Revisiting Richter transformation in the era of novel CLL agents

Abstract

Richter transformation (RT) is the development of aggressive lymphoma - most frequently diffuse large B-cell lymphoma (DLBCL) and rarely Hodgkin lymphoma (HL) - arising on the background of chronic lymphocytic leukaemia (CLL). Despite recent advances in CLL treatment, RT also develops in patients on novel agents, usually occurring as an early event. RT incidence is lower in CLL patients treated with novel agents in the front line compared to relapsed/refractory cases, with a higher incidence in patients with TP53 disruption. The genetic heterogeneity and complexity are higher in RT-DLBCL than CLL; the genetics of RT-HL are largely unknown. In addition to TP53, aberrations in CDKN2A, MYC, and NOTCH1 are common in RT-DLBCL; however, no distinct RT-specific genetic aberration is recognised yet. RT-DLBCL on ibrutinib is frequently associated with BTK and PLCG2 mutations. Here, we update on genetic analysis, diagnostics and treatment options in RT in the era of novel agents.

Keywords: Chronic lymphocytic leukaemia; Genetics; Ibrutinib; Richter's transformation; TP53 disruption; Venetoclax.