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

Curative therapies are lacking for older patients with myelodysplastic Syndrome (MDS). In this small phase II study, the B-cell lymphoma 2 (Bcl-2) inhibitor obatoclax (60 mg over 24 hours every 2 weeks) was feasible and relatively well tolerated, 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 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 x 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.