Matt Kalaycio

Many oncologists remember the storied history of homoharringtonine (HHT) and wonder whatever happened to it. HHT showed initial promise for myeloid leukemias, particularly for chronic myelogenous leukemia (CML) where it seemed to induce more cytogenetic remissions than did interferon alpha.1 Unfortunately for HHT investigators, but fortunately for everybody else, these studies coincided with those being done with imatinib. The phenomenal introduction of imatinib contributed to the shelving of HHT in the mid to late 1990s.2 As is often the case, though, imatinib is not perfect. Some patients with CML develop resistance and approximately half of these do so through the acquisition of binding site mutations. One mutation in particular, T315I, rendered patients with CML resistant to all available tyrosine kinase inhibitors (TKI). In the meantime, a semisynthetic version of HHT, omacetaxine mepesuccinate, was developed. With the help of partners in industry, investigators at MD Anderson Cancer Center initiated new studies of omacetaxine in TKI resistant CML patients. Among 62 CML patients with a T315I mutation, complete hematologic response was achieved in 77% with median response duration of 9.1 months.3 Further, cytogenetic response was also achieved in a portion of patients, complete in 16%. These data prompted application for approval by the Food and Drug Administration, but were rejected for lack of a standardized test for T315I mutations. The additional data presented in the Community Translations article on page 194 formed the basis of a second application, this time for an indication in patients with CML resistant to 2 or more TKIs.

Many oncologists remember the storied history of homoharringtonine (HHT) and wonder whatever happened to it. HHT showed initial promise for myeloid leukemias, particularly for chronic myelogenous leukemia (CML) where it seemed to induce more cytogenetic remissions than did interferon alpha.1 Unfortunately for HHT investigators, but fortunately for everybody else, these studies coincided with those being done with imatinib. The phenomenal introduction of imatinib contributed to the shelving of HHT in the mid to late 1990s.2 As is often the case, though, imatinib is not perfect. Some patients with CML develop resistance and approximately half of these do so through the acquisition of binding site mutations. One mutation in particular, T315I, rendered patients with CML resistant to all available tyrosine kinase inhibitors (TKI). In the meantime, a semisynthetic version of HHT, omacetaxine mepesuccinate, was developed. With the help of partners in industry, investigators at MD Anderson Cancer Center initiated new studies of omacetaxine in TKI resistant CML patients. Among 62 CML patients with a T315I mutation, complete hematologic response was achieved in 77% with median response duration of 9.1 months.3 Further, cytogenetic response was also achieved in a portion of patients, complete in 16%. These data prompted application for approval by the Food and Drug Administration, but were rejected for lack of a standardized test for T315I mutations. The additional data presented in the Community Translations article on page 194 formed the basis of a second application, this time for an indication in patients with CML resistant to 2 or more TKIs.

Many oncologists remember the storied history of homoharringtonine (HHT) and wonder whatever happened to it. HHT showed initial promise for myeloid leukemias, particularly for chronic myelogenous leukemia (CML) where it seemed to induce more cytogenetic remissions than did interferon alpha.1 Unfortunately for HHT investigators, but fortunately for everybody else, these studies coincided with those being done with imatinib. The phenomenal introduction of imatinib contributed to the shelving of HHT in the mid to late 1990s.2 As is often the case, though, imatinib is not perfect. Some patients with CML develop resistance and approximately half of these do so through the acquisition of binding site mutations. One mutation in particular, T315I, rendered patients with CML resistant to all available tyrosine kinase inhibitors (TKI). In the meantime, a semisynthetic version of HHT, omacetaxine mepesuccinate, was developed. With the help of partners in industry, investigators at MD Anderson Cancer Center initiated new studies of omacetaxine in TKI resistant CML patients. Among 62 CML patients with a T315I mutation, complete hematologic response was achieved in 77% with median response duration of 9.1 months.3 Further, cytogenetic response was also achieved in a portion of patients, complete in 16%. These data prompted application for approval by the Food and Drug Administration, but were rejected for lack of a standardized test for T315I mutations. The additional data presented in the Community Translations article on page 194 formed the basis of a second application, this time for an indication in patients with CML resistant to 2 or more TKIs.