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CML with Thrombocytosis — RACP Adult Medicine MCQ

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HardHaematologyCML with ThrombocytosisRACP Adult Medicine

A patient with chronic-phase CML loses molecular response on two tyrosine-kinase inhibitors despite confirmed adherence. BCR::ABL1 kinase-domain testing detects T315I, and cardiovascular risk is being assessed. Which treatment principle is correct?

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Correct answer: A — Choose T315I-active ponatinib or asciminib after individual cardiovascular-risk assessment

The best answer is “Choose T315I-active ponatinib or asciminib after individual cardiovascular-risk assessment”. T315I confers resistance to imatinib and most second-generation ATP-site TKIs, whereas ponatinib and appropriate-dose asciminib retain activity. Continuing the ineffective TKI with closer monitoring is not mutation-directed treatment, and hydroxycarbamide controls counts only temporarily. Choosing between active agents requires cardiovascular-risk assessment and consideration of prior intolerance or resistance.

Reference: eviQ, Chronic myeloid leukaemia imatinib: https://www.eviq.org.au/haematology/leukaemias/chronic-myeloid-leukaemia/362-chronic-myeloid-leukaemia-imatinib; eviQ, Chronic myeloid leukaemia ponatinib: https://www.eviq.org.au/haematology/leukaemias/chronic-myeloid-leukaemia/1891-chronic-myeloid-leukaemia-ponatinib