PD-1 blockade and lenalidomide combination therapy for chronic active Epstein-Barr virus infection.

Abstract

OBJECTIVES:

Chronic active Epstein-Barr virus infection (CAEBV) is a prototype of EBV-associated T-or NK-cell lymphoproliferative diseases. It is a disease with poor outcome. Almost all current therapies are ineffective except of allogeneic hematopoietic stem cell transplantation.

METHODS:

We investigated the efficacy and safety of programmed death 1 (PD-1) blockade (Sintilimab), combined with lenalidomide, which is an immunomodulatory drug, in an open-label, single-center, prospective study involving CAEBV patients. PD1 blockade 2mg/kg was given every two weeks by intravenous infusion on day 1, and lenalidomide 5mg (age<18 years)/10mg (age ≥ 18 years) was given orally once a day on day 1-14.

RESULTS:

As of Nov 15, 2020, 34 patients were enrolled. As of the Feb 1, 2021 analysis cut-off date, 24 cases completed at least 3 courses and were assessed for efficacy. The overall response rate is 54.2% (13/24, 45.8% complete response; 8.3% partial response). EBV-DNA copies in PBMC decreased significantly (p = 0.002). The proportion of CD8+T cells in lymphocytes increased (p = 0.007). The comparative analysis between response group and non-response group showed the proportion of Effector Memory CD8+ T cells and cytokines of CTLs activation (IFN-γ, CD27, CD30, MIG, IP-10) increased significantly in Response-group after treatment. Whole-exome sequencing generated from peripheral blood and saliva samples reveal that Non-Response group had a higher somatic mutational load of copy number variation in background. With a median follow-up time of 17.8 months, 22 of 24 patients were alive with an estimated survival probability of 91.3% at 1 year. All 34 patients were assessed for safety evaluation. The possible drug-related adverse events were reported in 17 (50%) patients.

CONCLUSIONS:

PD-1 blockade combined with lenalidomide was an effective and safe therapy for CAEBV patients. The significant therapeutic effect and the different characteristics between response and non-response group, provides a possible predictive value for CAEBV treatment option.

• Authors: Yue Song, Jingshi Wang, Yini Wang, Lin Wu, Yahong You, Deli Song, Leilei Chen, Gaungqiang Meng, Xiaodan He, Tingting Cui, Xiaodi Wang, Qingxia Yin, Zhao Wang
• Journal: Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases (Clin Microbiol Infect) Vol. 29 Issue 6 Pg. 796.e7-796.e13 (Jun 2023) ISSN: 1469-0691 [Electronic] England
• PMID: 36702399 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Lenalidomide
• Programmed Cell Death 1 Receptor

Topics

• Humans
• Adolescent
• Epstein-Barr Virus Infections (complications)
• Herpesvirus 4, Human (genetics)
• Lenalidomide (therapeutic use)
• Programmed Cell Death 1 Receptor
• Leukocytes, Mononuclear
• DNA Copy Number Variations
• Prospective Studies
• Chronic Disease