sizes of four to standard treatment (control group) with or without five doses of intravenous gemtuzumab ozogamicin (3 mg/m(2) on days 1, 4, and 7 during induction and day 1 of each of the two consolidation chemotherapy courses). The primary endpoint was event-free survival (EFS). Secondary endpoints were relapse-free (RFS), overall survival (OS), and safety. Analysis was by intention to treat. This study is registered with EudraCT, number 2007-002933-36. FINDINGS: 280 patients were randomly assigned to the control (n=140) and gemtuzumab ozogamicin groups (n=140), and 139 patients were analysed in each group. Complete response with or without incomplete platelet recovery to induction was 104 (75%) in the control group and 113 (81%) in the gemtuzumab ozogamicin group (odds ratio 1*46, 95% CI 0*20-2*59; p=0*25). At 2 years, EFS was estimated as 17*1% (10*8-27*1) in the control group versus 40*8% (32*8-50*8) in the gemtuzumab ozogamicin group (hazard ratio 0*58, 0*43-0*78; p=0*0003), OS 41*9% (33*1-53*1) versus 53*2% (44*6-63*5), respectively (0*69, 0*49-0*98; p=0*0368), and RFS 22*7% (14*5-35*7) versus 50*3% (41*0-61*6), respectively (0*52, 0*36-0*75; p=0*0003). Haematological toxicity, particularly persistent thrombocytopenia, was more common in the gemtuzumab ozogamicin group than in the control group (22 [16%] vs 4 [3%]; p<0*0001), without an increase in the risk of death from toxicity. INTERPRETATION: The use of fractionated lower doses of gemtuzumab ozogamicin allows the safe delivery of higher cumulative doses and substantially improves outcomes in patients with acute myeloid leukaemia. The findings warrant reassessment of gemtuzumab ozogamicin as front-line therapy for acute myeloid leukaemia. FUNDING: Wyeth (Pfizer).

Domaines

Cancer

Dates et versions

hal-01056520 , version 1 (20-08-2014)

Identifiants

Citer

Sylvie Castaigne, Cécile Pautas, Christine Terré, Emmanuel Raffoux, Dominique Bordessoule, et al.. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study.. The Lancet, 2012, 379 (9825), pp.1508-16. ⟨10.1016/S0140-6736(12)60485-1⟩. ⟨hal-01056520⟩
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