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Saussele, Susanne; Haverkamp, Wilhelm; Lang, Fabian; Koschmieder, Steffen; Kiani, Alexander; Jentsch-Ullrich, Kathleen; Stegelmann, Frank; Pfeifer, Heike; La Rosee, Paul; Goekbuget, Nicola; Rieger, Christina; Waller, Cornelius F.; Franke, Georg-Nikolaus; le Coutre, Philipp; Kirchmair, Rudolf and Junghanss, Christian (2020): Ponatinib in the Treatment of Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Leukemia: Recommendations of a German Expert Consensus Panel with Focus on Cardiovascular Management. In: Acta Haematologica, Vol. 143, No. 3: pp. 217-231

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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.

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