A systematic review and meta-analysis ofimmune checkpoint therapy in relapsed or refractory non-Hodgkin lymphoma; a friend or foe?

Introduction: Over the last decades, a revolution has occurredin oncology with the development of immune checkpoint inhibitors(ICIs). Following tremendous successes in solid tumors,interest has risen to explore these inhibitors in hematologicmalignancies; while Hodgkin's lymphoma (HL) has shownoverwhelming achievements, available data on different typesof non-Hodgkin's lymphoma (NHL) vary considerably. To thebest of our knowledge, this is the first study that assesses the efficacyand safety of ICI therapy in relapsed or refractory NHLcases.Materials and Methods: The search was conducted on Pub-Med, Web of Science, and Scopus from their inception to February۵, ۲۰۲۲. Our primary objective was to investigate the rateof ORR, DCR, and PD following administration of ICIs in patientswith relapsed or refractory NHL. The secondary outcomewas the pooled risk of adverse events. Furthermore, we conductedsubgroup analysis according to the monotherapy of ICIsor in combination with conventional therapies, type of NHL,and type of ICI.Results: Meta-analysis of the included studies (n=۲۹) indicatedPD-۱ may probably be the more attractive ICI target rather thanPD-L۱ and CTLA-۴ in NHL cases. Also, there is a plausiblecorrelation between NHL subtypes and response to ICI therapy.While MF, ENKTL, RT, and PMBCL showed promisingresponses to ICI monotherapy, neither FL nor DLBCL had satisfactoryresponses; further necessitating novel strategies suchas the application of ICIs in combination with other lines oftherapies. Notably, among different combinations, BTK inhibitorsshowed an obvious improvement as compared to ICI monotherapyin both FL and DLBCL, however, the best results wereobtained when ICI was combined with anti-CD۲۰. Finally, ourmeta-analysis confirmed that most NHL cases who received ICItreatment have experienced mild AEs.Conclusion: ICI therapy indicated encouraging efficacy andfavorable safety profile in NHL patients, thus, could be an alternativetreatment option