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CHRONIC MYELOID LEUKEMIA

What is the impact of failing to achieve TKI therapy milestones in chronic myeloid leukemia

Leukemia volume 37, pages 2324–2325 (2023)Cite this article

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This article has been updated

The breakthrough research with the BCR::ABL1 tyrosine kinase inhibitors (TKIs) transformed the therapy of chronic myeloid leukemia (CML) [1, 2]. CML experts began aiming to achieve quick, deep molecular responses in their patients with the dual goals of improving survival and achieving treatment-free remission [3, 4]. To achieve the best possible outcomes, several expert bodies such as the European LeukemiaNet (ELN) and the National Comprehensive Cancer Network identified milestones intended to guide hematologists when to declare a specific TKI a failure, thereby necessitating a switch to another TKI [5, 6]. Now that there are more mature data, it is relevant to consider the fate of patients who fail to meet these milestones [7, 8].

In this issue, Lauseker et al. analyze the survival of 1342 patients with newly diagnosed chronic phase CML treated with imatinib, and the subset who failed to meet the ELN milestones [9]. Those with failure at 3–6 months (BCR::ABL1 transcripts on the International Scale [IS] >10%) or at 12–24 months (BCR::ABL1 transcripts [IS] >1%) had a 10–12 year survival of about 70%. This is 10% lower than those who met the milestones, but encouraging nevertheless. Changing TKI therapy (27%; resistant CML [failure resistance] 10% at 10 years; adverse events 17% at 10 years) did not significantly improve survival. The authors conclude that their analyses confirm the value of the response milestones, and that among patients with resistance, an individualized approach is needed rather than mandating a change in therapy [9]. The question is whether the data justify the ominous ELN label of “failure.”

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Change history

  • 10 October 2023

    The supertitle has been corrected.

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  1. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Hagop M. Kantarjian

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HMK contributes to all aspects of the commentary.

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Correspondence to Hagop M. Kantarjian.

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HMK reports research grants and honoraria from AbbVie, Amgen, Amphista, Ascentage, Astellas, Biologix, Curis, Daiichi-Sankyo, Immunogen, Ipsen Biopharmaceuticals, Jazz, KAHR Medical, Labcorp, Novartis, Pfizer, Shenzhen Target Rx, Stemline, Takeda.

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Kantarjian, H.M. What is the impact of failing to achieve TKI therapy milestones in chronic myeloid leukemia. Leukemia 37, 2324–2325 (2023). https://doi.org/10.1038/s41375-023-02053-1

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