A predictive scoring system for therapy-failure in persons with chronic myeloid leukemia receiving initial imatinib therapy

• Published in: Leukemia Vol. 36; no. 5; pp. 1336 - 1342
• Main Authors: Zhang, Xiao-Shuai, Gale, Robert Peter, Zhang, Mei-Jie, Huang, Xiao-Jun, Jiang, Qian
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2022; Nature Publishing Group
• Subjects: 631/67/1990/283/1896; 692/499; Antineoplastic Agents - therapeutic use; Blood levels; Calibration; Cancer Research; Chronic myeloid leukemia; Critical Care Medicine; Datasets; Decision analysis; Failure; Hematology; Hemoglobin; Humans; Imatinib; Imatinib Mesylate - therapeutic use; Inhibitor drugs; Intensive; Internal Medicine; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase - drug therapy; Leukocytes (basophilic); Medicine; Medicine & Public Health; Myeloid leukemia; Oncology; Physicians; Progression-Free Survival; Protein Kinase Inhibitors - therapeutic use; Regression coefficients; Risk; Survival; Targeted cancer therapy; Therapy; Training; Treatment Outcome
• ISSN: 0887-6924; 1476-5551; 1476-5551
• DOI: 10.1038/s41375-022-01527-y

Data from 1,364 consecutive subjects with chronic-phase chronic myeloid leukemia (CML) receiving initial imatinib-therapy were interrogated to identify co-variates predicting therapy failure. Subjects were randomly divided into training ( n  = 908) and validation datasets ( n  = 456). In the training dataset, WBC count ≥120 × 10E + 9/L, haemoglobin concentration <115 g/L, blood basophils ≥12% and European Treatment and Outcome Study for CML Long-Term Survival (ELTS) risk score were significantly-associated with failure-free survival (FFS). Each co-variate was assigned 1 point to develop the imatinib-therapy failure (IMTF) model except ELTS high-risk category which was assigned 2 points based on multi-variable regression coefficients. Area under receiver-operator characteristic curve values in the IMTF model for 1-, 3- and 5-year FFS were 0.79–0.84 in the training dataset and 0.78–0.85 in the validation dataset. Calibration plots showed high agreement between predicted and observed outcomes. Decision curve analyses indicated subjects benefited from clinical use of this model. Cumulative incidences of imatinib-therapy failure and probabilities of FFS among the 5 risk cohorts (very low-, low-, intermediate-, high- and very high-risk) using the IMTF model were significantly different (all p values < 0.001). The IMTF model also correlated with probabilities of progression-free survival and survival (all p values < 0.001). These data should help physicians optimize TKI-therapy strategy at diagnosis in persons with chronic phase CML.