Incidence and management of myelosuppression in patients with chronic- and accelerated-phase chronic myeloid leukemia treated with omacetaxine mepesuccinate

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.

Plant Secondary Metabolites as Anticancer Agents: Successes in Clinical Trials and Therapeutic Application

“…Although homoharringtonine treatment may result in some hematologic toxicity such as myelosuppression, this should not prevent the use of this drug, once the benefits exceed the damage and the latter can be limited mainly by adequate dose adjustment and patient training for symptoms [ 82 ]. All these data show a large number of scenarios where homoharringtonine use is applied and suggest many others where it can receive approval in the near future, showing that its long history in cancer therapy is far from over.…”

A phase II study of omacetaxine mepesuccinate for patients with higher‐risk myelodysplastic syndrome and chronic myelomonocytic leukemia after failure of hypomethylating agents

“…One possibility is that this incomplete count recovery may in part be explained by the myelosuppressive effects of OM, as grade ≥ 3 thrombocytopenia, neutropenia, or anemia were reported in 68%, 46%, and 36% of patients, respectively, who were treated with OM for chronic phase CML. 21 However, the doses of OM used in this study were significantly lower than those used in CML (ie, 3-day regimen vs 14-day induction and 7-day consolidation regimen), and therefore the myelosuppressive effects of OM are expected to be less.…”

Haematological adverse events associated with tyrosine kinase inhibitors in chronic myeloid leukaemia: A network meta‐analysis

“…Subgroup analysis for second-and third-line TKIs could not be carried out, despite evidence reporting that haematological toxicity occurs in a higher proportion of patients using second-and third-line TKIs due to intolerance or resistance to prior TKIs. 1,3,80 Furthermore, studies including patients in the accelerated and blast phases of CML, which are phases related to treatment resistance-which is considered as a decisive factor in the therapeutic selection-were not found.…”