Analysis of the interaction of induction regimens with p-glycoprotein expression in patients with acute myeloid leukaemia: results from the MRC AML15 trial

Pallis, M, Hills, Robert Kerrin ORCID: https://orcid.org/0000-0003-0166-0062, White, Paul Charles ORCID: https://orcid.org/0000-0002-6562-4696, Grundy, M, Russell, N and Burnett, Alan Kenneth 2011. Analysis of the interaction of induction regimens with p-glycoprotein expression in patients with acute myeloid leukaemia: results from the MRC AML15 trial. Blood Cancer Journal 1 , e23.

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Abstract

Retrospective analyses in non-randomised cohorts suggest that regimens containing fludarabine/Ara C and/or idarubicin/ara C may be more effective than daunorubicin/AraC (DA)-containing regimens in cases of acute myeloid leukaemia (AML) overexpressing p-glycoprotein (Pgp). We prospectively measured Pgp protein and function by flow cytometry in CD45-gated blasts from 434 AML15 trial patients randomised to remission induction therapy with two courses of FLAG-Ida or DA±etoposide (DA/ADE). In all, 34% were positive for Pgp protein and 38% for function. Pgp protein-positive cases had a higher incidence of resistant disease (14% vs 5%), adjusted odds ratio 2.67 (1.14–6.24). There was a trend towards a higher cumulative incidence of relapse at 5 years for Pgp-positive cases (46% vs 55%), adjusted hazard ratio 1.42 (0.98–2.07) (P=0.06). For patients treated with FLAG-Ida, the complete remission (CR) rate was 86% for both Pgp-positive and Pgp-negative patients. In patients treated with DA/ADE, 78% of Pgp-positive and 90% of Pgp-negative cases achieved CR (P=0.06). In analyses of overall survival, there was no interaction between treatment received and Pgp expression. Data for Pgp function followed similar trends. Our data suggest that FLAG-Ida may improve the remission rate for Pgp-positive AML, but the malignant clone is reduced rather than eradicated such that the relapse rate remains high in Pgp-positive patients

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher:	Nature Publishing Group
ISSN:	2044-5385
Last Modified:	06 Jan 2024 03:58
URI:	https://orca.cardiff.ac.uk/id/eprint/49842

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