Among adults in Western countries,
chronic lymphocytic leukemia (CLL) is the most prevalent form of
leukemia. CLL primarily affects the elderly and may be associated with multiple comorbidities. A cure has not been identified, and new treatment options are needed. Expression of Bcl-2
protein is associated with the pathogenesis of CLL and
chemotherapy resistance.
Oblimersen, a Bcl-2 antisense phosphorothioate
oligonucleotide, is being evaluated in patients with CLL and other
cancers; trials through Phase III have been completed. In the setting of relapsed/refractory CLL, single-agent
oblimersen demonstrates modest activity, whereas the addition of
oblimersen to
fludarabine/
cyclophosphamide significantly improves the rate of complete and nodular partial responses; moreover, these responses are durable and associated with clinical benefit.
Oblimersen is more efficacious in relapsed rather than refractory patients. The side effect profile of
oblimersen, alone or in combination with standard
chemotherapy, is favorable compared with currently available
chemotherapies. In the first cycle, an infusion reaction with or without
tumor lysis syndrome is uncommon, and transient
thrombocytopenia is observed.
Catheter-related complications are associated with the need for continuous
intravenous infusion of
oblimersen over several days; other routes of administration are under clinical investigation.
Oblimersen is a promising therapeutic approach for patients with relapsed CLL and should be further evaluated in the front-line setting.