帕纳替尼
医学
达沙替尼
髓系白血病
费城染色体
伊马替尼
内科学
肿瘤科
药理学
生物
遗传学
染色体易位
基因
作者
Hagop M. Kantarjian,Helen T. Chifotides,Fadi Haddad,Nicholas J. Short,Sanam Loghavi,Elias Jabbour
摘要
Abstract Ponatinib is a third‐generation BCR::ABL1 tyrosine kinase inhibitor (TKI) with high potency against Philadelphia chromosome (Ph)‐positive leukemias, including T315I‐mutated disease, which is resistant to first‐ and second‐generation TKIs. Ponatinib was approved for T315I‐mutated chronic myeloid leukemia (CML), CML resistant/intolerant to ≥2 prior TKIs, advanced phase CML and Ph‐positive acute lymphoblastic leukemia (ALL) where no other TKIs are indicated, and T315I‐mutated CML and Ph‐positive ALL. The response‐based dosing of ponatinib in chronic phase CML (CP‐CML) improved treatment tolerance and reduced the risk of toxicities, including cardiovascular risks. Ponatinib‐based therapy also resulted in significantly better outcomes in frontline Ph‐positive ALL compared with prior TKIs and is becoming a new standard of care in this setting. As the clinical development of third‐generation TKIs and their rational combinations progresses, we envision further transformative changes in the treatment of CML and Ph‐positive ALL.
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