用[131I]抗B1（抗CD20）抗体对B细胞淋巴瘤进行放射免疫治疗。

Radioimmunotherapy of B-cell lymphoma with [131I]anti-B1 (anti-CD20) antibody.

作者信息

Kaminski M S, Zasadny K R, Francis I R, Milik A W, Ross C W, Moon S D, Crawford S M, Burgess J M, Petry N A, Butchko G M

机构信息

Division of Hematology, University of Michigan, Ann Arbor.

出版信息

N Engl J Med. 1993 Aug 12;329(7):459-65. doi: 10.1056/NEJM199308123290703.

DOI:10.1056/NEJM199308123290703

PMID:7687326

Abstract

BACKGROUND

Many patients with non-Hodgkin's lymphomas are not cured by current therapies, and new approaches to treatment are needed. As part of an ongoing phase 1 study, we examined the effect of radioimmunotherapy with 131I-labeled B-cell-specific anti-CD20 monoclonal antibody in 10 patients with CD20-positive B-cell lymphomas in whom primary chemotherapy had failed.

METHODS AND RESULTS

Anti-B1 (anti-CD20) mouse monoclonal antibody trace-labeled with 131I (15 mg containing 5 mCi) was given intravenously at approximately one-week intervals: first, without pretreatment with unlabeled anti-B1 antibody, to all 10 patients; then, with pretreatment with 135 mg of unlabeled antibody, to 8 patients; and then, with pretreatment with 685 mg, to 2 patients. Serial quantitative gamma-camera images and measures of whole-body radioactivity were obtained after each tracer dose. All known disease sites larger than 2 cm could be imaged. The effect of a pretreatment dose of unlabeled anti-B1 antibody on targeting of the tumor with the radiolabeled antibody was variable. The pretreatment dose of unlabeled antibody that produced the highest ratio of the tumor dose to the whole-body dose in tracer studies was then used to deliver higher doses of radioactivity for radioimmunotherapy in nine patients. Three patients received doses designed to deliver 25 cGy to the whole body (two patients treated twice, six to eight weeks apart), four patients received 35 cGy (one patient treated twice), and two patients received 45 cGy (one patient treated twice); each dose contained 34 to 66 mCi of activity. Six of the nine treated patients had tumor responses, including patients with bulky or chemotherapy-resistant disease: four patients had complete remissions, and two had partial responses. Three patients had objective responses to tracer infusions before they received radioimmunotherapeutic doses. Of the four patients with complete remissions, one remained in remission for eight months and the other three continue to have no disease progression (for 11, 9, and 8 months). There was mild or no myelosuppression.

CONCLUSIONS

Radioimmunotherapy with [131I]anti-B1 antibody is a promising new treatment for lymphoma.

摘要

背景

许多非霍奇金淋巴瘤患者无法通过目前的治疗方法治愈，因此需要新的治疗方法。作为一项正在进行的1期研究的一部分，我们研究了用131I标记的B细胞特异性抗CD20单克隆抗体进行放射免疫治疗对10例原发性化疗失败的CD20阳性B细胞淋巴瘤患者的疗效。

方法与结果

用131I（15mg含5mCi）微量标记的抗B1（抗CD20）小鼠单克隆抗体以大约一周的间隔静脉注射：首先，在未用未标记的抗B1抗体预处理的情况下，对所有10例患者进行注射；然后，在使用135mg未标记抗体预处理后，对8例患者进行注射；接着，在使用685mg未标记抗体预处理后，对2例患者进行注射。每次注射示踪剂后，获取连续的定量γ相机图像和全身放射性测量值。所有大于2cm的已知疾病部位都可以成像。未标记的抗B1抗体预处理剂量对放射性标记抗体靶向肿瘤的影响各不相同。然后，在示踪剂研究中产生肿瘤剂量与全身剂量最高比值的未标记抗体预处理剂量被用于对9例患者进行更高剂量的放射免疫治疗。3例患者接受的剂量旨在使全身接受25cGy（2例患者分两次治疗，间隔6至8周），4例患者接受35cGy（1例患者分两次治疗），2例患者接受45cGy（1例患者分两次治疗）；每个剂量含有34至66mCi的活性。9例接受治疗的患者中有6例出现肿瘤反应，包括肿块较大或对化疗耐药的患者：4例患者完全缓解，2例患者部分缓解。3例患者在接受放射免疫治疗剂量之前对示踪剂输注有客观反应。在4例完全缓解的患者中，1例缓解持续了8个月，另外3例继续无疾病进展（分别为11、9和8个月）。有轻度或无骨髓抑制。