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Tyrosine Kinase Inhibitor Discontinuation in Chronic Myeloid Leukemia: Strategies to Optimize Success and New Directions

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Abstract

Purpose of Review

The discovery that patients suffering from chronic myeloid leukemia who obtain deep and long-lasting molecular responses upon treatment with tyrosine kinase inhibitors may maintain their disease silent for many years after therapy discontinuation launched the era of treatment-free remission as a key management goal in clinical practice. The purpose of this review on treatment-free remission is to discuss clinical advances, highlight knowledge gaps, and describe areas of research.

Recent Findings

Patients in treatment-free remission are a minority, and it is believed that some may still retain a reservoir of leukemic stem cells; thus, whether they can be considered as truly cured is uncertain. Strengthening BCR::ABL1 inhibition increases deep molecular responses but is not sufficient to improve treatment-free remission, and we lack biomarkers to identify and specifically target residual cells with aggressive potential. Another level of complexity resides in the intra- and inter-patient clonal heterogeneity of minimal residual disease and characteristics of the bone marrow environment.

Summary

Finding determinants of deep molecular responses achievement and elucidating varying biological mechanisms enabling either post-tyrosine kinase inhibitor chronic myeloid leukemia control or relapse may help develop innovative and safe therapies. In the light of the increasing prevalence of CML, targeting the residual leukemic stem cell pool is thought to be the key.

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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Authors and Affiliations

  1. Service d’Hématologie Adulte, Hôpital Saint-Louis APHP, 75010, Paris, France

    Delphine Rea, Sofiane Fodil, Etienne Lengline & Emmanuel Raffoux

  2. France Intergroupe Des Leucémies Myéloïdes Chroniques FiLMC, Paris, France

    Delphine Rea & Jean-Michel Cayuela

  3. Laboratoire Central d’Hématologie, Hôpital Saint-Louis APHP, Paris, France

    Jean-Michel Cayuela

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Rea, D., Fodil, S., Lengline, E. et al. Tyrosine Kinase Inhibitor Discontinuation in Chronic Myeloid Leukemia: Strategies to Optimize Success and New Directions. Curr Hematol Malig Rep (2024). https://doi.org/10.1007/s11899-024-00728-9

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