A 45-year-old man with CML on imatinib for 18 months achieves complete cytogenetic response but fails to achieve a major molecular response (MMR, BCR-ABL1 IS >0.1%). Mutation analysis shows a T315I mutation in BCR-ABL1. Which TKI is appropriate?
- A Dasatinib
- B Nilotinib
- C Ponatinib (AP24534) ✓
- D Bosutinib
Correct answer: C. Ponatinib (AP24534)
Explanation
T315I is the 'gatekeeper' mutation that confers resistance to ALL first- and second-generation BCR-ABL TKIs (imatinib, dasatinib, nilotinib, bosutinib) because the threonine-to-isoleucine substitution abolishes the hydrogen bond critical for drug binding. Ponatinib (a third-generation TKI) and asciminib (a STAMP inhibitor targeting the myristoyl pocket) are the only approved agents with activity against T315I. Allogenic stem cell transplantation may also be considered in accelerated or blast phase.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.