A 35-year-old man is diagnosed with Philadelphia chromosome-positive CML in chronic phase. He is started on imatinib 400 mg daily. After 3 months of therapy, BCR-ABL transcript level is 45% (IS). By 12 months, BCR-ABL is 2% (IS). Which term correctly describes the 12-month response and what should be done?
- A Complete haematologic response; continue current dose
- B Optimal molecular response; continue imatinib
- C Warning response (BCR-ABL 1–10% IS at 12 months); consider switch to second-generation TKI ✓
- D Failure; immediate switch to allogeneic stem cell transplant
Correct answer: C. Warning response (BCR-ABL 1–10% IS at 12 months); consider switch to second-generation TKI
Explanation
Per ELN 2020 CML guidelines, the molecular response milestones for imatinib are: at 3 months BCR-ABL ≤10% IS (optimal), at 6 months ≤1% IS (optimal), at 12 months ≤0.1% IS (optimal/MMR). A BCR-ABL of 2% IS at 12 months falls in the 'warning' range (>0.1% to ≤1% IS). Warning response warrants closer monitoring and consideration of switching to a second-generation TKI (nilotinib, dasatinib). A value >1% IS at 12 months would constitute 'failure' requiring mandatory switch. Values >10% IS at any time beyond 3 months define failure.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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