ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1629224
This article is part of the Research TopicPrecision Immunotherapy and Novel Target Discovery in Hematological MalignancyView all 15 articles
Safety and clinical outcomes of orelabrutinib, lenalidomide plus sintilimab for relapsed/refractory diffuse large B-cell lymphoma
Provisionally accepted
Lingling Wang1
Yongfen Huang1Dan Xu2Xiaoyong Wang3Hailiang Chu4
Chunling Wang5
Hao Xu1
Wei Sang6
Yuexin Cheng1
Yuqing Miao1*- 1The First People's Hospital of Yancheng, Yancheng, China
- 2Funing People's Hospital, Yancheng, China
- 3Dongtai People's Hospital, Yancheng, China
- 4Bozhou Hospital Affiliated to Anhui Medical University, Bozhou, China
- 5The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, China
- 6Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
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This study evaluated the safety and clinical outcomes of orelabrutinib, lenalidomide plus sintilimab in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Thirty-four patients were given orelabrutinib 150 mg once daily, lenalidomide 25 mg once daily on days 1–10, and sintilimab 200 mg intravenously on day 1 of each 21-day cycle. With a median follow-up of 9 months (95% CI, 8.3-9.6), 7 patients died. The 1-year progression-free survival (PFS) and overall survival (OS) were 41.9% and 77.8%, respectively. The median PFS was 6 months (95% CI, 3.4-8.6), and median OS was not reached. The median exposure time was 4 months, while the median time to first response was 2 months. The best objective response rate (ORR) was 58.8%, with a complete remission (CR) rate of 38.2%. Twenty-eight (82%) patients presented with treatment-related adverse events (TRAEs), and 7 (20.6%) patients developed grade 3 or higher TRAEs. The most common grade 1 TRAEs were neutropenia (64.7%), thrombopenia (44.1%), skin rash (32.4%), and fatigue (29.4%). Patients who responded to treatment had a higher proportion of PD1+CD8+ T cells, a lower percentage of CD8+ T cells, and a higher percentage of CD4+ T cells and lower C-reactive protein (CRP) levels at baseline. Cytokines such as IL-6, IL-8, and IL-10 levels were also substantially lowered in these patients. Orelabrutinib, lenalidomide plus sintilimab demonstrated promising efficacy and a manageable safety profile in Chinese patients with R/R DLBCL.
Keywords: Diffuse large B-cell lymphoma, Relapsed/refractory, Immunotherapy, Bruton tyrosine kinase inhibitors, Anti-programmed cell death-1 monoclonal antibody
Received: 15 May 2025; Accepted: 14 Aug 2025.
Copyright: © 2025 Wang, Huang, Xu, Wang, Chu, Wang, Xu, Sang, Cheng and Miao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yuqing Miao, The First People's Hospital of Yancheng, Yancheng, China
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