Michael J. Mauro, MD, from the Memorial Sloan Kettering Cancer Center, New York, NY, discusses the latest follow-up results from a Phase I trial of ponatinib in chronic myeloid leukemia (CML) patients, with a focus on chronic-phase patients (NCT00660920) at the American Society of Hematology (ASH) Congress 2016 in San Diego, CA. Response and time to response in those patients in the chronic phase of CML showed that major and complete cytogenetic and molecular remission was achieved in the majority of heavily pre-treated patients who had previously received 3 or 4 lines of therapy. Prof. Mauro explains that those patients in this Phase I trial who were exposed to lower doses of ponatinib had good outcomes compared to those receiving higher doses, and argues that this is encouraging as lower doses of ponatinib are now being investigated. He points out that toxicity rates, such as arterial occlusive events and venous thromboembolisms, were quite high, and argues that these to be able to be better scrutinized in order to elucidate the mechanism of action and reduce the risk of these events. While few patients discontinued the use of ponatinib due to these adverse events, these need to be better understood to optimize the risk-benefit ratio. Prof. Mauro argues that ponatinib is a good drug for highly resistant CML patients, which can be used in the appropriate population once the dose is optimized and toxicity understood.