What is the role of ponatinib in the treatment of Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL)?

Updated: Feb 20, 2020
  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Ponatinib (Iclusig), a kinase inhibitor, was approved by the US Food and Drug Administration (FDA) in December 2012 for patients with Ph+ ALL, including those with the T315I mutation, who have shown resistance to or intolerance of tyrosine kinase inhibitor therapy. After studies showed that ponatinib poses a high risk for thromboembolic events, its use was restricted to adults with T315I-positive Ph+ ALL, and adults with Ph+ ALL for whom no other tyrosine kinase inhibitor therapy is indicated. [57]

Ph+ ALL is a much more life-threatening disease than chronic myeloid leukemia. Thus, it is possible that the increased potency of ponatinib could justify the toxicity in patients with ALL.  

Sasaki et al studied hyper-CVAD plus ponatinib (47 patients) versus hyper-CVAD plus dasatinib (63 patients) as frontline therapy for patients with Ph+ ALL. [58]  With propensity score matching, the 3-year  event-free survival rates for patients treated with hyper-CVAD plus ponatinib and hyper-CVAD plus dasatinib were 69% and 46%, respectively (P =0.04), and the 3-year OS rates were 83% and 56%, respectively (P =0.03). Patients treated with hyper-CVAD plus ponatinib had significantly higher rates of minimal residual disease negativity by flow cytometry on day 21, complete cytogenetic response at complete response, major molecular response at complete response and at 3 months, and complete molecular response at 3 months.

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