However, the efficacy seen with ponatinib comes at the price of toxicity, which can be severe if not addressed appropriately, Goldberg notes. In October 2013, the FDA requested that the manufacturer of ponatinib, Ariad Pharmaceuticals, suspend marketing in order to address a higher than expected number of serious vascular occlusion events. In December 2013, new safety measures were put into place, including a risk evaluation and mitigation strategy (REMS). Moreover, the label for ponatinib was narrowed specifically to patients with T315I-positive disease.

In clinical trials, ponatinib was associated with arterial and venous thrombosis and occlusions in at least 27% of patients treated with the drug, according to the FDA. Given this level of cardiovascular events, Goldberg advises careful consideration before utilizing ponatinib, including a careful conversation with the patient weighing the pros and cons.

The third-generation TKI ponatinib has demonstrated efficacy in patients with chronic myeloid leukemia (CML), specifically those with high-risk mutations such as T315I, notes Stuart L. Goldberg, MD. Based on this efficacy in a hard-to-treat population, the FDA granted an accelerated approval to ponatinib in December 2012 as a treatment for patients with CML who were resistant or intolerant to prior TKI therapy.