PD-1–PD-L1 immune-checkpoint blockade in B-cell lymphomas

Key Points A large percentage of patients with classic Hodgkin lymphoma (CHL), primary mediastinal B-cell lymphoma (PMBCL), primary testicular lymphoma, and primary central nervous system lymphoma have copy-number alterations and/or translocations involving the 9p24.1 locus The 9p24.1 locus contains the genes encoding programmed cell death 1 ligands 1 and 2 (PD-L1 and PD-L2), and JAK2; lymphoma-associated aberrations in this locus result in increased expression of these proteins PD-L1 and/or PD-L2 induce immunosuppressive signalling via programmed cell-death protein 1 (PD-1); blockade of PD-1 with nivolumab results in response rates as high as 87% in patients with relapsed/refractory CHL Nivolumab is currently approved by the FDA for the treatment of relapsed/refractory CHL, and many trials are underway to evaluate PD-1–PD-L1 blockade in patients with B-cell lymphomas The PD-1–PD-L1 axis is probably important for immune evasion of B-cell lymphomas with a viral aetiology, specifically Epstein–Barr virus (EBV)-associated and human immunodeficiency virus (HIV)-associated lymphomas PD-1 inhibition in diffuse large-B-cell lymphoma might be most effective when directed at specific disease subtypes, including PMBCL, T-cell/histiocyte-rich large-B-cell lymphoma, and EBV-positive disease