A 35-year-old woman with chronic myeloid leukaemia (CML) in chronic phase on imatinib 400 mg/day achieves complete cytogenetic response at 12 months but fails to achieve major molecular response (BCR-ABL IS >0.1%) at 18 months. What is the recommended management per ELN 2020 guidelines?
- A Switch to a second-generation TKI (dasatinib or nilotinib) after ABL kinase domain mutation testing ✓
- B Increase imatinib to 600–800 mg/day
- C Add interferon-alfa to current imatinib
- D Proceed to allogeneic stem cell transplantation immediately
Correct answer: A. Switch to a second-generation TKI (dasatinib or nilotinib) after ABL kinase domain mutation testing
Explanation
ELN 2020 defines failure to achieve MMR (BCR-ABL IS ≤0.1%) by 18 months as treatment failure on imatinib, warranting switch to a second-generation TKI. Before switching, ABL kinase domain mutation analysis should guide which 2G-TKI to select — for example, T315I mutation requires ponatinib (third-generation), while E255K/V favours dasatinib over nilotinib. Imatinib dose escalation is not recommended for failure (only for suboptimal response). SCT is reserved for accelerated/blast phase or multiple TKI failures.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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