Resistance prediction in AML: analysis of 4601 patients from MRC/NCRI, HOVON/SAKK, SWOG and MD Anderson Cancer Center.

Abstract

Therapeutic resistance remains the principal problem in acute myeloid leukemia (AML). We used area under receiver-operating characteristic curves (AUCs) to quantify our ability to predict therapeutic resistance in individual patients, where AUC=1.0 denotes perfect prediction and AUC=0.5 denotes a coin flip, using data from 4601 patients with newly diagnosed AML given induction therapy with 3+7 or more intense standard regimens in UK Medical Research Council/National Cancer Research Institute, Dutch-Belgian Cooperative Trial Group for Hematology/Oncology/Swiss Group for Clinical Cancer Research, US cooperative group SWOG and MD Anderson Cancer Center studies. Age, performance status, white blood cell count, secondary disease, cytogenetic risk and FLT3-ITD/NPM1 mutation status were each independently associated with failure to achieve complete remission despite no early death ('primary refractoriness'). However, the AUC of a bootstrap-corrected multivariable model predicting this outcome was only 0.78, indicating only fair predictive ability. Removal of FLT3-ITD and NPM1 information only slightly decreased the AUC (0.76). Prediction of resistance, defined as primary refractoriness or short relapse-free survival, was even more difficult. Our limited ability to forecast resistance based on routinely available pretreatment covariates provides a rationale for continued randomization between standard and new therapies and supports further examination of genetic and posttreatment data to optimize resistance prediction in AML.

• Authors: R B Walter, M Othus, A K Burnett, B Löwenberg, H M Kantarjian, G J Ossenkoppele, R K Hills, F Ravandi, T Pabst, A Evans, S R Pierce, M-C Vekemans, F R Appelbaum, E H Estey
• Journal: Leukemia (Leukemia) Vol. 29 Issue 2 Pg. 312-20 (Feb 2015) ISSN: 1476-5551 [Electronic] England
• PMID: 25113226 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Area Under Curve
• Clinical Trials as Topic
• Disease-Free Survival
• Drug Resistance, Neoplasm
• Female
• Humans
• Leukemia, Myeloid, Acute (diagnosis, drug therapy)
• Male
• Middle Aged
• Multivariate Analysis
• Mutation
• Neoplasm, Residual
• Nucleophosmin
• Prognosis
• Regression Analysis
• Remission Induction
• Treatment Outcome
• Young Adult