Multicenter open label study of subcutaneous (SC) omacetaxine (OMA) in imatinib
(IM)-resistant chronic myeloid leukemia (CML) patients (Pts) with the T315I mutation.
Sub-category: Leukemia
Category: Leukemia, Myelodysplasia, and Transplantation
Meeting: 2008 ASCO Annual Meeting
Abstract No: 7021
Citation: J Clin Oncol 26: 2008 (May 20 suppl; abstr 7021)
Author(s): A. Benichou, H. J. Khoury, S. Corm, F. E. Nicolini, A. R. Craig, E. Humphriss, J. E. Cortes
Abstract: Background: Omacetaxine mepesuccinate (semi-synthetic homoharringtonine, HHT) is clinically active
against Ph+ CML, with a mechanism of action independent of tyrosine kinase (TK) inhibition. Currently available TK
inhibitors have not demonstrated activity in CML patients with the T315I mutation. We are evaluating the
safety/efficacy of SC OMA in Pts with IM-resistant T315I+ Ph+ CML. Methods: Eligible Pts- adult T315I+ CML
following imatinib failure or intolerance. Induction schedule: 1.25 mg/m2 SC twice daily (BID) for 14 days every 28
days until complete hematologic response (CHR) or hematologic improvement. Maintenance schedule: 1.25 mg/m2
BID for 7 days every 28 days, for up to 24 mos. Results: To date, 29 Pts have been enrolled, 17 in chronic phase (CP),
6 in accelerated phase (AP) and 6 in myeloid blast phase (BP). Median age: 58 yrs (19-83), median disease duration: 58
mo. (9-287). Overall hematologic response rate: CP 64%, AP 100%, and BP 34%, with 45% CHR in CP patients.
Overall cytogenetic response rate (CyR): CP 27% and AP 25%, with 2 complete CyR in CP and 1 minor CyR in AP.
Median time to response 2 mo. (1-5), median duration of response 4 mo. (1-13+). Incidence of grade 3/4 events:
thrombocytopenia 52%, anemia 43%, neutropenia 43%, febrile neutropenia 22% and diarrhea 17%. Grade 1-2 local
injection site pain or erythema in 23% and 13% of cases, respectively. T315I transcript levels are no longer detectable
in 50% (7/14) of Pts. Conclusions: OMA therapy in T315I+ IM-resistant CML Pts has been well tolerated and resulted
in durable CHRs and cytogenetic responses.