A 52-year-old man with newly diagnosed chronic myeloid leukemia (CML) in chronic phase presents to the oncology clinic. BCR-ABL mutation analysis is negative. He has no contraindications to tyrosine kinase inhibitor (TKI) therapy. What is the most appropriate next step in management?

Explanation

## First-Line Management of CML in Chronic Phase **Key Point:** Tyrosine kinase inhibitors (TKIs) are the standard first-line therapy for newly diagnosed CML in chronic phase, regardless of BCR-ABL mutation status at presentation. ### Rationale for Imatinib Mesylate **High-Yield:** Imatinib at 400 mg once daily is the preferred initial TKI for chronic phase CML because: - It is the most extensively studied first-generation TKI - Achieves complete hematologic response in >95% of chronic phase patients - Well-tolerated with manageable side effect profile - Cost-effective compared to second-generation TKIs ### Monitoring Strategy **Clinical Pearl:** BCR-ABL transcript monitoring (quantitative RT-PCR) at 3 months is critical to assess: - Achievement of major molecular response (MMR: ≥3-log reduction) - Early warning of TKI resistance or intolerance - Guide for dose escalation or TKI switch if needed ### Why Imatinib Over Second-Generation TKIs? While dasatinib and nilotinib are also approved for first-line use, imatinib remains standard because: - Equivalent efficacy in chronic phase disease - Lower cost and toxicity profile - Reserve second-generation TKIs for imatinib resistance/intolerance **Mnemonic: FIRST-LINE CML THERAPY — "I DASH Nil"** - **I**matinib (first choice, chronic phase) - **DASH**atinib (second-gen, faster response) - **Nil**otinib (second-gen, faster response) [cite:Harrison 21e Ch 104]