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

来那度胺 医学 免疫学 CD8型 内科学 造血干细胞移植 淋巴增殖反应 病毒载量 移植 外周血单个核细胞 胃肠病学 病毒 肿瘤科 免疫系统 生物 多发性骨髓瘤 体外 生物化学
作者
Yue Song,Jingshi Wang,Yini Wang,Wei Lin,Yahong You,Dongmei Song,Leilei Chen,Gaungqiang Meng,Xiaodan He,Tingting Cui,Xiaodi Wang,Qingxia Yin,Zhao Wang
出处
期刊:Clinical Microbiology and Infection [Elsevier]
卷期号:29 (6): 796.e7-796.e13 被引量:4
标识
DOI:10.1016/j.cmi.2023.01.017
摘要

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.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.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.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.
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