Defining the dose of gemtuzumab ozogamicin in combination with induction chemotherapy in acute myeloid leukemia: a comparison of 3 mg/m2 with 6 mg/m2 in the NCRI AML17 trial

Burnett, Alan, Cavenagh, Jamie, Russell, Nigel, Hills, Robert ORCID: https://orcid.org/0000-0003-0166-0062, Kell, Jonathan, Jones, Gail, Nielsen, Ove Juul, Khwaja, Asim, Thomas, Ian and Clark, Richard 2016. Defining the dose of gemtuzumab ozogamicin in combination with induction chemotherapy in acute myeloid leukemia: a comparison of 3 mg/m2 with 6 mg/m2 in the NCRI AML17 trial. Haematologica 101 (6) , pp. 724-731. 10.3324/haematol.2016.141937

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Abstract

A recent source data meta-analysis of randomised trials in adults assessing the immunoconjugate, gemtuzumab ozogamicin combined with standard chemotherapy in acute myeloid leukaemia showed a significant survival benefit in patients without an adverse karyotype. It is not clear whether the optimal dose should be 3mg/m2 or 6mg/m2. In this study we randomised 788 patients to a single dose of gemtuzumab ozogamicin 3mg/m2 or 6mg/m2 with the first course of induction therapy. We found that the rate of complete remission was higher with 3mg/m2 (82% vs 76%;odds ratio 1.46 (1.04-2.06) p=0.03), but this was balanced by a higher rate of complete remission with incomplete peripheral blood count recovery in the 6mg/m2 treatment (10% vs 7%) resulting in similar overall response rate (89% vs 86%;hazard ratio 1.34 (0.88-2.04) p=0.17). Overall, relapse and survival at 4 years were not different between the arms (46% vs 54%; hazard ratio 1.17 (0.94-1.45),p=0.5) and 50% vs 47% (hazard ratio 1.10 (0.90-1.34),p=0.3). The 30 and 60 day mortality was significantly higher in the 6mg/m2 recipients (7% vs 3%; hazard ratio 2.07 (1.11-3.87),p=0.02) and 9% vs 5%; (hazard ratio 1.00 (1.17-3.39),p=0.01), which in addition was associated with a higher rate of veno-occlusive disease (5.6% vs 0.5%,p<0.0001). Our conclusion from this trial is that there is no advantage for using a single dose of 6mg/m2 of gemtuzumab ozogamicin in combination with induction chemotherapy when compared with a 3mg/m2 dose, with respect to response, disease free and survival, either overall, or in any disease subgroup. AML17 was registered as ISRCTN55675535.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Ferrata Storti Foundation
ISSN:	0390-6078
Date of First Compliant Deposit:	25 October 2018
Date of Acceptance:	23 February 2016
Last Modified:	20 Sep 2023 16:44
URI:	https://orca.cardiff.ac.uk/id/eprint/102863

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