Abstract

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.

Keywords: Chronic lymphocytic leukemia, comorbidity, health-related quality of life, creatinine clearance, elderly patients, low-dose fludarabine, comprehensive geriatric assessment, randomized trials, FCR regimen, alemtuzumab-refractory patients