Immune checkpoint inhibitors in malignant lymphoma: Advances and perspectives

Classical Hodgkin lymphoma (cHL) has been identified with universal genetic alterations of chromosome 9p24.1, which contains PD-L1/PD-L2 genes. The amplification of 9p24.1 is associated with the increased expression of PD-L1 and PD-L2 on RS cells, which promotes their immune evasion, and subsequently makes cHL sensitive to PD-1 blockade. Several PD-1 inhibitors have shown significant efficacies with overall response rate (ORR) of 70%-90% in relapse/refractory (r/r) cHL and have acquired the approvals for this indication. Recently, more and more studies are conducted to investigate PD-1 blockade in earlier disease course and in combination with neo-agents or chemotherapy. Unlike cHL, non-Hodgkin lymphoma (NHL) consists of numerous subtypes harboring highly biological heterogeneity. Only a few subtypes have been shown to have genetic alteration of9p24.1 including primary mediastinal B cell lymphoma (PMBL), gray zone lymphoma (GZL) with features intermediate between diffuse large B cell lymphoma (DLBCL) and cHL, primary central nervous system lymphoma (PCNSL) and primary testicular lymphoma (PTL). Epstein-Barr virus (EBV)-associated lymphomas have a virally mediated overexpression of PD-L1, also making them sensitive to PD-1 blockade. Therefore, PD-1 inhibitors are less effective in most r/r NHL than in r/r cHL. Further understanding of the biological features of NHL and immune checkpoint inhibitors (ICPi) combined therapy is the research focus in the future. In this review, we outlined the recent progress of ICPi in lymphoma originating from clinical studies.