Treatment of relapsed or refractory chronic lymphocytic leukemia

Recent advances in the treatment of chronic lymphocytic leukemia (CLL) have moved beyond the traditional use of alkylating agents and purine analogs into regimens combining these two chemotherapy classes with monoclonal antibodies.

This article reviews treatments options for patients with relapsed or refractory CLL.

Several studies have investigated novel agents in treating patients with 17p deletion, TP53 mutation, and fludarabine-refractory CLL, as well as patients with suboptimal response to intense treatment. These investigational agents include rituximab, alemtuzumab, ofatumumab, bendamustine, high-dose methylprednisolone, lenalidomide, lumiliximab, cyclin-dependent kinase inhibitors, small modular immunopharmaceuticals, Bcl-2 inhibitors, and histone deacetylase inhibitors. While these newer drugs and combination therapies have shown promise as treatment options for CLL, additional studies are needed to determine the immunosuppression, toxicities, and infections associated with their use.

Despite improvement in initial overall response rates, most patients relapse and require further treatment. CLL remains incurable with standard therapies due to development of disease refractoriness. As such, novel approaches such as those noted above warrant continued research to improve outcomes for patients with CLL.