Clinical outcomes of newly diagnosed primary CNS lymphoma treated with ibrutinib‐based combination therapy: A real‐world experience of off‐label ibrutinib use

Chen, Feili; Pang, Diwen; Guo, Hanguo; Ou, Qiuxiang; Wu, Xue; Jiang, Xingshan; Wei, Xiaojuan; Liu, Sichu; Huang, Ling; Liang, Zhongming; Zhou, Dong; Li, Wenyu

doi:10.1002/cam4.3499

Cited by 32 publications

(42 citation statements)

References 37 publications

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“…For 31 articles, the full text was reviewed and 23 of them were excluded for following reasons: conference abstract (n = 11), other drugs (n = 3), other diseases (n = 3), review (n = 4), update of results (n = 2). The eight remaining studies fulfilled the eligibility criteria and were included in the meta/analysis and included three prospective cohort studies (11)(12)(13) and four retrospective studies (14)(15)(16)(17)(18). The literature review and identification process are shown in Figure 1.…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

“…The literature review and identification process are shown in Figure 1. The meta/analysis evaluated the efficacy and toxicity of the ibrutinib regimen for a total of 162 patients with CNSL across eight cohort studies (11)(12)(13)(14)(15)(16)(17)(18). The age of the patients ranged from 18 to 87 years, with a male predominance (58.64%).…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

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Efficacy and Safety of Ibrutinib in Central Nervous System Lymphoma: A PRISMA-Compliant Single-Arm Meta-Analysis

Sun

et al. 2021

Front. Oncol.

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BackgroundCentral nervous system lymphoma (CNSL) is an aggressive lymphoma. Studies investigating primary CNSL determined that the Bruton tyrosine kinase (BTK) played an important role in pathogenesis. Ibrutinib, an oral BTK inhibitor, is a new treatment strategy for CNSL. The purpose of this meta-analysis was to clarify the effectiveness and safety of ibrutinib in the treatment of CNSL.MethodsA systematic search of PubMed, Embase, Cochrane library, Wanfang Data Knowledge Service Platform, and China National Knowledge Infrastructure databases was conducted through to 31 October 2019. Studies involving patients with CNSL who received ibrutinib that reported the overall response (OR), complete remission (CR), and partial response (PR) were included. The random-effects or fixed-effects model with double arcsine transformation was used for the pooled rates and 95% confidence intervals (CI) were determined for all outcomes.ResultsEight studies including 162 patients were identified and included in the meta-analysis. The pooled OR rate after treatment with ibrutinib was 69% (95% CI, 61–79%, I2 = 47.57%, p = 0.06), while the pooled CR and PR was 52% (95% CI, 35–68%, I2 = 74.95%, p = 0.00) and 17% (95% CI, 7–30%, I2 = 67.85%, p = 0.00), respectively. Among PCNSL patients, including new diagnoses PCNSL and R/R PCNSL, the pooled OR rate was 72% (95% CI, 63–80%, I2 = 49.20%, p = 0.06) while the pooled CR and PR rates were 53% (95% CI, 33–73%, I2 = 75.04%, p = 0.00) and 22% (95% CI, 14–30%, I2 = 46.30%, p = 0.07), respectively. Common adverse events above grade 3 included cytopenia and infections.ConclusionsThe ibrutinib-containing therapy was well tolerated and offered incremental benefit to patients with CNSL. However, randomized-controlled studies that directly compare efficacy and adverse events of ibrutinib are still needed.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42020218974.

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Section: Study Selection and Characteristicsmentioning

confidence: 99%

Section: Study Selection and Characteristicsmentioning

confidence: 99%

Efficacy and Safety of Ibrutinib in Central Nervous System Lymphoma: A PRISMA-Compliant Single-Arm Meta-Analysis

Sun

et al. 2021

Front. Oncol.

