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, 04/24/2012

Castaigne S et al. – 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.

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.

Results

  • 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.

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