Pooled safety analysis of omacetaxine mepesuccinate in patients with chronic myeloid leukemia (CML) resistant to tyrosine-kinase inhibitors (TKIs).

6604 Background: Subcutaneous omacetaxine mepesuccinate (“omacetaxine”) is a reversible, transient inhibitor of protein elongation that does not depend on BCR-ABL signaling. It showed significant clinical activity in two phase 2, open-label, multicenter studies of patients with CML who were resistant/intolerant to prior TKI therapy. However, omacetaxine tolerability data across the 3 phases of CML are limited. Methods: Safety data were pooled from all patients in the 2 studies plus a small pilot study. Omacetaxine 1.25 mg/m2 was given subcutaneously twice daily: ≤14 successive days per 28-day cycle for induction, ≤7 days/cycle as maintenance. Days of dosing could be adjusted and recombinant growth factors given, as clinically indicated. Results: Of 207 pooled patients (median age, 57 years), 108 were in chronic (CP), 55 in accelerated (AP), and 44 in blast phase (BP). Median treatment was 4 cycles (range, 1–41). On study, 80% of patients had ≥1 hematologic adverse event (AE), 60% had a serious AE (SAE), 3...