Chronic lymphocytic leukemia: putting new treatment options into perspective

Chronic lymphocytic leukemia (CLL) is a monoclonal B-cell malignancy that afflicts mainly older individuals. Since many patients are diagnosed in the earliest stages, the course of the disease may be indolent and asymptomatic, requiring no therapy. For those who are diagnosed in advanced stages or whose disease becomes symptomatic, treatment is indicated. Advances in identifying prognostic factors, such as cytogenetics, IgHV mutational status, CD38, TP53, and ZAP-70, are helping physicians better predict who is more likely to have progressive disease and thus needs more frequent monitoring. Some of these prognostic factors are also helping to guide therapy choices as they can predict response to treatment and/or duration of response. Recent advances in treatment options have moved beyond traditional management with alkylating agents and purine analogs into regimens combining these two chemotherapy classes with monoclonal antibodies targeting CD20. Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) has become the most effective therapy option to date for CLL. Compared with fludarabine and cyclophosphamide, FCR has shown higher complete response rates and longer progression-free survival. Bendamustine, a unique alkylating agent with purine analog properties, has recently been approved by the FDA for treatment of CLL and provides a new alternative to existing therapies. Initial trials combining bendamustine with rituximab are showing promise for both untreated and relapsed/refractory disease. Other agents recently approved and/or being tested, such as ofatumumab, flavopiridol, and lenalidomide, are demonstrating activity in the relapsed setting.