Attacking Leukemia Resistance

Resistant chronic myeloid leukemia responds to investigational drug ponatinib

/ Author:  / Reviewed by: Joseph V. Madia, MD

(RxWiki News) Chronic myeloid leukemia (CML) is a tricky cancer because it can respond well to initial therapy, but then that drug sometimes stops working. The same thing can happen when different – second-line – drugs are used. The reason for this is that the disease tends to keep changing or mutating.

An investigational drug called ponatinib, currently being evaluated in a phase I trial, has shown its ability to overcome a CML mutation that’s never been touched by other medications. The T315I mutation has been one of the biggest challenges in providing long-term disease stability for CML patients.

People with another form of leukemia and those who had no CML mutations also responded well to ponatinib.

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The lead investigator of this multi-center trial is investigator Jorge Cortes, MD, professor in The University of Texas MD Anderson Department of Leukemia.

“Ponatinib is a promising new treatment for patients who have run out of options, and its activity against other resistant mutations and in patients with no known mutations suggests a broad range of efficacy for this drug,” Dr. Cortes said in a press release.

Chronic myeloid leukemia develops when parts of two chromosomes change places, resulting in a mutated gene product called the Philadelphia chromosome. It is seen in CML and in Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL).

A total of 81 patients with relapsed or resistant (unresponsive) blood cancers are participating in the phase I trial, which establishes the safety of the drug being investigated. Of this group, 60 patients had CML and five had ALL.

About 20 percent of CML patients have the T315I mutation, which blocks access to the protein that other currently available drugs treat.

The 12 patients in the study with this mutation had what’s called a complete hematologic response, meaning after being treated with ponatinib, no CML cells were found in the blood. Of these patients, 9 patients had no cells in the marrow, which is known as a complete cytogenic response.

The investigational drug also produced excellent results in patients who had different types of mutations – other than T3151 – or no mutations at all.

Of the 65 patients with resistant CML at various stages, and those with ALL, ponatinib produced a complete cytogenetic response in 67 percent of participants and 46 percent of patients who had no detectable mutations.

Ponatinib is currently under accelerated review by the US Food and Drug Administration. Ariad Pharmaceuticals applied for the review of ponatinib for patients with resistant or intolerant CML or Philadelphia chromosome-positive ALL.

Other medications currently approved to treat CML include: Gleevec (imatinib); Sprycel (dasatinib) and Tasigna (nilotinib). Bosulif (bosulitinib) and Synribo (omacetraxine) have recently been approved to treat resistant CML

Results from this study are reported in the November 28 issue of the New England Journal of Medicine.

This study was funded by Ariad Pharmaceuticals. Dr. Cortes has received research support from and has consulted for Ariad.

Reviewed by: 
Review Date: 
November 28, 2012
Last Updated:
November 29, 2012