Management of Chronic Myeloid Leukemia that is Intolerant or Resistant to Front-Line Treatment


  • Lisa Bilston, MD, FRCPC Division of Hematology and Hematologic Malignancies, University of Calgary
  • Kareem Jamani, MD, FRCPC Division of Hematology and Hematologic Malignancies, University of Calgary



With advances in treatment for chronic myeloid leukemia (CML), the natural history of chronic phase (CP) CML has changed, with most individuals expected to live a normal life expectancy. The goal of therapy for most is to achieve a long-term deep molecular response (DMR) with the potential for medication discontinuation and treatment-free remission (TFR).1 Currently, six oral therapies have been approved for CP-CML in Canada: (1) imatinib, a first-generation tyrosine kinase inhibitor (TKI); (2) dasatinib, (3) nilotinib, and (4) bosutinib, the second-generation TKIs (2G-TKIs); (5) ponantinib, a third-generation TKI; and (6) asciminib, specifically targeting the ABL Myristoyl pocket (STAMP) inhibitor. Classically, treatment for CP-CML has consisted of front-line imatinib and switching to a 2G-TKI upon treatment resistance or intolerance. Increasingly, patients are being prescribed an upfront 2G-TKI with the goal of achieving quicker and deeper molecular remissions and a TFR.2 Challenges arise in CML when treatment with either two TKIs (imatinib + 2G-TKI) or one 2G-TKI fails, given the lack of evidence to inform clinical decision-making at this juncture. This paper aims to define TKI failure and help guide the selection of second-line treatment after failure of front-line therapy. 

Author Biographies

Lisa Bilston, MD, FRCPC, Division of Hematology and Hematologic Malignancies, University of Calgary

Dr. Lisa Bilston is currently completing residency in Hematology at the University of Calgary, where she also completed medical school and Internal Medicine training. She will be starting as a hematologist with the Central Alberta Cancer Center and Red Deer Regional Hospital. 

Kareem Jamani, MD, FRCPC, Division of Hematology and Hematologic Malignancies, University of Calgary

Dr. Kareem Jamani is a clinical assistant professor at the University of Calgary and an attending physician at the Tom Baker Cancer Centre and Alberta Blood & Marrow Transplant Program. His clinical practice comprises myeloid neoplasms, acute leukemias and allogeneic stem cell transplant. Dr. Jamani’s research interests include post-transplant toxicities, survivorship, and quality of life. 


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How to Cite

Bilston L, Jamani K. Management of Chronic Myeloid Leukemia that is Intolerant or Resistant to Front-Line Treatment. Can Hematol Today [Internet]. 2024 Jun. 27 [cited 2024 Jul. 23];3(2):31–39. Available from: