Investigational Omacetaxine Appears to Overcome Tyrosine Kinase-Resistant Chronic Myeloid Leukaemia: Presented at ASH
By Ed Susman
NEW ORLEANS -- December 7, 2009 -- Omacetaxine, a drug long used in China for the treatment of leukaemia, might be able to overcome a frequent mutation that renders chronic myeloid leukaemia (CML) resistant to tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, and nitolinib.
According to Jorge Cortes, MD, University of Texas, M. D. Anderson Cancer Center, Houston, Texas, omacetaxine works differently than through the tyrosine kinase pathway to attack the Bcr-Abl mutation known as T315I.
However, treatment with omacetaxine, “represents a new potential therapy for patients with T315I-positive chronic myeloid leukaemia,” said Dr. Cortes here at the American Society of Hematology (ASH) 51st Annual Meeting and Exposition on December 5.
For the study, 81 patients with confirmed T315I-positive mutations who were progressing on imatinib or other TKIs were given subcutaneous omacetaxine 1.25 mg/m2 twice daily for 14 days every 28 days as induction therapy until haematologic response. For maintenance therapy, patients were dosed twice daily for 7 days every 28 days.
Although the mean follow-up time was short (median, 6.4 months), Dr. Cortes said 86% of the 49 chronic-phase patients in the study who no longer were controlling their disease with imatinib had achieved a complete haematological response.
About 27% of patients had achieved a major cytogenetic response, defined as absence of Bcr-Abl mutation in at least 35% of cells and ~18% of the patients had achieved a complete cytogenetic response.
The median age of the patients in the study was 58 years (range, 19-83 y) and their median time diagnosed with CML was 54 months. Imatinib failed to control the disease in all the patients and 79% had failed >=2 prior TKIs.
Dr. 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 TKIs in the face of a T315I mutation.
“What is encouraging is that we are seeing that patients are able to respond to this therapy,” he said during a press briefing. “It is self-administered subcutaneously and we have seen that it is very well tolerated.”
Treatment delays occurred in ~50% of patients and the primary causes of delay were thrombocytopenia, neutropenia, and pancytopenia.
[Presentation title: Safety and Efficacy of Subcutaneous-Administered Omacetaxine Mepesuccinate in Imatinib-Resistant Chronic Myeloid Leukemia (CML) Patients Who Harbor the Bcr- Abl T315I Mutation - Results of An Ongoing Multicenter Phase 2/3 Study. Abstract 644]
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