What is Fitness in the Era of Targeted Agents?

Chronic lymphocytic leukaemia (CLL) is a disease of the elderly, most frequently diagnosed among people aged 65-74 years.¹ Aging brings about a reduction of the functional reserves of organs and systems, translating into a reduced tolerance to treatment. Although aging and frailty are two concepts that have always gone hand-in-hand, chronological age alone is not a sufficient measure of fitness. Some elderly patients have no comorbidity and are functionally independent; others struggle with comorbidities, polypharmacy, functional dependence, or cognition and mood problems. Patients of the same age can have a different ability to tolerate and benefit from treatment. In the past, it was considered as a dogma that the elderly would likely die due to causes unrelated to CLL. A prospective cohort study of 1143 patients across all disease stages demonstrated that although comorbidities were common, the majority of patients died from CLL (46%) or infection (8%) and an additional ∼20% died of other cancers that may be at least indirectly related to CLL.² These results highlight the importance of effective CLL therapy regardless of the presence of concomitant health conditions. Although several studies outlined the independent prognostic role of comorbidities in CLL,^3,4 a German study group, after the analysis of the CLL4 and CLL5 randomized trials, clearly demonstrated that, in patients with comorbidities, it is also critical to deliver treatments that have antileukemic activity and that may be administered without significant loss of dose intensity.⁵.