Subcutaneous Omacetaxine Mepesuccinate in Patients With Chronic-Phase Chronic Myeloid Leukemia Previously Treated With 2 or More Tyrosine Kinase Inhibitors Including Imatinib

SUMMARY: Omacetaxine Mepesuccinate (SYNRIBO®) is a first-in-class cephalotaxine and is a semi synthetic purified Homoharringtonine (HHT) compound. HHT is a plant alkaloid derived from Cephalotaxus fortunei, a coniferous bush, also called Japanese Plum Yew. With over 40 years of drug development history since its discovery, SYNRIBO®, unlike Tyrosine Kinase Inhibitors (TKI), is a protein synthesis inhibitor and reduces the levels of multiple Oncoproteins including BCR-ABL, BCL-2, MCL-1 and promotes apoptosis of leukemic stem cells. The following is the pooled data from 2 phase II trials. Treatment population included patients with Chronic Myeloid Leukemia – Chronic Phase (CML-CP), resistant or intolerant to GLEEVEC® (Imatinib) and at least one other TKI such as SPRYCEL® (Dasatinib) and/or TASIGNA® (Nilotinib). All patients had prior treatment with GLEEVEC®, 85% had prior treatment with SPRYCEL® and 59% had prior treatment with TASGNA®. The primary end point was Major Cytogenetic Response (MCyR) and 81 patients with a median age of 59 years were included in this analysis. Treatment consisted of subcutaneous SYNRIBO®, administered at 1.25 mg/m2 twice daily for 14 consecutive days every 4 weeks until response, then for 7 days every 4 weeks as maintenance treatment. The median duration of treatment was 7.5 months. MCyR was noted in 20% of the patients and the median response duration was 17.7 months. Hematologic response was seen in 69% of the patients and the median response duration was 12.2 months. The median failure-free survival was 9.6 months and overall survival was 34 months. The most common grade 3/4 toxicities were cytopenias. The authors concluded that SYNRIBO® has clinical activity in a heavily pretreated population of patients with CML-CP and should therefore be considered for patients with CML-CP with resistance or intolerance to 2 or more TKI’s. By virtue of its mechanism of action, patients with T315I BCR-ABL mutation may potentially benefit from this unique compound. Cortes JE, Nicolini FE, Wetzler M, et al. Clin Lymphoma Myeloma Leuk. 2013;13:584-591.