Clinical Review

Chronic Myeloid Leukemia: Selecting First-line TKI Therapy



From the Moffitt Cancer Center, Tampa, FL.


  • Objective: To outline the approach to selecting a tyrosine kinase inhibitor (TKI) for initial treatment of chronic myeloid leukemia (CML) and monitoring patients following initiation of therapy.
  • Methods: Review of the literature and evidence-based guidelines.
  • Results: The development and availability of TKIs has improved survival for patients diagnosed with CML. The life expectancy of patients diagnosed with chronic-phase CML (CP-CML) is similar to that of the general population, provided they receive appropriate TKI therapy and adhere to treatment. Selection of the most appropriate first-line TKI for newly diagnosed CP-CML requires incorporation of the patient’s baseline karyotype and Sokal or EURO risk score, and a clear understanding of the patient’s comorbidities. The adverse effect profile of all TKIs must be considered in conjunction with the patient’s ongoing medical issues to decrease the likelihood of worsening their current symptoms or causing a severe complication from TKI therapy. After confirming a diagnosis of CML and selecting the most appropriate TKI for first-line therapy, close monitoring and follow-up are necessary to ensure patients are meeting the desired treatment milestones. Responses in CML can be assessed based on hematologic parameters, cytogenetic results, and molecular responses.
  • Conclusion: Given the successful treatments available for patients with CML, it is crucial to identify patients with this diagnosis; ensure they receive a complete, appropriate diagnostic workup including a bone marrow biopsy and aspiration with cytogenetic testing; and select the best therapy for each individual patient.

Keywords: chronic myeloid leukemia; CML; tyrosine kinase inhibitor; TKI; cancer; BCR-ABL protein.

Chronic myeloid leukemia (CML) is a rare myeloproliferative neoplasm that is characterized by the presence of the Philadelphia (Ph) chromosome and uninhibited expansion of bone marrow stem cells. The Ph chromosome arises from a reciprocal translocation between the Abelson (ABL) region on chromosome 9 and the breakpoint cluster region (BCR) of chromosome 22 (t(9;22)(q34;q11.2)), resulting in the BCR-ABL1 fusion gene and its protein product, BCR-ABL tyrosine kinase.1 BCR-ABL has constitutive tyrosine kinase activity that promotes growth, replication, and survival of hematopoietic cells through downstream pathways, which is the driving factor in the pathogenesis of CML.1

CML is divided into 3 phases based on the number of myeloblasts observed in the blood or bone marrow: chronic, accelerated, and blast. Most cases of CML are diagnosed in the chronic phase (CP), which is marked by proliferation of primarily the myeloid element.

Typical treatment for CML involves lifelong use of oral BCR-ABL tyrosine kinase inhibitors (TKIs). Currently, 5 TKIs have regulatory approval for treatment of this disease. The advent of TKIs, a class of small molecules targeting the tyrosine kinases, particularly the BCR-ABL tyrosine kinase, led to rapid changes in the management of CML and improved survival for patients. Patients diagnosed with chronic-phase CML (CP-CML) now have a life expectancy that is similar to that of the general population, as long as they receive appropriate TKI therapy and adhere to treatment. As such, it is crucial to identify patients with CML; ensure they receive a complete, appropriate diagnostic workup; and select the best therapy for each patient.


According to SEER data estimates, 8430 new cases of CML were diagnosed in the United States in 2018. CML is a disease of older adults, with a median age of 65 years at diagnosis, and there is a slight male predominance. Between 2011 and 2015, the number of new CML cases was 1.8 per 100,000 persons. The median overall survival (OS) in patients with newly diagnosed CP-CML has not been reached.2 Given the effective treatments available for managing CML, it is estimated that the prevalence of CML in the United States will plateau at 180,000 patients by 2050.3


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