Therapy of elderly/comorbid patients with chronic lymphocytic leukemia

Treatment of chronic lymphocytic leukemia (CLL) has recently undergone revolutionary changes. Two large randomized trials demonstrated superiority of chemoimmunotherapy combining fludarabine and cyclophosphamide with monoclonal anti-CD20 antibody rituximab (FCR) over fludarabine and cyclophosphamide (FC) alone in first line and relapse; this lead to establishment of FCR regimen as new gold standard in younger and physically fit patients. However, elderly and/or comorbid patients may not tolerate such aggressive approach due to high risk of unacceptable toxicity. To date, no randomized trials in this patient population have improved therapeutic results over chlorambucil; therefore, this agent remains the backbone of treatment against which the new protocols should be tested. Indeed, several currently running large trials investigate whether addition of an anti-CD20 monoclonal antibody (rituximab, obinutuzumab, ofatumumab) to chlorambucil yields better results. Performance status, biological age and number/severity of comorbid conditions should be incorporated into decision-making process with regard to intensity of treatment. Other emerging treatment alternatives for this patient population include fludarabine-based regimens in attenuated doses as well as protocols containing bendamustine or lenalidomide. Highdose steroids combined with rituximab might be a promising in relapsed/refractory CLL but infectious toxicity is serious. Finally, ofatumumab has been recently approved for the treatment of fludarabine and alemtuzumab-refractory patients. This article provides an overview of the current and future possibilities in the treatment of elderly and comorbid patients with CLL.