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Co-variates associated with outcomes of tyrosine kinase-inhibitor therapy in persons with chronic myeloid leukaemia initially presenting in accelerated phase

Leukemia volume 36, pages 1818–1824 (2022)Cite this article

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Abstract

We interrogated data from 278 consecutive subjects with chronic myeloid leukaemia (CML) presenting in accelerated phase diagnosed by European LeukemiaNet (ELN) criteria receiving initial imatinib (n = 187) or a 2nd-generation tyrosine kinase-inhibitor (2G-TKI; n = 91). In multi-variable analyses, blood and/or bone marrow blasts ≥15% (Hazard ratio [HR] = 3.7 [1.6, 8.5], p = 0.003) and blood basophils <3% (HR = 4.6 [2.0, 10.7], p < 0.001) were significantly-associated with worse transformation-free survival (TFS). Age ≥60 years (HR = 4.3 [1.7, 11.4], p = 0.003), platelet concentration <230 × 10E + 9/L (HR = 4.7 [2.0, 10.7], p < 0.001) and blood and/or bone marrow blasts ≥9% (HR = 3.9 [1.7, 8.7], p = 0.001) were significantly-associated with worse survival. Based on number of adverse prognostic co-variates of TFS and survival, respectively, subjects were classified into the low- (none), intermediate- (one) and high-risk (≥2) cohorts with significant difference in TFS and survival (all p < 0.001). In propensity-score matching analysis subjects initially receiving a 2G-TKI had higher cumulative incidences of cytogenetic and molecular responses but similar TFS and survival to those receiving imatinib. Our data should help inform physicians treating person with CML initially presenting in accelerated phase.

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Fig. 1
Fig. 2: Responses and outcomes of tyrosine kinase inhibitor therapy in subjects with chronic myeloid leukaemia presenting in accelerated phase.
Fig. 3: X-tile analyses to determine the optimal cutoff values of continuous co-variates for predicting transformation-free survival and survival.
Fig. 4: Transformation-free survival and survival by the number of adverse prognostic co-variates.
Fig. 5: Responses and outcomes in persons with chronic myeloid leukaemia presenting in accelerated phase receiving initial imatinib or a 2nd-generation TKI after propensity score matching analysis.

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Acknowledgements

We thank medical staff and patients’ participants. 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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Author notes

  1. These authors contributed equally: Sen Yang, Xiao-shuai Zhang.

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

    Sen Yang, Xiao-shuai Zhang, Xiao-jun Huang & Qian Jiang

  2. Centre for Haematology 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, 100044, Beijing, China

    Xiao-jun Huang

  5. Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, 100044, Beijing, China

    Xiao-jun Huang

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Contributions

QJ designed the study. QJ, SY and X-SZ collected and analyzed the data. QJ, SY, X-SZ, RPG 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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Competing interests

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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Approve by the Ethics Committee of People’s Hospital Beijing compliant with precepts the Helsinki Declaration.

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Yang, S., Zhang, Xs., Gale, R.P. et al. Co-variates associated with outcomes of tyrosine kinase-inhibitor therapy in persons with chronic myeloid leukaemia initially presenting in accelerated phase. Leukemia 36, 1818–1824 (2022). https://doi.org/10.1038/s41375-022-01583-4

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