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“…Analysis of gene mutations such as CD79B and MYD88 in CSF can be used as a molecular diagnostic method for PCNSL (10). The longitudinal analysis of CSF ctDNA revealed that sustained tumor responses were associated with the clearance of ctDNA from the CSF (98,99). CSF ctDNA predicted central nervous system relapse in central nervous system and systemic lymphomas (97).…”

Section: Discussionmentioning

confidence: 99%

Clinical Application of Liquid Biopsy in Non-Hodgkin Lymphoma

Liu

2021

Front. Oncol.

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Non-Hodgkin lymphoma (NHL) is a common type of hematological malignant tumor, composed of multiple subtypes that originate from B lymphocytes, T lymphocytes, and natural killer cells. A diagnosis of NHL depends on the results of a pathology examination, which requires an invasive tissue biopsy. However, due to their invasive nature, tissue biopsies have many limitations in clinical applications, especially in terms of evaluating the therapeutic response and monitoring tumor progression. To overcome these limitations of traditional tissue biopsies, a technique known as “liquid biopsies” (LBs) was proposed. LBs refer to noninvasive examinations that can provide biological tumor data for analysis. Many studies have shown that LBs can be broadly applied to the diagnosis, treatment, prognosis, and monitoring of NHL. This article will briefly review various LB methods that aim to improve NHL management, including the evaluation of cell-free DNA/circulating tumor DNA, microRNA, and tumor-derived exosomes extracted from peripheral blood in NHL.

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“…However, another ibrutinib-based regimen combined with HD-MTX did show an increased 80% (12/15) response in r/r patients [ 72 ]. Recently, a real-world experience of combining ibrutinib with HD-MTX in treating ND PCNSL patients reported 81.8% of ORR with mind tolerable anemia, hypoalbuminemia and hypokalemia, indicating a potential role of BTKi in the frontline treatment [ 73 ]. A couple of BTKi-based trials evaluating ibrutinib, acalabritinb or orelabrutinib in combination with the agents HD-MTX, R-MVP, MRE, lenalidomide or an anti-programmed death (PD)-1 antibody are currently ongoing (Table 5 ).…”

Section: Novel Targeted Therapies and Emerging Agentsmentioning

confidence: 99%

Current and emerging therapies for primary central nervous system lymphoma

et al. 2021

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Primary central nervous system (CNS) lymphoma (PCNSL) is a rare type of extranodal lymphoma exclusively involving the CNS at the onset, with diffuse large B-cell lymphoma (DLBCL) as the most common histological subtype. As PCNSL is a malignancy arising in an immune-privileged site, suboptimal delivery of systemic agents into tumor tissues results in poorer outcomes in PCNSL than in non-CNS DLBCLs. Commonly used regimens for PCNSL include high-dose methotrexate-based chemotherapy with rituximab for induction therapy and intensive chemotherapy followed by autologous hematopoietic stem cell transplantation or whole-brain radiotherapy for consolidation therapy. Targeted agents against the B-cell receptor signaling pathway, microenvironment immunomodulation and blood-brain barrier (BBB) permeabilization appear to be promising in treating refractory/relapsed patients. Chimeric antigen receptor-T cells (CAR-T cells) have been shown to penetrate the BBB as a potential tool to manipulate this disease entity while controlling CAR-T cell-related encephalopathy syndrome. Future approaches may stratify patients according to age, performance status, molecular biomarkers and cellular bioinformation. This review summarizes the current therapies and emerging agents in clinical development for PCNSL treatment.

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Clinical outcomes of newly diagnosed primary CNS lymphoma treated with ibrutinib‐based combination therapy: A real‐world experience of off‐label ibrutinib use

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 32 publications

References 37 publications

Efficacy and Safety of Ibrutinib in Central Nervous System Lymphoma: A PRISMA-Compliant Single-Arm Meta-Analysis

Efficacy and Safety of Ibrutinib in Central Nervous System Lymphoma: A PRISMA-Compliant Single-Arm Meta-Analysis

Clinical Application of Liquid Biopsy in Non-Hodgkin Lymphoma

Current and emerging therapies for primary central nervous system lymphoma

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