A Phase II, Multicenter, Open-Label Study of Obatoclax Mesylate in Patients With Previously Untreated Myelodysplastic Syndromes With Anemia or Thrombocytopenia

BackgroundObatoclax 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 MethodsTwenty-four patients with a bone marrow blast count of ≤ 10% and anemia (hemoglobin level < 10 g/dL) or thrombocytopenia (platelet count < 50 × 109/L) were eligible to receive intravenous obatoclax 60 mg over 24 hours every 2 weeks.ResultsResponse 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).ConclusionsObatoclax 60 mg every 2 weeks was feasible, but had limited first-line activity in MDS.