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

RB Walter, M Othus, AK Burnett, Bob Löwenberg, HM Kantarjian, GJ Ossenkoppele, RK Hills, F Ravandi, T Pabst, A Evans, SR Pierce, MC Vekemans, FR Appelbaum, EH Estey

Research output: Contribution to journalArticleAcademicpeer-review

107 Citations (Scopus)

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.
Original languageUndefined/Unknown
Pages (from-to)312-320
Number of pages9
JournalLeukemia
Volume29
Issue number2
DOIs
Publication statusPublished - 2015

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