Martha L Arellano1, Gautam Borthakur2, Mark Berger3, Jill Luer4, Azra Raza5. 1. Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, GA. Electronic address: MARELLA@emory.edu. 2. Department of Leukemia, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX. 3. Department of Clinical Development, Gemin X Pharmaceuticals, Malvern, PA. 4. Department of Medical Affairs, Powered 4 Significance LLC, Annandale, NJ. 5. Division of Hematology/Oncology, Columbia University Medical Center, New York, NY.
Abstract
BACKGROUND: Obatoclax mesylate is a small-molecule Bcl-2 homology domain-3 mimetic that neutralizes antiapoptotic Bcl-2-related proteins. We evaluated obatoclax in untreated MDS patients with anemia/thrombocytopenia. PATIENTS AND METHODS: Twenty-four patients with a bone marrow blast count of ≤ 10% and anemia (hemoglobin level < 10 g/dL) or thrombocytopenia (platelet count < 50 × 10(9)/L) were eligible to receive intravenous obatoclax 60 mg over 24 hours every 2 weeks. RESULTS: Response rate was 8% (2 patients; hematologic improvement). Disease stabilization/response was maintained ≥ 12 weeks in 50% (12 patients). Because the response rate was below a predetermined threshold, the study was terminated. Adverse events (any grade) included euphoric mood (63%; 15 patients), nausea (38%; 9 patients), and diarrhea (25%; 6 patients); Grade 3/4 adverse events included anemia (21%; 5 patients), thrombocytopenia (13%; 3 patients), and pneumonia (13%; 3 patients). CONCLUSIONS: Obatoclax 60 mg every 2 weeks was feasible, but had limited first-line activity in MDS.
BACKGROUND:Obatoclax mesylate is a small-molecule Bcl-2 homology domain-3 mimetic that neutralizes antiapoptotic Bcl-2-related proteins. We evaluated obatoclax in untreated MDSpatients with anemia/thrombocytopenia. PATIENTS AND METHODS: Twenty-four patients with a bone marrow blast count of ≤ 10% and anemia (hemoglobin level < 10 g/dL) or thrombocytopenia (platelet count < 50 × 10(9)/L) were eligible to receive intravenous obatoclax 60 mg over 24 hours every 2 weeks. RESULTS: Response rate was 8% (2 patients; hematologic improvement). Disease stabilization/response was maintained ≥ 12 weeks in 50% (12 patients). Because the response rate was below a predetermined threshold, the study was terminated. Adverse events (any grade) included euphoric mood (63%; 15 patients), nausea (38%; 9 patients), and diarrhea (25%; 6 patients); Grade 3/4 adverse events included anemia (21%; 5 patients), thrombocytopenia (13%; 3 patients), and pneumonia (13%; 3 patients). CONCLUSIONS:Obatoclax 60 mg every 2 weeks was feasible, but had limited first-line activity in MDS.
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