Action Points
- Explain to interested patients that this report describes preliminary findings about an investigational drug that is not FDA approved and is not available for clinical use.
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.
NEW ORLEANS -- Promising preliminary findings from a small study suggest a possible treatment for imatinib (Gleevec)-resistant chronic myeloid leukemia (CML), researchers reported here.
Researchers had already identified the the cause of resistance -- the T3151 mutation -- and now they may have a fix for the problem that has become the Achilles' heel of CML therapy, Jorge Cortes, MD, professor of medicine at the University of Texas, M.D. Anderson Cancer Center.
The investigational drug, omacetaxine, being developed by ChemGenex Pharmaceuticals Limited, based in Menlo Park, Calif., and Melbourne, Australia, "represents a new potential therapy for patients with T315I-positive chronic myeloid leukemia," Cortes said at the American Society of Hematology meeting.
That hopeful note emerged from a study designed to evaluate the safety and efficacy of subcutaneously administered omacetaxine in patients with imatinib resistant T315I Philadelphia chromosome-positive chromin myeloid leukemia. Patients were given 1.25 mg/m2subcutaneous omacetaxine twice daily for 14 days every 28 days until hematologic response for induction therapy.
For maintenance therapy, patients were dosed twice daily for seven days every 28 days.
Although the mean follow-up time was short, Cortes said the early results revealed a number of promising findings including:
- After a mean of nine months follow-up, 86% of the 49 chronic phase patients in the study who no longer were controlling their disease with imatinib had achieved a complete hematological response.
- About 27% of patients had achieved a major cytogenetic response, defined as absence of Bcr-Abl mutation in at least 35% of cells.
- Roughly 18% of the patients had achieved a complete cytogenetic response -- all the cells appear to have lost the Bcr-Abl mutation.
The median age of the patients in the study was 58 years, and ranged from 19 to 83. Their median time diagnosed with chronic myeloid leukemia was 54 months. Imatinib failed to control the disease in all the patients; 79% had failed two or more prior tyrosine kinase inhibitors. The presence of baseline T315I mutation was confirmed in all patients.
Cortes said the study did not have a control arm because there is no established treatment for patients whose disease has progressed despite use of imatinib and other tyrosine kinase inhibitors in the face of the T315I mutation.
He explained that omacetaxine, which is not approved in the U.S. or Europe, has been used to treat leukemia in China for many years and it appeared to work against the mutation in the laboratory.
"What is encouraging is that we are seeing that patients are able to respond to this therapy," he said at a press briefing here. "It is self-administered subcutaneously and we have seen that it is very well tolerated."
"One can draw a parallel between the acquisition of antibiotic resistance in bacterial infections and the development of drug resistance due to a mutation in this case which blocks the binding of drugs like imatinib to the active site in chronic myeloid leukemia cells," said Richard Larson, MD, professor of medicine at the University of Chicago, who acted as a moderator at the press briefing.
He said omacetaxine and other drugs in the development pipeline will be important in treating even small groups of patients.
"It is fair to say that therapeutic breakthroughs never occur quickly enough to help everyone. The good news is there are a lot of new agents in the pipeline. The challenge is that each subset of disease becomes smaller," Larson said.
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