Orelabrutinib Combined With Lenalidomide and Immunochemotherapy for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Retrospective Analysis of Case Series
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) c...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.901797/full |
| _version_ | 1818465698751447040 |
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| author | Chuanwei Yang Chuanwei Yang Chuanwei Yang Yong Cui Yong Cui Xiaohui Ren Xiaohui Ren Ming Li Ming Li Kefu Yu Shaoping Shen Shaoping Shen Haihui Jiang Haihui Jiang Haihui Jiang Mingxiao Li Mingxiao Li Xiaokang Zhang Xiaokang Zhang Xuzhe Zhao Xuzhe Zhao Qinghui Zhu Qinghui Zhu Song Lin Song Lin Song Lin |
| author_facet | Chuanwei Yang Chuanwei Yang Chuanwei Yang Yong Cui Yong Cui Xiaohui Ren Xiaohui Ren Ming Li Ming Li Kefu Yu Shaoping Shen Shaoping Shen Haihui Jiang Haihui Jiang Haihui Jiang Mingxiao Li Mingxiao Li Xiaokang Zhang Xiaokang Zhang Xuzhe Zhao Xuzhe Zhao Qinghui Zhu Qinghui Zhu Song Lin Song Lin Song Lin |
| author_sort | Chuanwei Yang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T20:48:04Z |
| format | Article |
| id | doaj.art-6f814cd31284489bab8e761408cf54f4 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T20:48:04Z |
| publishDate | 2022-06-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-6f814cd31284489bab8e761408cf54f42022-12-22T02:30:36ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-06-011210.3389/fonc.2022.901797901797Orelabrutinib Combined With Lenalidomide and Immunochemotherapy for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Retrospective Analysis of Case SeriesChuanwei Yang0Chuanwei Yang1Chuanwei Yang2Yong Cui3Yong Cui4Xiaohui Ren5Xiaohui Ren6Ming Li7Ming Li8Kefu Yu9Shaoping Shen10Shaoping Shen11Haihui Jiang12Haihui Jiang13Haihui Jiang14Mingxiao Li15Mingxiao Li16Xiaokang Zhang17Xiaokang Zhang18Xuzhe Zhao19Xuzhe Zhao20Qinghui Zhu21Qinghui Zhu22Song Lin23Song Lin24Song Lin25Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou University, Henan, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Peking University Third Hospital, Peking University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaBeijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaNational Clinical Research Center for Neurological Diseases, Center of Brain Tumor, Beijing Key Laboratory of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, ChinaBackgroundRelapsed/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.https://www.frontiersin.org/articles/10.3389/fonc.2022.901797/fullOrelabrutinibsafetyefficacyrelapsed/refractoryprimary central nervous system lymphomagenomic characteristics |
| spellingShingle | Chuanwei Yang Chuanwei Yang Chuanwei Yang Yong Cui Yong Cui Xiaohui Ren Xiaohui Ren Ming Li Ming Li Kefu Yu Shaoping Shen Shaoping Shen Haihui Jiang Haihui Jiang Haihui Jiang Mingxiao Li Mingxiao Li Xiaokang Zhang Xiaokang Zhang Xuzhe Zhao Xuzhe Zhao Qinghui Zhu Qinghui Zhu Song Lin Song Lin Song Lin Orelabrutinib Combined With Lenalidomide and Immunochemotherapy for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Retrospective Analysis of Case Series Frontiers in Oncology Orelabrutinib safety efficacy relapsed/refractory primary central nervous system lymphoma genomic characteristics |
| title | Orelabrutinib Combined With Lenalidomide and Immunochemotherapy for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Retrospective Analysis of Case Series |
| title_full | Orelabrutinib Combined With Lenalidomide and Immunochemotherapy for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Retrospective Analysis of Case Series |
| title_fullStr | Orelabrutinib Combined With Lenalidomide and Immunochemotherapy for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Retrospective Analysis of Case Series |
| title_full_unstemmed | Orelabrutinib Combined With Lenalidomide and Immunochemotherapy for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Retrospective Analysis of Case Series |
| title_short | Orelabrutinib Combined With Lenalidomide and Immunochemotherapy for Relapsed/Refractory Primary Central Nervous System Lymphoma: A Retrospective Analysis of Case Series |
| title_sort | orelabrutinib combined with lenalidomide and immunochemotherapy for relapsed refractory primary central nervous system lymphoma a retrospective analysis of case series |
| topic | Orelabrutinib safety efficacy relapsed/refractory primary central nervous system lymphoma genomic characteristics |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.901797/full |
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