Treatment of Richter Transformation of Chronic Lymphocytic Leukemia in the Modern Era

SIMPLE SUMMARY: Though rare, Richter Transformation (RT) is a serious complication of chronic lymphocytic leukemia. RT carries a high mortality rate and represents an unmet clinical need. With an improved understanding of its molecular biology, there is hope that novel targeted therapies and immunotherapies will lead to improved outcomes in this disease. This review outlines what is known about RT as well as where the field is headed. An illustrative case is also included to facilitate the reader’s understanding of the material presented. ABSTRACT: Richter Transformation (RT) refers to the development of an aggressive lymphoma in the setting of chronic lymphocytic leukemia (CLL). While many variants of RT are recognized, diffuse large B-cell lymphoma (RT-DLBCL) is the most common (80%), followed by Hodgkin’s lymphoma (RT-HL, 19%). Diagnosis is based upon histologic evaluation of clinically suspicious lymph nodes. Positron emission tomography (PET) may be used to select the node of interest for biopsy. Although clonality testing is not a prerequisite of RT diagnosis, it has significant implications for survival. Clonally related DLBCL carries the worst prognosis with a median overall survival (OS) of less than one year in the era of combination chemotherapies with or without anti-CD20 antibodies. Prognosis has improved with the use of stem cell transplant and newer agents such as targeted therapy and newer forms of immunotherapy. Consideration of a clinical trial is encouraged. This review describes our current understanding of RT and focuses on treatment of RT-DLBCL, including clinical trials in progress and new therapies in development. We also report an illustrative example of a patient with clonally related DLBCL who survived two years after diagnosis without the use of combination chemotherapy.