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CHRONIC MYELOGENOUS LEUKEMIA

Predictive scoring systems for molecular responses in persons with chronic phase chronic myeloid leukemia receiving initial imatinib therapy

Leukemia volume 36, pages 2042–2049 (2022)Cite this article

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Abstract

It is vital for physicians and persons with chronic myeloid leukemia (CML) to accurately predict the likelihood of achieving a major molecular response (MMR) and a deep molecular response (DMR; at least MR4) at the start of imatinib-therapy, which could help in decision making of treatment goals and strategies. To answer this question, we interrogated data from 1369 consecutive subjects with chronic phase CML receiving initial imatinib-therapy to identify predictive co-variates. Subjects were randomly-assigned to training (n = 913) and validation (n = 456) datasets. Male sex, higher WBC concentration, lower haemoglobin concentration, higher percentage blood blasts and larger spleen size were significantly-associated with lower cumulative incidences of MMR and MR4 in training dataset. Using Fine-Gray model, we developed the predictive scoring systems for MMR and MR4 which classified subjects into the low-, intermediate- and high-risk cohorts with significantly-different cumulative incidences of MMR and MR4 with good predictive discrimination and accuracy in training and validation cohorts with high area under the receiver-operator characteristic curve (AUROC) values. These data may help physicians decide appropriateness of initial imatinib therapy.

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Fig. 1
Fig. 2: Cumulative incidences of MMR and MR4 using the predictive scoring systems in the training dataset.
Fig. 3: Cumulative incidences of MMR and MR4 using the predictive scoring systems in the validation dataset.
Fig. 4: Concordance analyses of the predictive scoring systems for MMR and MR4.
Fig. 5: The impact of switching TKI-therapy on responses by the predictive scoring systems for MMR and MR4.

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Acknowledgements

We thank medical staff and patient participants. QJ acknowledges support from the National Natural Science Foundation of China (No. 81970140). RPG acknowledges support from the National Institute of Health Research (NIHR) Biomedical Research Centre funding scheme. Funded, in part, by the National Nature Science Foundation of China (No. 81970140) and CAMS Innovation Fund for Medical Sciences (CIFMS) (No. 2019-I2M-5-034).

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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, Zi-yu Li, Meng-yu 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. Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China

    Xiao-jun Huang & Qian Jiang

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

    Xiao-jun Huang

  5. Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, Beijing, China

    Xiao-jun Huang

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Contributions

QJ designed the study. QJ, XSZ, ZYL, and MYZ collected and analyzed the data. QJ, XJH, XSZ, RPG, ZYL, and MYZ prepared the typescript. All authors approved the final typescript, take responsibility for the content, and agree 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 NexImmune Inc. and Ananexa Pharma Ascentage Pharm Group, Antengene 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., Li, Zy. et al. Predictive scoring systems for molecular responses in persons with chronic phase chronic myeloid leukemia receiving initial imatinib therapy. Leukemia 36, 2042–2049 (2022). https://doi.org/10.1038/s41375-022-01616-y

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