Optimal Pharmacotherapeutic Management of Chronic Lymphocytic Leukaemia

Although the majority of patients with chronic lymphocytic leukaemia (CLL) are of advanced age, these patients have not been well represented in past clinical trials. This has resulted in a lack of evidence that has complicated treatment in this patient group. However, data from an increasing number of subgroup analyses of recent trials as well as from trials specifically designed for elderly patients with CLL have provided some insight into the feasibility of the available treatments, thus allowing development of the first evidence-based recommendations for the pharmacotherapeutic management of these patients. Physically fit patients without significant co-morbidity are likely to benefit from the standard treatment of fludarabine, cyclophosphamide and rituximab (FCR). However, whether treatment with purine analogues and/or CD20 antibodies is also beneficial in physically unfit patients suffering from additional health problems remains to be determined. Latest data suggest that the alkylating drug chlorambucil rather than fludarabine is a reasonable chemotherapeutic backbone for chemoimmunotherapy in these patients. Trials are now underway to investigate combinations of chlorambucil with rituximab or with novel CD20 antibodies (GA101 [afutuzumab], ofatumumab) in older CLL patients. In parallel, other regimens, including bendamustine or lenalidomide with or without the addition of rituximab, low-dose fludarabine and low-dose FCR, hold promise in elderly patients with previously untreated or relapsed CLL.