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.

中文翻译：

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帕纳替尼——历史发展、现状和未来研究回顾

Ponatinib 是第三代 BCR::ABL1 酪氨酸激酶抑制剂 (TKI)，对费城染色体 (Ph) 阳性白血病（包括对第一代和第二代 TKI 耐药的 T315I 突变疾病）具有高效力。帕纳替尼被批准用于治疗 T315I 突变的慢性粒细胞白血病 (CML)、对 ≥2 种既往 TKI 耐药/不耐受的 CML、晚期 CML 和 Ph 阳性急性淋巴细胞白血病 (ALL)（没有其他 TKI 适应症），以及 T315I 突变的 CML 和Ph 阳性 ALL。慢性期 CML (CP-CML) 中基于反应的帕纳替尼剂量可改善治疗耐受性并降低毒性风险，包括心血管风险。与之前的 TKI 相比，基于 Ponatinib 的治疗在一线 Ph 阳性 ALL 中也取得了显着更好的结果，并且正在成为这种情况下的新护理标准。随着第三代 TKI 及其合理组合的临床开发的进展，我们预计 CML 和 Ph 阳性 ALL 的治疗将发生进一步的变革。