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High-grade transformation of chronic lymphocytic leukaemia [Richter syndrome (RS)] is rare and represents a unique and uncommon clinical challenge. Clonally related diffuse large B cell type RS is a chemotherapy-resistant and devastating disease. Patients are typically elderly, immunosuppressed and present with a rapidly deteriorating performance status. Historical outcomes suggest a median overall survival of approximately 8 months. RS remains is an area of high unmet clinical need. The molecular profile and treatment needs of patients are likely to change over time with the advent of novel B cell receptor inhibitors, monoclonal antibodies and BH3 mimetics. Herein, we summarise what is known regarding the molecular drivers of RS and the existing clinical trial data, including the recently published CHOP-OR (cyclophosphamide, doxorubicin, vincristine, prednisolone and ofatumumab followed by ofatumumab maintenance in newly diagnosed RS) trial. We discuss novel agents in development with a focus on the second-generation Bruton tyrosine kinase inhibitor acalabrutinib, checkpoint inhibition and the potential role of precision medicine in future trials of RS.

Original publication

DOI

10.1111/bjh.14700

Type

Journal article

Journal

Br J Haematol

Publication Date

08/2017

Volume

178

Pages

508 - 520

Keywords

Bruton's tyrosine kinase, Richter syndrome, TP53, acalabrutinib, chronic lymphocytic leukaemia, ofatumumab, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Cell Transformation, Neoplastic, Cyclophosphamide, Disease Progression, Doxorubicin, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse, Positron Emission Tomography Computed Tomography, Prednisone, Syndrome, Vincristine