Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

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 Kenneth, Cavenagh, J., Russell, N., Hills, Robert Kerrin, Kell, J., Jones, G., Nielsen, O. J., Khwaja, A., Thomas, Ian and Clark, R. 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

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution Non-commercial.

Download (1MB) | Preview

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: 26 Jun 2019 20:47
URI: http://orca-mwe.cf.ac.uk/id/eprint/102863

Citation Data

Cited 19 times in Google Scholar. View in Google Scholar

Cited 21 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics