Richter transformation of chronic lymphocytic leukemia in the era of novel agents

The increased use of several effective novel targeted therapy agents has revolutionized therapy for patients with chronic lymphocytic leukemia (CLL). Disease progression in patients with CLL continues to occur, however. In particular, 3% to 25% of patients treated with a novel agent develop Richter transformation (RT); that is, histologic transformation of CLL to an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). RT that develops in the novel agent era is frequently associated with adverse molecular alterations, such as TP53 disruption and complex karyotype. As a result, patients with RT in the era of novel agents typically have poor responses to the traditional chemotherapy used to treat de novo DLBCL. These patients also tend to have poor survival outcomes, with a median overall survival of less than 1 year. In this article, we review the contemporary literature of RT, particularly in the context of novel agents used for CLL, and discuss the management approach of RT in the novel agent era.