Immune checkpoint inhibitors in malignant lymphoma: Advances and perspectives.

Ningjing Lin,Yuqin Song,Jun Zhu

doi:10.21147/j.issn.1000-9604.2020.03.03

Abstract

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.

Highlights

With the development of immune checkpoint inhibitors (ICPi) and chimeric antigen receptor (CAR)-T cell therapy, immunotherapy began to play an important role in the treatment of cancer
Forty-four patients were treated in the R2 cohort, overall response rate (ORR) was 82% with complete remission (CR) rate of 59% after nivolumab + brentuximab vedotin (BV), and CR increased to 86% after completing BV + bendamustine prior to autologous stem cell transplantation (ASCT)
The AETHERA trial had demonstrated that the median progression-free survival (PFS) was significantly improved in patients in the BV maintenance arm compared to the placebo arm (42.9 vs. 24.1 months, P=0.0013) following ASCT [34]

Summary

Introduction

With the development of immune checkpoint inhibitors (ICPi) and chimeric antigen receptor (CAR)-T cell therapy, immunotherapy began to play an important role in the treatment of cancer. CR was 37% following pembrolizumab monotherapy including three with large mediastinal masses, and CR increased to 100% after 2 cycles of AVD Another prospective, randomized phase II GHSG NIVAHL trial (NCT03004833) [40] enrolled treatment-naïve early-stage unfavorable cHL patients to evaluating nivolumab + AVD followed by 30 Gy involved-site radiotherapy (ISRT). Patients with a shorter time to transplant (≤80 d) appeared to have a higher risk of severe (grade 3−4) aGVHD (6 month CumInc 24% vs 9%, P=0.006) From this extended follow-up of a large international cohort, allo-SCT performed after PD-1 blockade is a feasible strategy associated with a prolonged PFS and a low CIR for this disease. The precise recognition of pseudo-progression can prevent the early discontinuation of ICPi and ensure more benefit from the treatment

Summary

Findings

Conclusions