IGH::CD274 (PD‐L1) rearrangement in diffuse large B cell lymphoma and its therapeutic implication

Abstract Diffuse large B cell lymphoma (DLBCL) expresses abundant programmed death ligand 1 (PD‐L1), which shields tumor cells from immune attacks through the PD‐L1/PD‐1 signaling axis. The mechanism of PD‐L1 overexpression includes the deletion of the 3′end of PD‐L1, which increases its mRNA stability, and the gain or amplification of PD‐L1. Previous studies found two cases of DLBCL carrying an IGH::PD‐L1 by whole genome sequencing. We describe two more such cases by a targeted DNA next‐generation sequencing (NGS) capable of detecting IGH rearrangements, leading to PD‐L1 overexpression. DLBCL with PD‐L1 overexpression is often resistant to R‐CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine and prednisolone). Our patients responded to a combination of R‐CHOP and a PD‐1 inhibitor