Post hoc analysis of sustained efficacy/tolerability of ≥12 cycles of omacetaxine mepesuccinate in chronic myeloid leukemia (CML).

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7066 Background: Subcutaneous omacetaxine mepesuccinate (OMA), a first-in-class cephalotaxine, inhibits protein synthesis independent of Bcr-Abl signaling. It showed clinical activity in 2 phase II, open-label CML trials, 1 in patients with a T315I Bcr-Abl mutation failing imatinib, and 1 in patients failing ≥2 tyrosine kinase inhibitors (TKIs). Methods: This post hoc analysis pooled patients with chronic phase (CP) or accelerated phase (AP) from the 2 trials. 28-day cycles of OMA 1.25 mg/m2BID were given ≤14 days for induction, ≤7 days as maintenance with dose delay/change as needed. Primary endpoints were major cytogenetic response (MCyR) for CP and complete hematologic response (CHR) for AP. Adverse events (AEs) were assessed. Results: Of 108 CP and 51 AP patients from the 2 trials, 31 (29%) CP and 7 (14%) AP patients received ≥12 cycles (Table). At baseline in the ≥12-cycle groups, most CP (median age 59 y) and AP patients (median age 67 y) had received hydroxyurea (17/31, 4/7) and ≥2 TKIs (22/31, 5/7), were not in CHR (22/31, 5/7), and were T315I positive (23/31, 3/7). As of March 31, 2012, 9 CP and 2 AP patients continued OMA treatment. Overall, mean days dosed per cycle were 6.1 for CP, 9.7 for AP; 5.3 and 8.9 at cycle 12. Grade 3/4 AEs occurred in 35/38 patients in this post hoc analysis, most in early cycles; 15/31 CP, 2/7 AP had grade ≥3 AEs first occurring at ≥12 cycles. Across all cycles, most common grade ≥3 AEs were thrombocytopenia (24/31 CP, 5/7 AP), anemia (16/31, 7/7), and neutropenia (17/31, 3/7).Nine patients receiving ≥12 cycles (5/31, 4/7) discontinued, most commonly due to disease progression (n=2). Conclusions: In this post hoc analysis of heavily pretreated CML-CP and CML-AP patients who had failed prior TKI therapy, efficacy was often durable for those who received OMA for ≥12 cycles. Most grade 3/4 AEs were hematologic and declined with time. Support: Teva BPP R and D, Inc. Clinical trial information: NCT00375219, NCT00462943.