A 50-year-old man presents with splenomegaly, WBC 120,000/µL with a left shift, basophilia, and Philadelphia chromosome positive (BCR-ABL1). He is started on imatinib. After 12 months, PCR for BCR-ABL1 remains detectable at 1% IS. What is the NEXT best step?
- A Continue imatinib; response is adequate at 12 months
- B Add hydroxyurea to imatinib
- C Switch to a 2nd-generation TKI (dasatinib or nilotinib) and perform BCR-ABL kinase domain mutation testing ✓
- D Proceed directly to allogeneic stem cell transplantation
Correct answer: C. Switch to a 2nd-generation TKI (dasatinib or nilotinib) and perform BCR-ABL kinase domain mutation testing
Explanation
By ELN 2020 response milestones for CML on TKI therapy, an optimal response at 12 months requires BCR-ABL1 (IS) ≤0.1% (major molecular response, MMR). BCR-ABL1 of 1% IS at 12 months is a warning response. The recommended action is BCR-ABL kinase domain mutation testing (to detect T315I 'gatekeeper' or other resistance mutations) and switching to a more potent 2nd-generation TKI (dasatinib, nilotinib, or bosutinib). T315I mutation requires ponatinib (3rd-generation). Allogeneic SCT is reserved for blast crisis or failure of multiple TKIs.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.