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Abstract：
Treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute leukemia (Ph+ ALL) has been revolutionized with the advent of tyrosine kinase inhibitors (TKIs). Most patients with CML achieve long-term survival similar to individuals without CML due to treatment with TKIs not only in frontline but also in further lines of therapy. The third-generation TKI ponatinib has demonstrated efficacy in patients with refractory CML and Ph+ ALL. Ponatinib is currently the most potent TKI in this setting demonstrating activity against T315I mutant clones. However, ponatinib\'s safety data revealed a dose-dependent, increased risk of serious cardiovascular (CV) events. Guidance is needed to evaluate the benefit-risk profile of TKIs, such as ponatinib, and safety measures to prevent treatment-associated CV events. An expert panel of German hematologists and cardiologists summarize current evidence regarding ponatinib\'s efficacy and CV safety profile. We propose CV management strategies for patients who are candidates for ponatinib.
摘要：
随着酪氨酸激酶抑制剂（TKIs）的出现，慢性粒细胞白血病（CML）和费城染色体阳性急性白血病（PhALL）的治疗发生了革命性的变化。大多数CML患者获得了与没有CML的个体相似的长期生存，这是由于TKI的治疗不仅在前线，而且在进一步的治疗中。第三代TKIponatinib已证明对难治性CML和Ph+ALL患者有效。Ponatinib是目前在这种情况下最有效的TKI，证明了对T315I突变克隆的活性。然而,普纳替尼的安全性数据显示出剂量依赖性，严重心血管（CV）事件的风险增加。需要指导来评估TKIs的收益-风险状况，比如普纳替尼，以及预防治疗相关CV事件的安全措施。德国血液学家和心脏病学家专家小组总结了目前有关普纳替尼疗效和CV安全性的证据。我们提出了针对普纳替尼候选患者的CV管理策略。
