Early results of a phase I trial of oblimersen sodium for relapsed or refractory Waldenstrom's macroglobulinemia

Oblimersen sodium is an antisense oligonucleotide to the first 6 codons of the B-cell leukemia gene 2 (bcl-2) open reading frame. It prevents the expression of the bcl-2 gene product and leads to apoptosis in cells that express Bcl-2. bcl-2 is one of the major apoptosis regulatory gene families and is found in a variety of low-grade B-cell non-Hodgkin's lymphomas. The in vitro use of oblimersen in Waldenstrom's macroglobulinemia (WM) cell line results in enhanced toxicity when exposed to fludarabine, dexamethasone, or rituximab. Oblimersen should also enhance the cytotoxic effect of chemotherapy in WM. Presented herein are early data on the phase I portion of a phase I/II study of oblimersen in WM to identify the maximum tolerated dose and to evaluate response in patients with symptomatic WM.