Therapeutic Approach to Patients with Chronic Lymphocytic Leukemia and Significant Comorbid Conditions.

Clinical trials in chronic lymphocytic leukemia (CLL) have focused mainly on younger fit patients until recently. However, CLL is a disease of elderly and many patients have significant comorbid conditions which together with advanced age preclude the use of aggressive regimens like FCR (fludarabine, cyclophosphamide, rituximab). Therefore, parameters such as performance status, renal function and number/severity of comorbidities together with clinical judgment should be used to guide the decision-making process regarding intensity of treatment. Two large randomized trials recently demonstrated that addition of monoclonal anti-CD20 antibodies (obinutuzumab, rituximab, and ofatumumab) to chlorambucil in untreated comorbid patients lead to improvement in complete remission rate, progression-free survival and even overall survival (obinutuzumab-chlorambucil and rituximab-chlorambucil), with acceptable toxicity profile. Thus, chemoimmunotherapy combining chlorambucil with an anti-CD20 antibody is the new standard approach for elderly/comorbid CLL patients in the first line. Treatment of relapsed/refractory disease in this patient population is very challenging and data regarding this subpopulation are rather limited. Impressive efficacy of novel targeted small molecules interfering with B-cell receptor signaling, namely Bruton tyrosine kinase inhibitor ibrutinib and phosphatidylinositol-3 kinase delta inhibitor idelalisib, radically changed the treatment paradigms for relapsed/refractory CLL; relatively mild toxicity of these agents make them very good candidates for elderly/comorbid patients. Other options for relapsed/refractory disease include alemtuzumab, ofatumumab, high-dose glucocorticoids+rituximab and bendamustine+rituximab. This review summarizes the current knowledge on prognostication and therapy of elderly and comorbid patients with CLL.