Abstract
Chronic lymphocytic leukemia (CLL) is one of the most common types of leukemia among elderly patients. The disease can behave quite heterogeneously, as certain CLL patients will experience an indolent course, whereas others endure an aggressive course with poor outcomes. Several prognostic indicators exist to stratify CLL patients into risk groups aimed at predicting disease course and outcomes to treatment modalities. Patients with high-risk disease features such as deletion 17p (del[17p]) and/or tumor suppressor gene (TP53) mutations or early relapse following fludarabine-based therapy once had limited therapeutic options, with only allogeneic stem cell transplantation (alloSCT) considered a curative option. The advent of novel oral targeted agents inhibiting key proteins in signaling pathways important for CLL survival and proliferation has shown improved outcomes, in particular for high-risk patients and in the relapsed or refractory setting. Optimal selection and sequencing of these treatments can pose challenges as new data emerge on disease-based factors with patient outcomes. Although several ongoing clinical trials are investigating the use of combination therapy with new oral targeted agents, this article will review only currently approved treatment options for first-line and relapsed or refractory CLL patients based on risk stratification with an emphasis on the sequencing of therapies
