Richter's transformation: Transforming the clinical landscape

Richter transformation (RT) represents an aggressive histological transformation from chronic lymphocytic leukaemia, most often to a large B cell lymphoma. It is characterised by chemo-resistance and subsequent short survival. Drug development has struggled over recent years in light of the aggressive kinetics of the disease, lack of pivotal registrational trials and relative rarity of the phenomenon. In this review we will highlight the diagnostic and therapeutic challenges of managing patients with RT as well as taking a look to the future therapeutic landscape. Highly active therapies developed across B cell malignancies are starting to impact this field, with T-cell activation therapies (CAR-T, bispecific antibodies), antibody-drug conjugates, and novel small molecule inhibitor combinations (e.g. BTKi-BCL2i) being actively studied. We will highlight the data supporting these developments and look to the studies to come to provide hope for patients suffering from this devastating disease.