Sequential antigen loss and branching evolution in lymphoma after CD19- and CD20-targeted T-cell-redirecting therapy.

ABSTRACT:

Abstract

CD19 chimeric antigen receptor (CAR) T cells and CD20 targeting T-cell-engaging bispecific antibodies (bispecs) have been approved in B-cell non-Hodgkin lymphoma lately, heralding a new clinical setting in which patients are treated with both approaches, sequentially. The aim of our study was to investigate the selective pressure of CD19- and CD20-directed therapy on the clonal architecture in lymphoma. Using a broad analytical pipeline on 28 longitudinally collected specimen from 7 patients, we identified truncating mutations in the gene encoding CD20 conferring antigen loss in 80% of patients relapsing from CD20 bispecs. Pronounced T-cell exhaustion was identified in cases with progressive disease and retained CD20 expression. We also confirmed CD19 loss after CAR T-cell

SUBMITTER: Duell J 

PROVIDER: S-EPMC10900140 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature