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CHRONIC MYELOGENOUS LEUKEMIA

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

Leukemia volume 36, pages 1336–1342 (2022)Cite this article

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Abstract

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.

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Fig. 1
Fig. 2: Cumulative incidences of imatinib-therapy failure in the training and validation datasets by the IMTF model.
Fig. 3: Failure-free survival in the training and validation datasets by the IMTF model.
Fig. 4: Performance of the predictive model for the probabilities of failure-free survival.

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Acknowledgements

Profs. Rüdiger Hehlmann and Markus Pfirrmann kindly reviewed the typescript. We thank medical staff and patient participants. QJ acknowledges support from the National Natural Science Foundation of China (No. 81770161, No. 81970140). RPG acknowledges support from the National Institute of Health Research (NIHR) Biomedical Research Centre funding scheme.

Funding

Funded, in part, by the National Nature Science Foundation of China (No. 81770161, No. 81970140).

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Authors and Affiliations

  1. Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China

    Xiao-Shuai Zhang, Xiao-Jun Huang & Qian Jiang

  2. Centre for Hematology Research, Department of Immunology and Inflammation, Imperial College London, London, UK

    Robert Peter Gale

  3. Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA

    Mei-Jie Zhang

  4. Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China

    Xiao-Jun Huang & Qian Jiang

  5. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China

    Xiao-Jun Huang

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Contributions

QJ designed the study. QJ and X-SZ collected and analyzed the data. QJ, X-SZ, RPG, M-JZ and X-JH prepared the typescript. All authors approved the final typescript, take responsibility for the content and agreed to submit for publication.

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Correspondence to Xiao-Jun Huang or Qian Jiang.

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RPG is a consultant to BeiGene Ltd., Fusion Pharma LLC, LaJolla NanoMedical Inc., Mingsight Parmaceuticals Inc. and CStone Pharmaceuticals; advisor to Antegene Biotech LLC, Medical Director, FFF Enterprises Inc.; partner, AZAC Inc.; Board of Directors, Russian Foundation for Cancer Research Support; and Scientific Advisory Board: StemRad Ltd.

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The study was approved by the Ethics Committee of People’s Hospital Beijing compliant with principles of the Helsinki Declaration.

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Zhang, XS., Gale, R.P., Zhang, MJ. et al. A predictive scoring system for therapy-failure in persons with chronic myeloid leukemia receiving initial imatinib therapy. Leukemia 36, 1336–1342 (2022). https://doi.org/10.1038/s41375-022-01527-y

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