Preliminary Evaluation of Zanubrutinib-Containing Regimens in DLBCL and the Cerebrospinal Fluid Distribution of Zanubrutinib: A 13-Case Series

Zhang, Yan; Li, Yanan; Zhuang, Zhe; Wang, Wei; Wang, Chong; Zhao, Dingxin; Zhou, Daobin

doi:10.3389/fonc.2021.760405

Cited by 33 publications

(33 citation statements)

References 32 publications

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“…The outcomes of CNS‐MCL are very poor (median survival <6 months). Ibrutinib and zanubrutinib have been shown to penetrate the blood–brain barrier 149,174 . A higher dose of ibrutinib (840 mg compared to 560 mg) improves the cerebrospinal fluid concentration in patients with CNS lymphoma.…”

Section: Special Considerationsmentioning

confidence: 99%

Mantle cell lymphoma in 2022—A comprehensive update on molecular pathogenesis, risk stratification, clinical approach, and current and novel treatments

Jain

Wang

2022

American J Hematol

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The field of mantle cell lymphoma (MCL) has witnessed remarkable progress due to relentless advances in molecular pathogenesis, prognostication, and newer treatments. MCL consists of a spectrum of clinical subtypes. Rarely, atypical cyclin D1-negative MCL and in situ MCL neoplasia are identified. Prognostication of MCL is further refined by identifying somatic mutations (such as TP53, NSD2, KMT2D), methylation status, chromatin organization pattern, SOX-11 expression, minimal residual disease (MRD), and genomic clusters. Lymphoid tissue microenvironment studies demonstrated the role of B-cell receptor signaling, nuclear factor kappa B (NF-kB), colony-stimulating factor (CSF)-1, the CD70-SOX-11 axis. Molecular mechanism of resistance, mutation dynamics, and pathogenic pathways (B-cell receptor (BCR), oxidative phosphorylation, and MYC) were identified in mediating resistance to various treatments (bruton tyrosine kinase (BTK) inhibitors [ibrutinib, acalabrutinib]. Treatment options range from conventional chemoimmunotherapy and stem cell transplantation (SCT) to targeted therapies against BTK (covalent and noncovalent), Bcl2, ROR1, cellular therapy such as anti-CD19 chimeric antigen receptor therapy (CAR-T), and most recently bispecific antibodies against CD19 and CD20. MCL patients frequently relapse. Complex pathogenesis and the management of patients with progression after treatment with BTK/Bcl2 inhibitors and CAR-T (triple-resistant MCL) remain a challenge. Next-generation clinical trials incorporating newer agents and concurrent translational and molecular investigations are ongoing. 1 | INTRODUCTION Mantle cell lymphoma (MCL) is an uncommon subtype of aggressive B cell non-Hodgkin's lymphoma (B-NHL). In 1982, Weisenburger et al. 1 first described 12 cases of malignant lymphoma with lymph node biopsies showing widened mantle zones around germinal centers in the secondary lymphoid follicles. The diagnosis of MCL 2 is now well characterized. MCL is no longer considered a single disease but is a mixed bag of various subcategories with a spectrum of molecular and clinical features. MCL patients have varied clinical presentations (generally symptomatic to an asymptomatic indolent clinical course).Advances in MCL research have significantly enhanced our understanding of pathogenesis, tumor microenvironment, 3 risk factor prognostication, 4 and molecular categories. 5 With the available treatment modalities (chemoimmunotherapy, 6 stem cell transplantation [SCT], 7 covalent and noncovalent BTK inhibitors, 8,9 bispecific antibodies, 10 an ROR1 drug conjugate, 11 and Bcl2 antagonists 12 ), the response rates and patient survival have improved. 13 The FDA approval of anti-CD19-chimeric antigen receptor therapy (CAR-T)-brexucabtagene autoleucel 14 -is a landmark

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Section: Special Considerationsmentioning

confidence: 99%

Mantle cell lymphoma in 2022—A comprehensive update on molecular pathogenesis, risk stratification, clinical approach, and current and novel treatments

Jain

Wang

2022

American J Hematol

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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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“…It should be noted that the ability of a BTKi to penetrate the blood–brain barrier renders it potentially effective in the treatment of patients with relapsed disease with central nervous system (CNS) involvement based on evidence showing that ibrutinib and zanubrutinib improved outcomes in these high-risk patients [ 27 – 29 ].…”

Section: Btk Inhibitors For R/r MCLmentioning

confidence: 99%

BTK Inhibitors and CAR T-Cell Therapy in Treating Mantle Cell Lymphoma—Finding a Dancing Partner

et al. 2022

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Purpose of Review This review focuses on the feasibility of combining Bruton’s tyrosine kinase (BTK) inhibitors (BTKis) with chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL). Potential scenarios for combination treatment with these agents are presented. Recent Findings BTKis and CAR T-cell therapy have revolutionized the treatment paradigm for R/R MCL. Ibrutinib, acalabrutinib, and zanubrutinib are covalent irreversible BTKis approved for R/R MCL. Brexucabtagene autoleucel was the first CAR T-cell therapy approved for R/R MCL based on findings from the ZUMA-2 trial. There is evidence to suggest that combination treatment with BTKis and CAR T-cell therapy may improve CAR T-cell efficacy. Summary As BTKis and CAR T-cell therapy become mainstays in R/R MCL therapy, combination treatment strategies should be evaluated for their potential benefit in R/R MCL.

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Preliminary Evaluation of Zanubrutinib-Containing Regimens in DLBCL and the Cerebrospinal Fluid Distribution of Zanubrutinib: A 13-Case Series

Cited by 33 publications

References 32 publications

Mantle cell lymphoma in 2022—A comprehensive update on molecular pathogenesis, risk stratification, clinical approach, and current and novel treatments

Mantle cell lymphoma in 2022—A comprehensive update on molecular pathogenesis, risk stratification, clinical approach, and current and novel treatments

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

BTK Inhibitors and CAR T-Cell Therapy in Treating Mantle Cell Lymphoma—Finding a Dancing Partner

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