Chronic Lymphocytic Leukemia

Advances in the understanding of the molecular pathogenesis of chronic lymphocytic leukemia (CLL) have led to the discovery of novel targeted therapies. Over the last decade, targeted therapy with monoclonal antibodies (mAb) in combination with chemotherapy has been used routinely in CLL. The most commonly used mAbs are those targeting the CD20 epitope-rituximab, ofatumumab, and obinutuzumab. In recent years, targeted therapy involved agents inhibiting kinases in the B-cell receptor (BCR) signaling pathway. BCR signaling is crucial for the survival, proliferation, growth, differentiation, and migration of CLL cells. Important kinases involved in BCR signaling include BTK, p110PI3Kδ, and SYK. We will discuss the clinical efficacy of agents, which block BCR signaling such as ibrutinib (BTK inhibitor), idelalisib (p110PI3Kδ inhibitor), and other novel BCR signaling inhibitors; combination therapy with mAbs, drug resistance, and future perspectives; and other targeted therapeutics such as Bcl2 antagonists (e.g., ABT-199) and cyclin inhibitors (e.g., alvocidib).