What is the initial treatment for chronic myeloid leukemia (CML)?

Initial Treatment for Chronic Myeloid Leukemia (CML)

Tyrosine kinase inhibitors (TKIs) are the standard initial treatment for newly diagnosed chronic phase CML, with imatinib 400 mg daily being the most cost-effective first-line option for most patients, while second-generation TKIs are preferred for intermediate or high-risk patients. 1

Risk Assessment and TKI Selection

Risk stratification is essential before selecting the appropriate TKI therapy:

• Use validated risk assessment tools such as:
  • EUTOS Long-Term Survival (ELTS) score
  • Sokal score
  • Euro score 1

First-line TKI Options:

1. Imatinib 400 mg daily

   • Standard approach for low-risk patients 2
   • Most cost-effective option
   • Well-established long-term safety profile
   • Progression-free survival of 84% and overall survival of 88% after 6 years 2

2. Second-generation TKIs (for intermediate or high-risk patients):

   • Nilotinib 300 mg twice daily
   • Dasatinib 100 mg daily
   • Bosutinib 400 mg daily
   • Advantages: faster and deeper molecular responses, lower risk of disease progression 1

Patient-Specific Considerations for TKI Selection

Consider these factors when selecting the appropriate TKI:

• Comorbidities:

  • Avoid dasatinib in patients with pulmonary diseases or risk of pleural effusion
  • Avoid nilotinib in patients with cardiovascular diseases, diabetes, cerebrovascular diseases, or peripheral arteriopathy
  • Monitor QT interval with all TKIs 1

• Age and Treatment Goals:

  • For younger patients seeking treatment-free remission, second-generation TKIs may be preferred
  • For older patients with comorbidities, imatinib may be preferred due to its established safety profile 1

• Pregnancy Planning:

  • For young female patients planning pregnancy, consider second-generation TKIs to achieve deep molecular response more quickly, allowing for treatment-free remission
  • TKI therapy should be suspended during pregnancy 1

Monitoring Response to Treatment

Regular monitoring is crucial to assess treatment efficacy:

• Molecular monitoring: Quantitative PCR every 3 months
• Cytogenetic monitoring: At 3,6,12, and 18 months until complete cytogenetic response is achieved 1

Key Response Milestones:

• BCR-ABL1 ≤10% at 3 months
• BCR-ABL1 ≤1% at 6 months
• BCR-ABL1 ≤0.1% at 12 months (Major Molecular Response/MMR) 1

Management of Suboptimal Response or Failure

If treatment goals are not met:

• Suboptimal response: Consider dose escalation of current TKI or switch to a different TKI
• Treatment failure: Switch to an alternative TKI based on BCR-ABL1 mutation analysis 2, 1

For patients with the T315I mutation, ponatinib, asciminib, or olverembatinib are the only effective TKIs 3.

Treatment Duration and Discontinuation

• TKI therapy should generally be continued indefinitely in optimal responders 1
• Patients with sustained deep molecular response (MR4 or MR4.5) for at least 2 years after ≥5 years of TKI therapy may be candidates for TKI discontinuation 1

Advanced Disease Management

For accelerated or blast phase CML:

• Higher doses of TKIs
• Consider allogeneic stem cell transplantation 1

Caveat

While allogeneic stem cell transplantation was historically considered the only curative treatment, current guidelines no longer recommend it as initial therapy due to transplant-related mortality. TKIs have transformed CML from a fatal disease to a chronic condition with near-normal life expectancy for most patients 2, 3.