Orelabrutinib-bruton tyrosine kinase inhibitor-based regimens in the treatment of central nervous system lymphoma: a retrospective study

Wu, Jingjing; Wang, Wenhua; Meng, Di; Ma, Shanshan; Zhang, Xudong; Zhu, Linan; Niu, Songtao; Ding, Mengjie; Zhang, Jieming; Zhang, Lei; Li, Xin; Li, Ling; Sun, Zhenchang; Wang, Xinhua; Fu, Xiaorui; Li, Zhaoming; Chang, Yu; Nan, Feifei; Yan, Jiaqin; Yu, Hui; Wu, Xiaolong; Zhou, Zhiyuan; Zhang, Mingzhi

doi:10.1007/s10637-022-01219-5

Cited by 24 publications

(33 citation statements)

References 28 publications

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“…[34][35][36] A retrospective study of 23 patients with CNSL found that the 6-month PFS rates of patients with newly diagnosed CNSL and patients with relapsed/refractory CNSL were 100% and 67.70%, respectively, with the treatment regimen based on osimertinib. 37 This is inconsistent with our research results, and the reason for this may be the small sample size and the short follow-up period. In particular, as a new drug just approved on the market on December 25, 2020, there are few clinical data for reference.…”

contrasting

confidence: 95%

Expression and Clinical Significance of Th1/Th2/Th17 Cytokines and Lymphocyte Subsets in PCNSL

Bian¹,

Wang²,

Gao³

et al. 2022

JIR

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Primary central nervous system lymphoma (PCNSL) responds favorably to radiation, chemotherapy and targeted drug therapy. However survival is usually worse, the treatment-related drug resistance and recurrence are still clinical problems to be solved urgently. Studies have shown that cytokines are expressed in varying degrees in patients with lymphoma, which is significantly related to the progression, poor prognosis and drug resistance of lymphoma. We explore the expression and clinical significance of Th1/Th2/ Th17 cytokines and lymphocyte subsets in patients with PCNSL to provide a more sufficient theoretical basis for its diagnosis and treatment. Patients and Methods: We measured and analysed the levels of Th1/Th2/Th17 cytokines and the distribution of lymphocyte subsets (including Treg cells, CD3+, CD4+, CD8+, CD19+, and CD4+/CD8+) in 39 patients with PCNSL and 96 patients with diffuse large B-cell lymphoma (DLBCL) without central nervous system involvement. The cytokines of 13 healthy people and the lymphocyte subsets of 27 healthy people were measured as the control group. Results: We found a significant difference in the level of Th1/Th2/Th17 cytokines and lymphocyte subsets between PCNSL and healthy controls, especially IL-2, after treatment, which was significantly higher than before treatment (p<0.01). However, the level of CD19+ and CD4+/CD8+ decreased while CD8+ and CD3+ increased after treatment (regardless of whether the treatment was effective), and the difference was statistically significant. In addition, our analysis of different prognostic factors found that HD-MTX-based chemotherapy appears to have a longer progression-free survival and overall survival than osimertinib-based chemotherapy. Conclusion:There are significant differences in Th1/Th2/Th17 cytokines and lymphocyte subsets among PCNSL, DLBCL, and healthy controls, and their detection is helpful for the diagnosis, treatment, and prognosis of PCNSL. HD-MTX-based chemotherapy may still be the first choice for PCNSL.

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contrasting

confidence: 95%

Expression and Clinical Significance of Th1/Th2/Th17 Cytokines and Lymphocyte Subsets in PCNSL

Bian¹,

Wang²,

Gao³

et al. 2022

JIR

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“…In addition, short-course RMT therapy may reduce toxicity in our study. As known, atrial fibrillation, bleeding and infectious complications are common AEs related to BKT inhibitors ( 37 ); however, these were not reported in our study, which may be attributed to the high target selectivity and low off-target reactivity of orelabrutinib ( 18 ). Besides, no unexpected AEs and grade 4 or more AEs and cardiotoxicity were observed in the present study.…”

Section: Discussionmentioning

confidence: 54%

“…It has been approved by National Medical Products Administration for the treatment of mantle cell lymphoma and chronic lymphocytic leukemia. Results of several studies have demonstrated the anti-tumor activity and manageable safety profile of orelabrutinib ( 18 , 19 ). Besides, tirabrutinib as a BTK inhibitor was approved for the treatment of PCNSL ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

