For subcutaneous use in the treatment of adult patients with chronic or accelerated phase chronic myeloid leukemia (CML) with resistance and/or intolerance to two or more tyrosine kinase inhibitors.
Trade name Synribo.
Mechanisms of action include the inhibition of protein synthesis and activity independent of the BCR/ABL binding.
Reduces levels of the BCR-ABL oncoprotein and Mcl-1 and it’s activity.
Its activity is not affected by the presence of BCR-ABL mutations.
The efficacy population includes patients with CML acute and chronic phase who had received two or more prior TKIs.
Efficacy is modest with 18-20% major cytogenic responses in patients in chronic phase CML but not in patients with accelerator phase disease.
Major cytogenetic response (MCyR) was achieved in 18.4% of patients with CML-chronic phase, with a median response duration 12.5 months, and major hematologic response in 14.3% of patients with CML-acute phase with a median response duration 4.7 months.
Trials have not shown increased survival with this agent.
Most common adverse reactions in the combined safety population of patients with CML-CP and AP included thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection and lymphopenia.
Myelosuppression may be severe and fatal.
Can induce glucose intolerance, so should be avoided in patients with poorly controlled diabetes mellitus until good glycemic control has been established.
Can cause fetal harm when administered to a pregnant woman.
Serious adverse reactions with greater than 5% frequency in chronic phase CML patients: bone marrow failure, thrombocytopenia, febrile neutropenia, and infections.
The recommended dose and schedule for omacetaxine mepesuccinate is 1.25 mg/m2 subcutaneous injection twice daily for 14 days of a 28 day cycle for the induction phase and 1.25mg/m2 subcutaneous injection twice daily for 7 days of a 28 day cycle for maintenance.