Targeting Bruton Tyrosine Kinase for the Treatment of Vitreoretinal Lymphoma: Report of 11 Consecutive Patients

作者：Liang Wang, Wenxue Guan, Xindi Liu, Hong Wang, Xiaoyan Peng · 发表于：Blood · 年份：2021 · DOI：10.1182/blood-2021-144657 · 被引用次数：33 · 研究领域：CNS Lymphoma Diagnosis and Treatment、Lymphoma Diagnosis and Treatment、Chronic Lymphocytic Leukemia Research

Abstract Background: Vitreoretinal lymphoma (VRL) is a rare intraocular malignancy, which is regarded as a part of the central nervous system lymphoma (CNSL) and shows a close relationship with CNS progression. Currently, no standard treatment approaches have been defined yet, although intravitreal methotrexate with or without systemic chemotherapy are generally used. Bruton tyrosine kinase (BTK) is a vital effector molecule in the progress of B-cell proliferation. VRL, as well as PCNSL, display typically an activated B cell-like (ABC) phenotype of diffuse large B-cell lymphoma (DLBCL), with frequent CD79B and MYD88 mutations, which may represent a strong biological rationale for the use of BTK inhibitors. Previous studies have demonstrated that BTK inhibitors could penetrate the blood-brain barrier, and achieve 70-90% response rate in patients with PCNSL. However, whether BTK inhibitors could penetrate the blood-eye barrier and provide benefits to patients with VRL remains unknown. Methods: In this retrospective study, 11 consecutive patients with VRL were treated with BTK inhibitors monotherapy (zanubrutinib 160mg orally twice daily, or orelabrutinib 150mg orally daily), and they were intended to be treated for 2 years, or till disease progression, or unacceptable toxicity, whichever occurs first. All enrolled patients were pathologically confirmed as vitreoretinal DLBCL using vitreous biopsy, and PET-CT scan were performed to rule out the systemic involvement of lymphoma. ...