Department of Haematology and Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany,
Department of Cardiology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
Acta Haematol. 2020;143(3):217-231. doi: 10.1159/000501927. Epub 2019 Oct 7.
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.
酪氨酸激酶抑制剂（TKI）的出现彻底改变了慢性髓性白血病（CML）和费城染色体阳性急性白血病（Ph+ ALL）的治疗方法。由于 TKI 的治疗不仅在一线治疗中，而且在进一步的治疗线中，大多数 CML 患者的长期生存与无 CML 的个体相似。第三代 TKI 帕纳替尼已在难治性 CML 和 Ph+ ALL 患者中显示出疗效。帕纳替尼是目前该治疗环境中最有效的 TKI，对 T315I 突变克隆具有活性。然而，帕纳替尼的安全性数据显示，严重心血管（CV）事件的风险与剂量相关增加。需要指导来评估 TKI（如帕纳替尼）的获益-风险特征，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的专家小组总结了关于帕纳替尼疗效和 CV 安全性概况的现有证据。我们为适合使用帕纳替尼的患者提出了 CV 管理策略。
