Division of Hematology and Oncology, University of Arizona School of Medicine, Tucson, AZ, USA.
Fargo VA Health Care System, Fargo, ND, USA.
Oncologist. 2024 Apr 4;29(4):278-288. doi: 10.1093/oncolo/oyad333.
The clinical efficacy of anti-CD20 radioimmunotherapy (RIT) is due to a combination of extracellular mechanisms involving immune-mediated cytotoxicity, and intracellular mechanisms related to inhibition of CD20 signaling and DNA damage from ionizing radiation. In 2002, the first RIT was approved by the U.S. Food and Drug Administration for the treatment of patients with indolent B-cell follicular non-Hodgkin lymphoma (NHL). The 2 approved agents, 90 Y-ibritumomab tiuxetan (90Y-IT, Zevalin, Acrotech Biopharma) and 131 I-tositumomab (131-IT, Bexxar, GlaxoSmithKline) both target CD20. The aim of this study was to review the clinical applications and supporting clinical trial data of anti-CD20 RIT for lymphoma.
A review of published articles and abstracts on the clinical efficacy and safety of 90Y-IT and iodine I 131 tositumomab was performed.
The clinical efficacy and safety of anti-CD20 RIT have been demonstrated in numerous clinical trials and case series. Agents have produced significant responses in patients with follicular NHLs and in off-label applications. Importantly, RIT has demonstrated promising findings in high-risk lymphomas and heavily pretreated and refractory patient populations. Associated toxicity profiles are noted as tolerable, acceptable, and most often reversible.
In the 2 decades since its approval, anti-CD20 RIT continues to demonstrate efficacy, particularly with a proportion of patients maintaining long-term remissions. The combination of prolonged efficacy, tolerability, and treatment convenience makes RIT a reasonable alternative to other systemic therapies. It is recommended that further research on RIT should focus on biomarkers of long-term response, pretargeting, and sequencing of RIT in the treatment course.
抗 CD20 放射免疫疗法(RIT)的临床疗效是由于细胞外机制(涉及免疫介导的细胞毒性)和细胞内机制(与 CD20 信号抑制和来自电离辐射的 DNA 损伤有关)的结合。2002 年,第一种 RIT 获得美国食品和药物管理局批准,用于治疗惰性 B 细胞滤泡性非霍奇金淋巴瘤(NHL)患者。批准的两种药物为 90Y-依替巴单抗替昔仑(90Y-IT,Zevalin,Acrotech Biopharma)和 131I-托西莫单抗(131-IT,Bexxar,葛兰素史克),均靶向 CD20。本研究旨在综述抗 CD20 RIT 在淋巴瘤中的临床应用及支持其临床研究数据。
对已发表的关于 90Y-IT 和碘 131 托西莫单抗临床疗效和安全性的文章和摘要进行了综述。
大量临床试验和病例系列研究证明了抗 CD20 RIT 的临床疗效和安全性。这些药物在滤泡性 NHL 患者和非适应证应用中产生了显著的反应。重要的是,RIT 在高危淋巴瘤和经大量预处理和难治性患者人群中显示出有前景的发现。相关毒性谱被认为是可耐受的、可接受的,且通常是可逆的。
自获得批准以来的 20 年中,抗 CD20 RIT 继续显示出疗效,特别是有一部分患者可长期缓解。疗效持久、耐受性好且治疗方便,使得 RIT 成为其他全身治疗的合理替代方案。建议进一步的 RIT 研究应侧重于长期反应的生物标志物、预靶向和 RIT 在治疗过程中的排序。