Chronic lymphocytic leukaemia (CLL) mainly affects elderly patients.1 With the increasing comorbidity burden and frailty in elderly patients, evaluation of functional status before treatment initiation is essential. So far, there is no ideal tool to measure the comorbidity burden, but geriatric assessment for example, with the G8 score2 before treatment initiation, is strongly recommended.3,4 While more intensive combination regimens based on chemotherapy plus antibody, such as the combination of fludarabine, cyclophosphamide, and rituximab (FCR), are standard in younger and/or physically fit patients, with concomitant diseases and physical fitness playing a major role in the selection of treatment for the elderly who do not tolerate such regimens well.5 Dose reductions or milder chemoimmunotherapy regimens are well tolerated in the elderly and yield promising results.6,7 The combination of chlorambucil plus a CD20 antibody has become the new standard first-line therapy in many countries because it yields long progression-free survival (PFS) rates of 15–27 months.8-10 Data from the CLL11 study presented at European Hematology Association (EHA) Congress 2016 showed that achieving a negative measure of minimal residual disease in peripheral blood or bone marrow by polymerase chain reaction was associated with significantly longer PFS among elder patients being treated with chlorambucil plus rituximab or obinutuzumab.11
With the approval of new oral drugs that inhibit kinases attached to the B cell receptor, better treatment options which are well tolerated are now available for relapsed CLL patients12,13 as well as front-line therapy.14 A randomised Phase III study in elderly CLL patients showed a clear superiority of the Bruton’s tyrosine kinase inhibitor ibrutinib over chlorambucil alone for PFS and overall survival.14 However, even in a front-line setting minimal residual disease negativity is rarely achieved with the new substances. With these continuously administered substances, drug interactions and compliance have to be considered, particularly in elderly patients. A retrospective analysis presented at EHA 2016 showed that a different side effect profile has to be considered with each new compound, as for example atrial fibrillation, which may occur in elderly patients receiving ibrutinib.15 Current studies are investigating the bcl2 inhibitor venetoclax in front-line therapy of elderly. The combination with obinutuzumab was shown to be safe in a run-in phase study.16 These as well as many other data presented at EHA 2016 regarding kinase inhibitors show that the selection of optimal treatment for elderly CLL patients remains challenging.
