Cardiovascular and Cerebrovascular Complications Following Ponatinib for Philadelphia Chromosome‐Positive Acute Lymphoblastic Leukemia

Ponatinib is a third-generation BCR:ABL1 tyrosine kinase inhibitor used in selected patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), particularly those with T315I mutations, or disease resistant, or those intolerant to prior tyrosine kinase inhibitors. Although effective, ponatinib has been associated with arterial occlusive events. We report a 63-year-old man with Ph+ ALL who, while receving ponatinib, developed a myocardial infarction requiring quadruple coronary artery bypass grafting, followed by symptomatic intracranial arterial stenosis necessitating superficial temporal artery to middle cerebral artery bypass. Despite multiple cardiovascular risk factors, the chronology of progressive coronary and cerebral vascular disease raised suspicion for ponatinib-associated vasculopathy, although causality cannot be established. To our knowledge, this is the first reported case of sequential coronary and cerebral surgical revascularization occurring during ponatinib therapy. This case highlights the importance of careful cardiovascular surveillance, multidisciplinary management, and individualized risk-benefit assessment in patients treated with ponatinib.