Newest CML Drug Helps

Chronic myeloid leukemia in resistant cases with ponatinib successful

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

(RxWiki News) The introduction of Gleevec in 2001 to treat chronic myeloid leukemia (CML) marked one of modern oncology's biggest success stories. The treatment has become the model for other cancer drugs.

Unfortunately, not all patients responded to the drug. Now a new drug is showing promise for those resistant to Gleevec.

A team of researchers presented the results from a phase II clinical for ponatib, a specialized medicine for those resistant to Gleevec.The trial results were successful enough to gain approval to advance to phase III testing. 

"Ask your oncologist about new drugs."

“Ponatinib seems to be filling the gap we had for patients who right now have no good treatments left,” said Jorge Cortes, MD, a professor at The University of Texas MD Anderson Cancer Center, stated during a presentation of the original findings from the phase I trial back in December 2010.

Developed by MD Anderson doctors, ponatinib was tested in leukemia patients with a mutation called the Philadephia Chromosome, who had not responded to other targeted leukemia drugs. 

The treatment for CML focuses on targeting a common genetic variation, the Philadelphia chromosome.

The fusion of chromosomes 9 and 22 together is distinctive and well known because the treatments using Gleevec are fairly successful, with around 90 percent of patients showing good results.

While several different drugs exist that specifically target this genetic abnormality in leukemias, the most prominent has been Gleevec.

The trial included a group of patients with a form of leukemia that includes the same chromosomal fusion, acute lymphoblastic leukemia (ALL). While ALL is considered more severe than CML, researchers presented effective results in this group of patients as well.

Nearly 500 patients were enrolled in the trial, and 93 percent of these patients had previously failed at least two currently available targeted therapies.

Out of the patients with chronic-type CML, over half (144 out of 267) had a major response, and the remaining 44 percent had a complete response with ponatinib.

In this trial, out of the 21 patients who had only tried one class of tyrosine kinase inhibitors before beginning ponatinib, 86 percent had a successful response to the therapy.

Even in the most aggressive, acute cases of leukemia with a forbidding prognosis, the blast-phase CML and the ALL patients with the T315I mutation, showed a 33 percent (15 of 46) response to treatment with ponatinib.

The most common side effects reported in the study were a significant drop in levels of platelets in the blood, rash and dry skin in about a third of trial participants.

The most severe side effect was pancreatitis, occurring in six percent of treated patients, and studies show that pancreatitis is the primary dose-limiting side effect for ponatinib.

Patients were followed after the trial for an average of six months, up to 10 months in some of the treatment groups.

“The findings from the global PACE trial of ponatinib confirm its impressive anti-leukemic activity in patients with CML at all stages who are resistant or intolerant to dasatinib or nilotinib, or who have the T315I mutation for which there are no currently available treatments,” stated Dr. Cortes.

“Clinical responses to ponatinib were observed in patients regardless of their mutation status or disease stage,” he added. “Of particular importance, responses to ponatinib appear to be durable, with 93 percent of chronic-phase CML patients projected to remain in major cytogenetic response at one year, clearly highlighting the potency of ponatinib."

The phase III clinical trial of ponatinib is scheduled to begin in the third quarter of 2012. Researchers are optimistic about their results supporting the regulatory filings for marketing approval worldwide.

Study results discussed in conference presentations are considered preliminary until publication in a peer-reviewed journal.

Funding for the study was provided by the manufacturer of ponatinib, ARIAD. Financial disclosures by study authors included existing or previous financial relationships with ARIAD, Bristol-Myers Squibb, ChemGenex, Novartis, Pfizer and Deciphera.

Reviewed by: 
Review Date: 
June 7, 2012
Last Updated:
November 8, 2012