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

Over the last decades, a revolution has occurred in oncology with the development of immune checkpoint inhibitors (ICIs). Following tremendous successes in solid tumors, interest has risen to explore these inhibitors in hematologic malignancies; while Hodgkin's lymphoma (HL) has shown overwhelming achievements, available data on different types of non-Hodgkin's lymphoma (NHL) vary considerably. To the best of our knowledge, no meta-analysis has assessed the efficacy and safety of ICI therapy in relapsed or refractory NHL patients. Meta-analysis of the included studies (n = 29) indicated PD-1 may probably be the more attractive ICI target rather than PD-L1 and CTLA-4 in NHL patients. Also, there is a plausible correlation between NHL subtypes and response to ICI therapy. While MF, ENKTL, RT, and PMBCL showed promising responses to ICI monotherapy, neither FL nor DLBCL had satisfactory responses; further necessitating novel strategies such as the application of ICIs in combination with other treatment strategies. Notably, among different combinations, BTK inhibitors showed an obvious improvement as compared to ICI monotherapy in both FL and DLBCL, however, the best results were obtained when ICI was combined with anti-CD20 monoclonal antibodies. Finally, while most NHL patients who received ICI treatment have experienced mild AEs, larger trials with long-term follow-up are required to confirm the safety, as well as the efficacy, of ICI therapy in NHL patients.

Automated summary

In recent decades, the development of immune checkpoint inhibitors (ICIs) in oncology has brought about a revolution. While tremendous successes have been seen in solid tumors, the application of ICIs in hematologic malignancies, especially non-Hodgkin's lymphoma (NHL), varies considerably. Meta-analysis of the included studies suggests that PD-1 may be a more attractive target in NHL patients compared to PD-L1 and CTLA-4. Additionally, the response to ICI therapy may be correlated with NHL subtypes, with different subtypes showing varying levels of response. Combination strategies, such as the use of ICIs with other treatment approaches, may be necessary to improve efficacy in NHL patients, especially for FL and DLBCL. Furthermore, larger trials with long-term follow-up are needed to confirm the safety and efficacy of ICI therapy in NHL patients.