Treatment of Elderly Patients With Chronic Lymphocytic Leukemia

An Unmet Clinical Need

Stefano Molica; Maura Brugiatelli; Fortunato Morabito; Felicetto Ferrara; Emilio Iannitto; Nicola Di Renzo; Silvana Capalbo; Pellegrino Musto; Francesco Di Raimondo


Expert Rev Hematol. 2013;6(4):441-449. 

In This Article

Abstract and Introduction


In chronic lymphocytic leukemia (CLL), the most prevalent lymphoid malignancy in western countries, patients have a median age at diagnosis of 72 years. In the last few years, there has been remarkable progress in understanding the biology of CLL, the detection of molecular prognostic factors and the development of more effective therapies. However, many of the milestone studies were conducted in populations that were considerably younger than the average age of the CLL population. Today, the challenge is to improve management of elderly patients. In this population, outcome of treatment with newer highly effective therapies is often compromised by comorbidities and poor performance status. Decision on how elderly patients should be treated is thus a complex issue. The management of these patients should rely on the development of risk-stratified treatment strategies based on the assessment of individual functional status and the biologic characteristics of CLL. New single agents with reduced toxic effects (i.e., inhibitors of BCR signalling) that have achieved promising results in Phase I/II studies when available should modify the paradigm of the treatment of elderly patients with CLL.


Chronic lymphocytic leukemia (CLL) is a disease of elderly patients being diagnosed at a median age of 72 years. This translates into an increased incidence of new diagnoses above the age of 65 years up to a rate of 22–30/100,000 per year.[1] Generally, elderly are underrepresented in clinical trials and the choice of therapy in the day-to-day practice for these patients do not rely on solid scientific basis.[2]

An important prognostic factor in the elderly is the burden of comorbidity.[3] Therefore, not only age but several age-related conditions including social environment also determine the choice of treatment of individual patient. Chlorambucil is still the standard of treatment in elderly/unfit CLL patients whereas dose-reduced of purine analog-based combination therapies with or without immunotherapy are currently being investigated within clinical trials.[4] New therapeutic options, mainly based on single agents with reduced toxic effects (i.e., inhibitors of B-cell receptor (BCR) signalling) have achieved promising results in Phase I/II studies, therefore, when available they will eventually offer a valid alternative to chemotherapy.

Here, the authors review background data on fitness criteria, frailty and comorbidities in CLL patients. Based on careful evaluation of published data of larger clinical trials from major referral centers, the authors present the concept of therapy as a guide to an optimal management of older patients with CLL.