Promises and Challenges of Ponatinib in CML

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Ponatinib is a very potent BCR-ABL inhibitor that is currently approved in the relapse/refractory setting for patients with chronic myeloid leukemia (CML). Ponatinib was initially approved as a treatment for patients with CML in December 2012. However, starting October 31, 2013, ponatinib was temporary removed from the market to address safety concerns. On December 20, the FDA announced the addition of several new safety measures to the ponatinib label, to address the risk of life-threatening blood clots and severe narrowing of blood vessels. By January 2014, ponatinib had returned to the market.

The current FDA approved indication for ponatinib is for the treatment of adult patients with T315I-positive CML or T315I-positive Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Additionally, the drug is approved as a salvage treatment for adult patients with CML or Ph+ ALL.

The EPIC trial was designed to study the efficacy and safety of ponatinib versus imatinib in the frontline setting. Even though patients in the ponatinib arm achieved response quickly, the trial was discontinued early due to the emergence of thrombotic events, Elias Jabbour, MD, explains. As a result, patients on ponatinib were switched to other TKIs. These vascular and thrombotic events prompt the examination of how to optimize therapy in each patient.

Several strategies exist for initiating and titrating ponatinib to reduce the risk of side effects while achieving and maintaining a good response. For example, 45 mg per day is the labeled dose for ponatinib in the relapse setting. Jabbour explains that he instead may use 30 mg per day depending on patient risks, and de-escalate to 15 mg per day once response is achieved. Jessica K. Altman, MD, hopes that with more time, there will be better guidelines and recommendations for how to prescribe ponatinib.