Abstract / Summary
Richter transformation (RT) is the development of an aggressive lymphoma in a patient with a previous or concomitant diagnosis of chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL). Most cases are of the diffuse large B-cell lymphoma (DLBCL) type; the Hodgkin lymphoma variant and other lymphoma subtypes are less frequent. RT affects 2–10% of patients with CLL, and survival has historically been measured in months. Approximately 80% of DLBCL-RT cases are clonally related to the underlying CLL and are enriched for unmutated IGHV and high-risk genetic lesions such as TP53 disruption, NOTCH1 mutation, CDKN2A/B loss and MYC activation, and they are associated with poorer outcomes than the minority of clonally unrelated cases, which behave as de novo DLBCL. Multi-omic and single-cell studies indicate that the transformed clone is seeded early. Chemoimmunotherapy produces short-lived responses, and treatment has moved towards targeted and immune-based options including BTK inhibitors, CD20 × CD3 bispecific antibodies, checkpoint-inhibitor combinations and CD19 CAR T-cell therapy, with allogeneic transplantation used as consolidation in fit responders. This review summarises the current data on biology, diagnosis, prognosis and treatment of RT and proposes a practical approach.