U.S. Food and Drug Administration Approval Summary: Omacetaxine Mepesuccinate as Treatment for Chronic Myeloid Leukemia
[摘要] Chronic myeloid leukemia (CML) results from the neoplastic transformation of a hematopoietic stem cell, affecting all hematopoietic cell lineages. CML is characterized by the presence of the Philadelphia chromosome (a reciprocal translocation between the long arms of chromosomes 9 and 22, leading to formation of a
BCR-ABL gene). The product of this translocation, BCR-ABL protein, is a constitutively active tyrosine kinase that results in the abnormal myelopoiesis in CML [
1]. It is expected that in the U.S., there will be approximately 5,920 new cases of CML and 610 deaths in 2013. In the years between 2000 and 2009, the largest annual decline in death rate from cancer was for CML (8.4%) [
2]. CML has an incidence of approximately 1�?2 cases per 100,000 adults, accounting for approximately 15% of newly diagnosed leukemia in adults [
2]. CML has three phases, representing a disease continuum from chronic phase (CP) to accelerated phase (AP) and to a final blast phase (BP). Transition from CP to AP and BP usually occurs gradually over a period of 1 year or longer, but a blast crisis may occur more rapidly. The disease is usually diagnosed in CP and later progresses to AP and then BP as the number of blasts in the blood and bone marrow increases [
1]. Before the approval of the tyrosine kinase inhibitor (TKI) imatinib, the median survival of patients following a diagnosis of CP CML was 4-6 years. Survival after development of AP was typically <1 year and only a few months after BP. Eight-year follow-up data from the imatinib (IRIS) controlled trial demonstrated a survival rate of 85% for patients treated with imatinib [
3]. Despite these improvements in CML treatment, approximately 30%�?40% of patients receiving imatinib discontinue treatment after 5�?8 years because of drug resistance or toxicity. Five TKIs are now approved for CML: imatinib, nilotinib, dasatinib, bosutinib, and ponatinib.
Table 1 shows the approved TKI drugs that have received an indication for CML.
