Marshalek Joseph P, Qing Xin, Dragan Marcin, Tomassetti Sarah
Division of Hematology and Medical Oncology, Department of Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA.
Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA, USA.
J Hematol. 2024 Dec;13(6):268-277. doi: 10.14740/jh1341. Epub 2024 Dec 2.
CD20-targeted therapies are widely used in the management of B-cell lymphomas. Re-treatment with CD20-directed agents is common; however, previous research has demonstrated loss of CD20 expression at relapse in a subset of patients.
In this single-center retrospective cohort of 243 patients, CD20 analysis was performed by immunohistochemistry (IHC) and/or flow cytometry at diagnosis and at relapse if a biopsy was performed.
Of 109 patients with relapsed or refractory B-cell lymphoma, 59 patients with CD20-positive lymphoma at diagnosis underwent a biopsy at relapse for a total of 76 biopsies across all relapses. The rate of partial or complete CD20 expression loss was 11.9% (four patients with partial loss, three patients with complete loss). There were four cases of CD20 loss at first relapse (three IHC, one flow cytometry), two at second relapse (one IHC, one IHC and flow cytometry), and one at fifth relapse (IHC and flow cytometry). CD20 antigen escape was observed in marginal zone lymphoma, follicular lymphoma, and diffuse large B-cell lymphoma (DLBCL). All patients with CD20 expression loss previously received rituximab. Among patients with CD20 antigen escape, 85.7% had stage IV disease, and median overall survival after CD20 loss was 4 months. In the group of five patients with indolent lymphoma and CD20 expression loss, three patients (60%) had concurrent transformation to high-grade lymphoma.
This study, which reinforces the importance of repeating a biopsy at relapse before implementing CD20-directed therapy, is particularly relevant given the widespread use of rituximab along with the emerging significance of CD20-targeted bispecific antibodies in the management of B-cell lymphomas.
CD20靶向治疗广泛应用于B细胞淋巴瘤的治疗。使用CD20导向药物进行再治疗很常见;然而,先前的研究表明,一部分患者在复发时会出现CD20表达缺失。
在这个包含243例患者的单中心回顾性队列研究中,在诊断时以及复发时(如果进行了活检)通过免疫组织化学(IHC)和/或流式细胞术进行CD20分析。
在109例复发或难治性B细胞淋巴瘤患者中,59例诊断时CD20阳性淋巴瘤患者在复发时进行了活检,所有复发共进行了76次活检。部分或完全CD20表达缺失率为11.9%(4例部分缺失,3例完全缺失)。首次复发时出现4例CD20缺失(3例通过IHC,1例通过流式细胞术),第二次复发时出现2例(1例通过IHC,1例通过IHC和流式细胞术),第五次复发时出现1例(通过IHC和流式细胞术)。在边缘区淋巴瘤、滤泡性淋巴瘤和弥漫性大B细胞淋巴瘤(DLBCL)中观察到CD20抗原逃逸。所有CD20表达缺失的患者之前都接受过利妥昔单抗治疗。在CD20抗原逃逸的患者中,85.7%患有IV期疾病,CD20缺失后的中位总生存期为4个月。在5例惰性淋巴瘤且CD20表达缺失的患者组中,3例(60%)同时转化为高级别淋巴瘤。
鉴于利妥昔单抗的广泛使用以及CD20靶向双特异性抗体在B细胞淋巴瘤治疗中日益重要的意义,本研究强调了在实施CD20导向治疗前复发时重复活检的重要性。