New Therapies for Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is a clonal lymphoid disease characterized by the proliferation and accumulation of small CD5/CD19/CD23-positive lymphocytes in the blood, lymph nodes, spleen, liver and bone morrow. The management of CLL is determined by the stage and activity of the disease, age and comorbidities. Currently available therapies are only partially efficient, exposing an obvious need to develop better strategies and new, more specific and active drugs. Recently, several new agents have been explored and have shown promise in treating CLL. New mAbs directed against CD20 include veltuzumab (IMMU-106) and obnutuzumab (GA-101), a novel third-generation fully humanized and optimized mAb. Monoclonal antibodies with another target than CD20 can be useful in the treatment of this disease. These treatments include anti-CD37 antibodies (Otlertuzumab and BI 836826) and anti-CD19 mAb (XmAb5574, MEDI-551, hBU12-vcMMAE). Recently, several small molecular kinase inhibitors, including spleen tyrosine kinase inhibitor and Bruton’s tyrosine kinase inhibitors, have been developed to target the proximal B-cell receptor (BCR) signaling pathway. These drugs are part of a promising new strategy for targeted treatment of CLL and are currently undergoing clinical development. The most advanced Bruton’s tyrosine kinase inhibitor in clinical trials is ibrutinib (PCI-32765). Ibrutinib is clinically active in patients with CLL, including high-risk CLL. The oral PI3K p110δ-selective inhibitor idelalisib (CAL-101) also shows preclinical and clinical activity against CLL. Moreover, lenalidomide and bcl-2 inhibitors demonstrate efficacy in CLL in preclinical studies and early clinical trials.