Novel and emerging drugs for chronic lymphocytic leukemia

During the last decades advanced treatment options for chronic lymphocytic leukemia have enabled the shift from rather ineffective palliative treatment to therapies that are aiming for long lasting complete remission and prolongation of survival. This remarkable progress was achieved by combining conventional chemotherapy with monoclonal antibodies such as rituximab and alemtuzumab. Despite this improvement, CLL remains an incurable disease and all patients will eventually relapse and become refractory to treatment. Allogeneic stem cell transplantation is the only curative option but is feasible only in a minority of patients due to the comorbidity and impaired physical fitness of many patients, since the mean age at first diagnosis lies between 70 and 75 years. Therefore, novel less-toxic therapeutic agents are needed, particularly for patients with comorbidities or high-risk cytogenetic abnormalities. Research in the field of CLL and growing understanding of the pathogenesis of B-cell lymphomas has produced a wide variety of new substances for different targets, e.g. different novel monoclonal antibodies, immunomodulatory agents and inhibitors targeting different kinases of B-cell receptor signalling cascade, such as Bruton tyrosine kinase (BTK) and phosphatidylinositol-3-kinase (PI3K). This article reviews novel drugs that were recently developed for the use in CLL. The agents discussed in this article were selected for having already shown preliminary evidence of clinical activity.