Press O W, Eary J F, Appelbaum F R, Martin P J, Badger C C, Nelp W B, Glenn S, Butchko G, Fisher D, Porter B
Department of Medicine, University of Washington, Seattle.
N Engl J Med. 1993 Oct 21;329(17):1219-24. doi: 10.1056/NEJM199310213291702.
Radiolabeled monoclonal antibodies recognizing B-lymphocyte surface antigens represent a potentially effective new therapy for lymphomas. We assessed the biodistribution, toxicity, and efficacy of anti-CD20 (B1 and 1F5) and anti-CD37 (MB-1) antibodies labeled with iodine-131 in 43 patients with B-cell lymphoma in relapse.
Sequential biodistribution studies were performed with escalating doses of antibody (0.5, 2.5, and 10 mg per kilogram of body weight) trace-labeled with 5 to 10 mCi of 131I. The doses of radiation absorbed by tumors and normal organs were estimated by serial gamma-camera imaging and tumor biopsies. Patients whose tumors were estimated to receive greater doses of radiation than the liver, lungs, or kidneys (i.e., patients with a favorable biodistribution) were eligible for therapeutic infusion of 131I-labeled antibodies according to a phase 1 dose-escalation protocol.
Twenty-four patients had a favorable biodistribution, and 19 received therapeutic infusions of 234 to 777 mCi of 131I-labeled antibodies (58 to 1168 mg) followed by autologous marrow reinfusion, resulting in complete remission in 16, a partial response in 2, and a minor response (25 to 50 percent regression of tumor) in 1. Nine patients have remained in continuous complete remission for 3 to 53 months. Toxic effects included myelosuppression, nausea, infections, and two episodes of cardiopulmonary toxicity, and were moderate in patients treated with doses of 131I-labeled antibodies that delivered less than 27.25 Gy to normal organs.
High-dose radioimmunotherapy with 131I-labeled antibodies is associated with a high response rate in patients with B-cell lymphoma in whom antibody biodistribution is favorable.
识别B淋巴细胞表面抗原的放射性标记单克隆抗体代表了一种对淋巴瘤潜在有效的新疗法。我们评估了131碘标记的抗CD20（B1和1F5）及抗CD37（MB-1）抗体在43例复发B细胞淋巴瘤患者中的生物分布、毒性和疗效。
采用递增剂量的抗体（每公斤体重0.5、2.5和10毫克）进行连续生物分布研究，抗体用5至10毫居里的131I进行微量标记。通过连续的γ相机成像和肿瘤活检估计肿瘤和正常器官吸收的辐射剂量。根据1期剂量递增方案，那些估计肿瘤接受的辐射剂量高于肝脏、肺或肾脏的患者（即生物分布良好的患者）有资格接受131I标记抗体的治疗性输注。
24例患者生物分布良好，19例接受了234至777毫居里131I标记抗体（58至1168毫克）的治疗性输注，随后进行自体骨髓回输，16例完全缓解，2例部分缓解，1例有轻微反应（肿瘤缩小25%至50%）。9例患者持续完全缓解3至53个月。毒性作用包括骨髓抑制、恶心、感染以及两例心肺毒性，在接受131I标记抗体剂量且正常器官接受辐射剂量小于27.25戈瑞的患者中，毒性作用为中度。
对于抗体生物分布良好的B细胞淋巴瘤患者，高剂量131I标记抗体放射免疫疗法有较高的缓解率。
