How I treat chronic-phase chronic myelogenous leukemia

When imatinib, the first tyrosine kinase inhibitor (TKI) developed for use in chronic myelogenous leukemia (CML), was approved in 2001, the treatment of this disease was forever changed. Significant reductions in the molecular burden of disease were seen with the first-generation TKI imatinib and, with the addition of dasatinib (2006), nilotinib (2007), bosutinib (2012), and ponatinib (2013), deeper and more rapid reductions were noted. Physicians could begin to tailor TKI therapy to individual patients, and patients who did not respond to or could not tolerate first-line therapy now had options. Importantly, the number of patients who developed accelerated or blast phase disease decreased dramatically. Research in CML continues to evolve; by presenting illustrative cases, this article reviews some of the newer aspects of clinical care in this disease. Updated information regarding bosutinib and asciminib, the latter currently in clinical trials, will be presented; bosutinib is of particular interest as the drug's transit through the United States Food and Drug Administration highlights the question of what is considered optimal response to TKI therapy. The challenge of understanding the cardiac safety data of ponatinib and the unique dosing schedule based on individual response will be discussed. Lastly, two cases will focus on features of TKI treatment that, remarkably, have become part of the treatment algorithm: family planning for women with CML and stopping therapy after meeting a specific treatment milestone.

Automated summary

The introduction of imatinib, the first tyrosine kinase inhibitor (TKI) for chronic myelogenous leukemia (CML), revolutionized the treatment of this disease. Subsequent generations of TKIs, such as dasatinib, nilotinib, bosutinib, and ponatinib, have further improved treatment outcomes. Individualized TKI therapy has provided options for patients who do not respond to or cannot tolerate first-line treatment, leading to a significant decrease in the number of patients progressing to advanced stages of the disease. This article reviews newer aspects of clinical care in CML, including the use of bosutinib and asciminib, the cardiac safety of ponatinib, and the consideration of family planning and treatment discontinuation.