Comparison of Efficacy of Pembrolizumab between Epstein-Barr Virus‒Positive and ‒Negative Relapsed or Refractory Non-Hodgkin Lymphomas

Abstract

Purpose

Pembrolizumab, a programmed cell death protein 1 (PD1) inhibitor inhibits the interplay between PD1 of T-cell and programmed cell death ligand 1 (PDL1) on tumor cells. Although pembrolizumab has been tried to various subtypes of non-Hodgkin lymphoma (NHL), real-world data about the efficacy of pembrolizumab in NHL patients are limited.

Materials and methods

We analyzed the outcome of 30 relapsed or refractory NHL patients treated with pembrolizumab, and compared the outcome between Epstein-Barr virus (EBV)‒positive and negative subtypes because EBV infection of tumor cells can upregulate PDL1 expression.

Results

Seven patients with EBV-positive NHL showed a response including NK/T-cell lymphoma (6/14, 44%) and primary mediastinal B-cell lymphoma (1/4, 25%) whereas EBV-negative subtypes did not respond such as diffuse large B-cell lymphoma and T-lymphoblastic lymphoma. We also evaluated PDL1 expression using tumor tissue of 76 patients. High PDL1 expression (positive staining of > 50% of tumor cells) was more frequent in NK/T-cell lymphoma and primary mediastinal B-cell lymphoma than other subtypes. Thus, PDL1 expression was significantly higher in EBV-positive (18/32, 56%) than EBV-negative NHL (4/38, 11%, p < 0.001). Furthermore, NK/T-cell lymphoma patients with high PDL1 expression showed a higher response (4/6, 67%) than those with low PDL1 expression (1/5, 20%).

Conclusion

Pembrolizumab could be useful as a salvage treatment for relapsed or refractory EBV-positive NHL, especially NK/T-cell lymphoma. However, its efficacy in EBV-negative NHL with low or absent PDL1 expression is still not clear although pembrolizumab could be a potential treatment option for relapsed or refractory NHL.