What are the treatment options for Chronic Myeloid Leukemia (CML)?

From the Guidelines

The treatment of chronic myeloid leukemia (CML) should primarily involve tyrosine kinase inhibitors (TKIs) as first-line therapy, with generic imatinib being the cost-effective initial treatment in chronic phase (CP) patients, as recommended by the European LeukemiaNet 2020 guidelines 1. The goal of therapy is to achieve a complete cytogenetic response within 12 months and a major molecular response (BCR-ABL ≤0.1%) with regular monitoring of BCR-ABL transcript levels every 3 months. Some key points to consider in the treatment of CML include:

• First-line treatment options: imatinib, dasatinib, nilotinib, and bosutinib are available, with generic imatinib being a cost-effective option 1
• Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)-score, and treatment should be adjusted accordingly 1
• Monitoring of response should be done by quantitative polymerase chain reaction whenever possible, and a change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached 1
• Allogeneic transplantation continues to be a therapeutic option, particularly for advanced phase CML, and treatment discontinuation may be considered in patients with durable deep molecular response (DMR) with the goal of achieving treatment-free remission (TFR) 1
• Side effects vary by drug, but may include fluid retention, muscle cramps, diarrhea, and rash for imatinib; QT prolongation and metabolic abnormalities for nilotinib; and pleural effusions for dasatinib 1 It's worth noting that the European LeukemiaNet 2020 guidelines provide the most recent and comprehensive recommendations for the treatment of CML, and should be considered the primary source for guiding treatment decisions 1.

From the FDA Drug Label

BOSULIF is indicated for the treatment of adult patients with: Newly-diagnosed chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML). Chronic phase, accelerated phase (AP), or blast phase (BP) Ph+ CML with resistance or intolerance to prior therapy.

Treatment of Chronic Myeloid Leukemia (CML) can be achieved with:

• Imatinib (PO): for patients in late chronic phase CML and advanced stage CML, including accelerated phase and myeloid blast crisis.
• Bosutinib (PO): for adult patients with newly-diagnosed chronic phase Ph+ CML, or for those with chronic phase, accelerated phase, or blast phase Ph+ CML who have resistance or intolerance to prior therapy 2.

Key points to consider:

• Imatinib (PO) has shown efficacy in achieving hematologic response, major cytogenetic response, and complete cytogenetic response in patients with CML 3.
• Bosutinib (PO) is indicated for the treatment of adult patients with Ph+ CML, including those with resistance or intolerance to prior therapy 2.

From the Research

Treatment Options for Chronic Myeloid Leukemia

• Tyrosine kinase inhibitors (TKIs) are the primary treatment for chronic myeloid leukemia (CML), with options including imatinib, dasatinib, nilotinib, bosutinib, radotinib, and ponatinib 4, 5, 6, 7, 8
• The choice of TKI depends on various factors, including patient comorbidities, side effect profiles, and cost 5, 6, 8

Efficacy and Safety of TKIs

• Second- and third-generation TKIs have been shown to improve clinical responses compared to imatinib, but may be associated with more adverse events such as thrombocytopenia, cardiovascular events, and pancreatic and hepatic effects 4
• Nilotinib has been found to be superior to other TKIs in terms of efficacy, but its safety profile at 12 months is not well established 7
• Dasatinib and nilotinib generate deeper molecular responses than imatinib, particularly among patients with higher risk disease, but this has not translated into a significant survival advantage 6, 8

Individualized Treatment Decision-Making

• Parameters such as disease risk, potency, and toxicity profile of each TKI, as well as patient comorbidities and preferences, should be considered when selecting a first-line TKI 5, 6, 8
• Treatment-free remission is a novel goal in chronic-phase CML, and TKIs can be safely discontinued in select individuals who have maintained deep responses for extended periods 8