Orelabrutinib Combined With Lenalidomide and Immunochemotherapy for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Retrospective Analysis of Case Series

et al. 2022

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BackgroundRelapsed/refractory (r/r) primary central nervous system lymphoma (PCNSL) is an intractable situation without sound treatment. Bruton’s tyrosine kinase (BTK) represents an attractive drug target in PCNSL. Orelabrutinib is a new-generation BTK inhibitor with high cerebrospinal fluid (CSF) concentration. This study aimed to evaluate the efficacy and safety of orelabrutinib-containing combination therapy in patients with r/r PCNSL.MethodsWe retrospectively analyzed r/r PCNSL patients who received combination therapy with rituximab, high-dose methotrexate, temozolomide, orelabrutinib and lenalidomide, and further explored the relationship between the efficacy and genetic characteristics.ResultsA total of fifteen patients were included in this retrospective study. The overall response rate (ORR) was 86.7%, the complete remission (CR) rate was 73.3% and the disease control rate (DCR) was 93.3%. Among 13 responders, 9 patients are still receiving oral orelabrutinib and lenalidomide. The most common adverse event (AEs) was transaminase increase (66.7%). No grade 4 AE or drug-related death was reported. Genomic sequencing showed that patients who responded to orelabrutinib had abnormal NF-κB activation, while those who had no response were mainly enriched with transcriptional misregulation. Patients who had mutations in TLR, BCR, or NF-κB pathway achieved complete or partial response to the orelabrutinib-containing therapy. Moreover, the blood and cerebrospinal fluid circulating tumor DNA (ctDNA) were closely associated with tumor recurrence and treatment response and sustained tumor responses correlated with the clearance of ctDNA.ConclusionOrelabrutinib-containing regimen was effective and well-tolerated in patients with r/r PCNSL. Genome sequencing of tumor samples could help to screen patients who may respond to the orelabrutinib-containing regimen, and liquid biopsy may contribute to tracing tumor burden and monitoring treatment response.

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“…As for two other BTKi currently available in China, 23 and 16 CNSL patients treated with orelabrutinib or zanubrutinib, respectively, were reported in a retrospective study, or in case series. The outcomes of these BTKi for PCNSL need to be followed-up [86][87][88].…”

Section: Bruton's Tyrosine Kinase Inhibitor (Btki)mentioning

confidence: 99%

Evidence-based expert consensus on the management of primary central nervous system lymphoma in China

et al. 2022

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Primary central nervous system lymphoma (PCNSL) is a type of central nervous system restricted non-Hodgkin lymphoma, whose histopathological diagnosis is majorly large B cell lymphoma. To provide specific, evidence-based recommendations for medical professionals and to promote more standardized, effective and safe treatment for patients with PCNSL, a panel of experts from the Chinese Neurosurgical Society of the Chinese Medical Association and the Society of Hematological Malignancies of the Chinese Anti-Cancer Association jointly developed an evidence-based consensus. After comprehensively searching literature and conducting systematic reviews, two rounds of Delphi were conducted to reach consensus on the recommendations as follows: The histopathological specimens of PCNSL patients should be obtained as safely and comprehensively as possible by multimodal tomography-guided biopsy or minimally invasive surgery. Corticosteroids should be withdrawn from, or not be administered to, patients with suspected PCNSL before biopsy if the patient’s status permits. MRI (enhanced and DWI) should be performed for diagnosing and evaluating PCNSL patients where whole-body PET-CT be used at necessary time points. Mini-mental status examination can be used to assess cognitive function in the clinical management. Newly diagnosed PCNSL patients should be treated with combined high-dose methotrexate-based regimen and can be treated with a rituximab-inclusive regimen at induction therapy. Autologous stem cell transplantation can be used as a consolidation therapy. Refractory or relapsed PCNSL patients can be treated with ibrutinib with or without high-dose chemotherapy as re-induction therapy. Stereotactic radiosurgery can be used for PCNSL patients with a limited recurrent lesion who were refractory to chemotherapy and have previously received whole-brain radiotherapy. Patients with suspected primary vitreoretinal lymphoma (PVRL) should be diagnosed by vitreous biopsy. PVRL or PCNSL patients with concurrent VRL can be treated with combined systemic and local therapy.

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Orelabrutinib-bruton tyrosine kinase inhibitor-based regimens in the treatment of central nervous system lymphoma: a retrospective study

Cited by 24 publications

References 28 publications

Expression and Clinical Significance of Th1/Th2/Th17 Cytokines and Lymphocyte Subsets in PCNSL

Expression and Clinical Significance of Th1/Th2/Th17 Cytokines and Lymphocyte Subsets in PCNSL

Orelabrutinib Combined With Lenalidomide and Immunochemotherapy for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Retrospective Analysis of Case Series

Evidence-based expert consensus on the management of primary central nervous system lymphoma in China

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