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

详细信息	查看全文 | 推荐本文 |

• 作者：Prof Sylvie Castaigne ; MD^a ; ^{scastaigne@ch-versailles.fr} ; Cé ; cile Pautas ; MD^b ; Christine Terré ; MD^c ; Emmanuel Raffoux ; MD^d ; Prof Dominique Bordessoule ; MD^e ; Prof Jean-Noel Bastie ; PhD^f ; Prof Ollivier Legrand ; PhD^g ; Xavier Thomas ; MD^h ; Pascal Turlure ; MD^e ; Oumedaly Reman ; MDⁱ ; Prof Thierry de Revel ; MD^j ; Lauris Gastaud ; MD^k ; Noé ; mie de Gunzburg ; MD^a ; Nathalie Contentin ; MD^l ; Estelle Henry^a ; Prof Jean-Pierre Marolleau ; MD^m ; Ahmad Aljijakli ; MDⁿ ; Prof Philippe Rousselot ; PhD^a ; Prof Pierre Fenaux ; PhD^o ; Prof Claude Preudhomme ; PhD^p ; Prof Sylvie Chevret ; PhD^q ; Prof Hervé ; Dombret ; MD^d ; for the Acute Leukemia French Association
• 刊名：The Lancet
• 出版年：2012
• 期刊代码：182_01406736
• 类别：med
• 出版时间：21-27 April, 2012
• 卷：379
• 期：9825
• 页码：1508-1516
• 文件大小：286 K

摘要

| Figures/TablesFigures/Tables | ReferencesReferences

Summary

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/m² 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路46, 95%CI 0路20-2路59; p=0路25). At 2 years, EFS was estimated as 17路1%(10路8-27路1) in the control group versus 40路8%(32路8-50路8) in the gemtuzumab ozogamicin group (hazard ratio 0路58, 0路43-0路78; p=0路0003), OS 41路9%(33路1-53路1) versus 53路2%(44路6-63路5), respectively (0路69, 0路49-0路98; p=0路0368), and RFS 22路7%(14路5-35路7) versus 50路3%(41路0-61路6), respectively (0路52, 0路36-0路75; p=0路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路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).