Update on the management of chronic myeloid leukemia: current best practice and future directions

ABSTRACT

Introduction: Tyrosine kinase inhibitor (TKI) therapy has dramatically improved survival for patients with chronic myeloid leukemia (CML). The focus of CML therapy is now shifting to improvement in quality of life, reduction of toxicity, and economic burden. TKI therapy was once considered lifelong therapy; however studies in recent years have shown that cessation of TKI therapy without loss of molecular response, known as treatment-free remission (TFR), is achievable in a subset of CML patients. Another important development is the introduction of second- and third-generation TKIs of increased potency, each with a distinct toxicity profile but the potential to salvage patients with poor responses.

Areas covered: Data on approved TKIs, including survival outcomes and toxicity profiles, are reviewed. TFR data and its application in clinical practice are discussed. Prevention and management of toxicities, with focus on long-term cardiovascular toxicity with TKIs, are also reviewed.

Expert opinion: Choice of first-line TKI needs to be an individualized decision. Factors to consider include desired goal of care, patient comorbidities, and access to therapy. Patients should be educated on TKI toxicities and the potential for TFR. As second-generation TKIs are increasingly used, clinicians must be cognizant of their toxicities and proactive in prevention of adverse events.

KEYWORDS:

• Chronic myeloid leukemia
• CML
• treatment-free remission
• tyrosine kinase inhibitor
• cardiotoxicity

Article highlights

• Imatinib, Dasatinib, Nilotinib, and Bosutinib are approved for first-line CML therapy.

• Ponatinib is also available for patients in whom no other TKI is indicated or with the presence of a T315I mutation.

• Each of the TKIs has a distinct toxicity profile, which is of importance in counselling newly diagnosed patients, clinical surveillance, and identification of adverse events.

• Cardiovascular assessment and risk-factor management is of increasing importance for patients receiving TKI therapy, particularly Nilotinib and Ponatinib.

• Cessation of therapy has been shown to be safe for patients with sustained DMR provided they have appropriate follow-up and molecular monitoring. TFR is achievable in up to 50% of these patients.

• Therapy of advanced phase CML remains challenging and patients should be referred for expert opinion and clinical trials where possible.

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Declaration of interest

J Lipton is a consultant for and received research funding from Ariad, Bristol-Myers Squibb, Novartis, and Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Review disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.