Efficacy and safety of orelabrutinib plus R-CDOP as first-line therapy in diffuse large B-cell lymphoma with high-risk CNS-IPI: a prospective, multicenter, single-arm, phase II study
7 affiliations
- 1Department of Hematology, Zhejiang University
- 2Department of Hematology, Changde Hospital, Xiangya School of Medicine, Central South University (First People’s Hospital of Changde City)
- 3Department of Hematology, The Affiliated Hospital of ShaoXing University (ShaoXing Municipal Hospital), Shaoxing, Zhejiang People’s Republic of China
- 4Department of Hematology, The Second Affiated Hospital Zhejiang University School of Medicine
- 5Department of Hematology, Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University
- 6Department of Hematology, Taizhou Hospital of Zhejiang Province
- 7Department of Hematology, The Second Affiliated Hospital of Jiaxing University
Abstract
Background: Diffuse large B-cell lymphoma (DLBCL) patients central nervous system international prognostic index (CNS-IPI) ≥4 have a high risk of central nervous system (CNS) relapse and poor prognosis. Orelabrutinib, a next-generation Bruton’s tyrosine kinase (BTK) inhibitor with excellent blood-brain barrier (BBB) penetration. This study evaluated orelabrutinib plus R-CDOP as first-line therapy in this high-risk population.
Methods: This prospective, multicenter, single-arm, phase II trial (ClinicalTrials.gov: NCT06290817) enrolled untreated DLBCL patients with CNS-IPI ≥4. Patients received six 21-day cycles of orelabrutinib (150 mg orally once daily) plus R-CDOP. The primary endpoint was objective response rate (ORR) at the end of the induction; secondary endpoints included complete response (CR) rate, progression-free survival (PFS), overall survival (OS), cumulative incidence of CNS relapse, and safety.
Results: Between March 2021 and September 2024, 44 patients were enrolled and constituted the intention-to-treat (ITT) population. Median age was 63 years, 64.9% had double-expressor lymphoma. In the ITT population, the ORR at the end of induction was 70.5% (31/44, 95% confidence interval [CI]: 55.3–82.1), with a CR rate of 50.0% (22/44, 95% CI: 35.1–64.9). In the per-protocol population of 37 evaluable patients, the ORR and CR rate at the end of induction were 75.7% (28/37, 95% CI: 59.9–86.9) and 59.5% (22/37, 95% CI: 43.4–73.9), respectively. At a median follow-up of 22.6 months, median PFS was not reached. The 1- and 2-year PFS rates were 77.6% (95% CI: 64.5–90.7) and 57.4% (95% CI: 40.9–73.9). Median OS was 38.1 months, with 1- and 2-year OS rates of 93.8% (95% CI: 86.2–100) and 90.2% (95% CI: 80.4–100). The 1- and 2-year cumulative incidences of CNS relapse were 0% and 9.3%, respectively. All patients had treatment-related adverse events (TRAEs); grade 3–4 TRAEs occurring in 67.6%, mainly neutropenia (59.5%), anemia (24.3%), and thrombocytopenia (16.2%). No unexpected toxicities or treatment-related deaths were observed.
Conclusion: In previously untreated DLBCL patients with high-risk CNS-IPI, orelabrutinib plus R-CDOP demonstrated promising antitumor activity and a low observed rate of CNS relapse. Hematologic toxicity was frequent, but was clinically manageable with standard supportive care. These findings should be considered hypothesis-generating and warrant validation in randomized controlled trials.
Clinical trial registration: ClinicalTrials.gov, identifier NCT06290817.
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BibTeX
@article{guo2026efficacy,
title = {{Efficacy and safety of orelabrutinib plus R-CDOP as first-line therapy in diffuse large B-cell lymphoma with high-risk CNS-IPI: a prospective, multicenter, single-arm, phase II study}},
author = {Yiding Guo and Jun Wang and Huyi Lei and Changqian Bao and Panpan Chen and Lihong Shou and Qunyi Guo and Beili Hu and Yongsheng Xie and Shuhan Zhong and Wenbin Qian and Xibin Xiao},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1976858},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1976858/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Efficacy and safety of orelabrutinib plus R-CDOP as first-line therapy in diffuse large B-cell lymphoma with high-risk CNS-IPI: a prospective, multicenter, single-arm, phase II study
AU - Yiding Guo
AU - Jun Wang
AU - Huyi Lei
AU - Changqian Bao
AU - Panpan Chen
AU - Lihong Shou
AU - Qunyi Guo
AU - Beili Hu
AU - Yongsheng Xie
AU - Shuhan Zhong
AU - Wenbin Qian
AU - Xibin Xiao
PY - 2026
DA - 2026/10/21
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1976858
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1976858/full
AB - Background: Diffuse large B-cell lymphoma (DLBCL) patients central nervous system international prognostic index (CNS-IPI) ≥4 have a high risk of central nervous system (CNS) relapse and poor prognosis. Orelabrutinib, a next-generation Bruton’s tyrosine kinase (BTK) inhibitor with excellent blood-brain barrier (BBB) penetration. This study evaluated orelabrutinib plus R-CDOP as first-line therapy in this high-risk population. Methods: This prospective, multicenter, single-arm, phase II trial (ClinicalTrials.gov: NCT06290817) enrolled untreated DLBCL patients with CNS-IPI ≥4. Patients received six 21-day cycles of orelabrutinib (150 mg orally once daily) plus R-CDOP. The primary endpoint was objective response rate (ORR) at the end of the induction; secondary endpoints included complete response (CR) rate, progression-free survival (PFS), overall survival (OS), cumulative incidence of CNS relapse, and safety. Results: Between March 2021 and September 2024, 44 patients were enrolled and constituted the intention-to-treat (ITT) population. Median age was 63 years, 64.9% had double-expressor lymphoma. In the ITT population, the ORR at the end of induction was 70.5% (31/44, 95% confidence interval [CI]: 55.3–82.1), with a CR rate of 50.0% (22/44, 95% CI: 35.1–64.9). In the per-protocol population of 37 evaluable patients, the ORR and CR rate at the end of induction were 75.7% (28/37, 95% CI: 59.9–86.9) and 59.5% (22/37, 95% CI: 43.4–73.9), respectively. At a median follow-up of 22.6 months, median PFS was not reached. The 1- and 2-year PFS rates were 77.6% (95% CI: 64.5–90.7) and 57.4% (95% CI: 40.9–73.9). Median OS was 38.1 months, with 1- and 2-year OS rates of 93.8% (95% CI: 86.2–100) and 90.2% (95% CI: 80.4–100). The 1- and 2-year cumulative incidences of CNS relapse were 0% and 9.3%, respectively. All patients had treatment-related adverse events (TRAEs); grade 3–4 TRAEs occurring in 67.6%, mainly neutropenia (59.5%), anemia (24.3%), and thrombocytopenia (16.2%). No unexpected toxicities or treatment-related deaths were observed. Conclusion: In previously untreated DLBCL patients with high-risk CNS-IPI, orelabrutinib plus R-CDOP demonstrated promising antitumor activity and a low observed rate of CNS relapse. Hematologic toxicity was frequent, but was clinically manageable with standard supportive care. These findings should be considered hypothesis-generating and warrant validation in randomized controlled trials. Clinical trial registration: ClinicalTrials.gov, identifier NCT06290817.
SN - 2234-943X
ER -