imatinib + ponatinib

imatinib + ponatinib refers to the concurrent or sequential use of two oral BCR::ABL1 tyrosine kinase inhibitors—first‑generation imatinib and third‑generation ponatinib—as a combination therapeutic strategy in Philadelphia chromosome–positive malignancies, primarily chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (Ph+ ALL). Imatinib selectively inhibits BCR::ABL1 and additional kinases such as KIT and PDGF receptors, while ponatinib is a pan‑BCR::ABL1 inhibitor rationally designed to retain activity against resistant mutants including T315I and other single‑mutation variants. In clinical practice and research, the two agents are more commonly compared head‑to‑head rather than co‑administered, with ponatinib plus chemotherapy showing superior minimal residual disease–negative remission rates versus imatinib plus chemotherapy in newly diagnosed Ph+ ALL; however, combined or sequential TKI strategies may be explored for complex resistance patterns or in investigational settings.