What is the treatment for Chronic Myeloid Leukemia (CML)?

From the Guidelines

Chronic Myeloid Leukemia (CML) treatment primarily involves 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 in 2020 1. The treatment goals for CML include achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR).

• First-line treatment options include imatinib, dasatinib, nilotinib, and bosutinib, with the choice of TKI depending on patient risk status, contraindications, and side effects.
• Patient risk status at diagnosis should be assessed using the new EUTOS long-term survival (ELTS)-score, and monitoring of response should be done by quantitative polymerase chain reaction whenever possible.
• A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached, with greater than 10% BCR-ABL1 at 3 months indicating treatment failure when confirmed.
• Allogeneic transplantation continues to be a therapeutic option, particularly for advanced phase CML, and TKI treatment should be withheld during pregnancy.
• Treatment discontinuation may be considered in patients with durable DMR, with the goal of achieving TFR, as supported by the NCCN clinical practice guidelines in oncology 1. Some key considerations for TKI selection include:
• Imatinib 400mg daily is a standard initial treatment, with second-generation TKIs like nilotinib, dasatinib, and bosutinib offering alternatives with potentially faster and deeper responses.
• Side effects vary by drug, but may include fluid retention, muscle cramps, and cytopenias with imatinib; pleural effusions with dasatinib; and QT prolongation with nilotinib.
• For patients who fail multiple TKIs, ponatinib or asciminib may be options, though stem cell transplantation remains the only potential cure for eligible patients, as noted in the ESMO clinical practice guidelines for diagnosis, treatment, and follow-up 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 for Chronic Myeloid Leukemia (CML): The treatment includes imatinib (PO) 2 and bosutinib (PO) 3.
• Key treatment options:
  • Imatinib (PO) for Late Chronic Phase CML and Advanced Stage CML
  • Bosutinib (PO) for newly-diagnosed chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML) and for chronic phase, accelerated phase (AP), or blast phase (BP) Ph+ CML with resistance or intolerance to prior therapy.

From the Research

Treatment Options for Chronic Myeloid Leukemia (CML)

• The primary treatment for CML involves the use of tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, nilotinib, and bosutinib 4, 5, 6, 7, 8.
• Imatinib is considered the gold standard for first-line treatment, but second- and third-generation TKIs have been developed for patients who are resistant or intolerant to imatinib 4.
• The choice of TKI depends on various factors, including the patient's response to treatment, presence of mutations, and tolerability of side effects 5, 6, 7.
• Therapeutic drug monitoring is recommended to optimize TKI dosage and minimize adverse events 5.
• Bosutinib is a second-generation TKI approved for the treatment of patients with Ph-positive CML who are intolerant or resistant to other TKIs 6.
• The European LeukemiaNet recommendations suggest that the clinical response of CML patients receiving TKI therapy should be evaluated after 3,6, and 12 months 5, 8.
• Treatment discontinuation and treatment-free remission (TFR) are possible for patients who achieve a sustained deep molecular response (DMR) 8.

Tyrosine Kinase Inhibitors (TKIs) Used in CML Treatment

• Imatinib: first-line treatment, target plasma concentration above 1000 ng/mL 5.
• Nilotinib: second-generation TKI, target plasma concentration of 500 ng/mL for patients with UGT1A1*6/*6, *6/*28, or *28/28 genotype, and 800 ng/mL for patients with UGT1A11 allele 5.
• Dasatinib: second-generation TKI, recommended to maintain a higher Cmax or C₂ (above 50 ng/mL) and a lower C₀ (less than 2.5 ng/mL) to avoid pleural effusion 5.
• Bosutinib: second-generation TKI, effective in cases involving most imatinib-resistant mutations, except T315I and V299L mutations 6.

Considerations for TKI Treatment

• Patient comorbidities and contraindications of all TKIs must be considered 8.
• Risk profile at diagnosis should be assessed with the EUTOS score for long-term survival (ELTS) 8.
• Monitoring of response is by polymerase chain reaction (PCR), and cytogenetics is still required in certain cases 8.
• TKIs are contraindicated during pregnancy 8.