Characterisation of the immune evasion phenotype of Richter Syndrome and the implications for immune checkpoint therapy.

Abstract

Richter syndrome (RS) is the transformation of chronic lymphocytic leukemia (CLL) to a high-grade B-cell lymphoma and is associated with an aggressive clinical course and poor prognosis. Conventional treatment options for RS are generally associated with low response rates and limited durability making this entity an area of significant unmet therapeutic need. Immune checkpoint inhibitor therapy has shown promise in the treatment of some aggressive lymphoma subtypes. In RS, modest benefits have been reported in small phase two trials of anti-PD-1 monotherapy and in combination with ibrutinib, however larger scale studies are lacking (Ding et al Blood, 2017; Jain et al Blood, 2016). We sought to characterise the immune-evasion phenotype of RS focussing on potential genetic biomarkers which may inform the selection of patients who are most likely to benefit from immune-directed therapies.