Treatment of patients with fludarabine-refractory chronic lymphocytic leukemia: need for new treatment options.

Fludarabine-refractory chronic lymphocytic leukemia is associated with poor survival rates. Chemoimmunotherapy combinations that include purine analogs, alkylating agents, and monoclonal antibodies have shown the highest response rates to date. Intensive treatment approaches can be associated with poor tolerability that is often characterized by deteriorating immune functions and high infection rates. Treatment with some monoclonal antibodies is often complicated by infusion-related adverse events and increased risk of infections. Several novel agents are currently being investigated for this difficult-to-treat patient population. Ofatumumab is an anti-CD20 monoclonal antibody that targets a different epitope from the one targeted by rituximab and, it has shown promising antileukemia activity. Lenalidomide is an immunomodulatory agent that has shown promising activity in patients with fludarabine-refractory chronic lymphocytic leukemia, many of whom had poor prognostic features and bulky disease. Encouraging results have been observed with each of these agents individually. However, given the diverse mechanisms governing CLL pathogenesis and disease progression, ongoing clinical trials combinations of these agents may improve clinical outcomes for this patient population.