Effect of the presence of P-glycoprotein (MDR1) on the ability of AML patients to achieve complete remission: Results of a meta-analysis of the literature.

Abstract

6586 Background: The expression of P-gp is highly prevalent in acute myeloid leukemia (AML). Current treatment options, including anthracyclines and anthracenediones, are substrates for P-gp. A meta-analysis was carried out to evaluate the influence of P-gp on treatment outcome in AML. Methods: Studies investigating P-gp (function and/or protein and/or mRNA) in AML and reporting the relevant outcomes (in particular, complete remission [CR]) were considered for this meta-analysis. Only patients diagnosed with AML, and who either proceeded to treatment with anthracycline drugs or mitoxantrone, or who had previously been treated with anthracyclines or mitoxantrone, were eligible to be included in the meta-analysis. The primary analysis population for the meta-analysis was the evaluable population (EP), that is, all patients from included studies whose P-gp status was known. Studies for inclusion in the meta-analysis were identified in a thorough literature search, including the PubMed database, using a pre-specified search algorithm. The incidence of P-gp was tabulated by publication and overall. The odds ratio (OD) for CR (positive versus negative P-gp status) was tabulated by publication with 95% confidence interval (CI). Results: 74 studies were included in the analysis. Individual study odds ratios were calculated from 53 studies which provided 4,069 patients evaluable for both CR and P-gp status. The median CR rate across all studies was 65%; CR rates were 78% in Pgp- and 47% in Pgp+ patients. Of the 53 publications, 47 gave OR < 1, including 30 with statistical significance (p < 0.05). Of the 6 publications which gave OR > 1, none reached statistical significance. The overall pooled odds ratio for CR (positive versus negative P-gp status) was 0.302 (95% CI, 0.260-0.350). Conclusions: CR is much less likely to occur in patients with P-gp expression. These patients should be considered for treatment options that are unaffected by P-gp. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Antisoma Antisoma Antisoma