Abstract
Treatment of chronic lymphocytic leukemia (CLL) has recently undergone several major changes. Most importantly, large randomized trials (CLL-8 in first line and REACH in relapse) clearly demonstrated superiority of chemoimmunotherapy consisting of fludarabine, cyclophosphamide and rituximab (FCR) over fludarabine and cyclophosphamide (FC) alone, thus establishing FCR regimen as the new gold standard in younger and physically fit patients. However, management of elderly and/or comorbid patients is still a challenging task because they cannot be treated with agressive approaches 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. When deciding about the intensity of treatment, performance status, biological age and number as well as severity of comorbidities should be taken into account. Emerging treatment concepts for elderly/comorbid patients include combination of chlorambucil with monoclonal antibodies (rituximab, ofatumumab, GA-101), fludarabine-based regimens in reduced doses or protocols based on bendamustine and lenalidomide. Combination of high-dose steroids with rituximab represent a promising option in relapsed/refractory CLL; however, infectious toxicity remains a serious issue. Finally, ofatumumab monotherapy appears to be a safe and effective therapy for heavily pretreated patients with CLL. This article reviews the current and future possibilities in the treatment of elderly and comorbid patients with CLL.
Highlights
Chronic lymphocytic leukemia (CLL), the most common leukemic disorder in the Euro-American population [12,35,39] is still considered incurable despite considerable progress in the recent years
Two large randomized studies (German CLL-8 study in untreated patients and international REACH study in relapsed CLL) clearly demonstrated that addition of monoclonal anti-CD20 antibody rituximab to fludarabine and cyclophosphamide (FCR regimen) was associated with significantly higher overal response rate (ORR), complete remissions (CR) and longer progressionfree survival (PFS) [30,47]; patients treated with FCR in first line had significantly longer overall survival – the first clinical study in the history of CLL treatment to achieve this endpoint
Treatment-related mortality was 4 % (3 patients 2x sepsis, 1x pneumonia) [25]. These results suggest that bendamustine might be an effective and above all safe drug for the treatment of elderly CLL patients
Summary
Chronic lymphocytic leukemia (CLL), the most common leukemic disorder in the Euro-American population [12,35,39] is still considered incurable despite considerable progress in the recent years (allogeneic stem cell transplantation being the only potentialy curative treatment for a very small subgroup of highly selected patients). It is a wellknown fact that clinical studies in CLL enroll mainly younger patients in a very good general condition. The median age of patients enrolled in the recent large randomized studies testing fludarabine-based regiments is between 58 and 64 years (7,15,26,30,33,46–48, Table 1). The field of elderly or comorbid patients with CLL has been somewhat neglected in the last 15–20 years as large trials concentrated mainly on younger and fitter patients able to tolerate intensive protocols (reviewed in 18). It is not clear whether older/comorbid patients will profit from newer treat-
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