Abstract
Omacetaxine mepesuccinate (Synribo®) is an inhibitor of protein synthesis indicated for the treatment of patients with chronic- or accelerated-phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors. Myelosuppression is the most common and clinically significant toxicity experienced by patients treated with omacetaxine. Here, we further examine the patterns of hematologic toxicity observed in clinical trials and describe the approach to management as well as resolution of events. Omacetaxine-related myelosuppression typically occurs more frequently during induction cycles. In general, the myelosuppression observed with omacetaxine treatment is manageable and reversible, and long-term administration is feasible. Careful monitoring, dose delays and reduction in administration days, and appropriate supportive care are critical for successful management of hematologic toxicity. Concerns regarding myelosuppression, observed with many cancer treatments, should not prevent eligible patients from receiving omacetaxine, particularly CML patients with unsatisfactory responses to multiple lines of prior treatment.
Highlights
Chronic myeloid leukemia (CML) is distinguished by the presence of the BCR-ABL hybrid oncogene and expression of Bcr-Abl oncoprotein, which mediates the activation of signaling pathways leading to leukemogenesis [1]
In a post hoc analysis, data were pooled from two multicenter, open-label, single-arm phase 2 studies (CML-202 and CML-203) in CML patients previously treated with Tyrosine kinase inhibitors (TKIs) [11,13,16]; data were included from all patients with CML-CP and CML-AP who participated in the two trials
A total of 108 patients with CML-CP and 55 patients with CML-AP were treated with subcutaneous omacetaxine at 1.25 mg/m2 twice daily
Summary
Chronic myeloid leukemia (CML) is distinguished by the presence of the BCR-ABL hybrid oncogene and expression of Bcr-Abl oncoprotein, which mediates the activation of signaling pathways leading to leukemogenesis [1]. Tyrosine kinase inhibitors (TKIs) that target BcrAbl represent the mainstay of CML treatment; for patients who develop resistance or intolerance to multiple TKIs, effective therapy remains a major unmetneed. Omacetaxine mepesuccinate (omacetaxine – a semisynthetic form of homoharringtonine) is indicated for adult patients with chronic-phase CML (CML-CP) or accelerated-phase CML (CML-AP) with resistance and/or intolerance to two or more TKIs [2]. Omacetaxine reduced levels of several oncoproteins, including Bcr-Abl and Mcl-1, and induced apoptosis in leukemic cells [7,8,9,10]. Omacetaxine produced durable hematologic and cytogenetic responses in patients with CML-CP and CML-AP, regardless of mutational status [11,12,13,14,15]
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