Modern Approach to Prognostication and Therapy of Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is the most common adult lymphoid malignancy in the Euro-American population and affects predominantly older individuals: median age at the time of diagnosis lies between 65 and 72 years. Because of the remarkably heterogeneous prognosis of CLL and the fact that most patients are currently diagnosed in early, asymptomatic clinical stages not requiring therapy, prognostic factors such as cytogenetic aberrations, mutation of the TP53 gene, and mutational status of the immunoglobulin heavy chain variable region (IGHV) are extremely useful for refinement of individual patient’s prognosis. These markers can also help with the selection of therapeutic approach. The treatment paradigm in CLL has recently shifted from chemoimmunotherapy to novel, orally available targeted agents, namely, Bruton tyrosine kinase inhibitors ibrutinib and acalabrutinib and bcl-2 inhibitor venetoclax (in monotherapy or in combination with anti-CD20 monoclonal antibodies rituximab or obinutuzumab). These agents are considered standard options in relapsed/refractory CLL as well as previously untreated population. Chemoimmunotherapy (especially fludarabine-cyclophosphamide-rituximab [FCR] in younger fit patients, bendamustine-rituximab [BR] or obinutuzumab-chlorambucil [G-CLB] in elderly/comorbid patients) can still be considered in patients with biologically favorable prognosis (e.g., mutated IGHV status and 13q deletion) or rarely as the second-line treatment in case of a long-lasting remission after first-line therapy.