RADIOLABELED-ANTIBODY THERAPY OF B-CELL LYMPHOMA WITH AUTOLOGOUS BONE-MARROW SUPPORT
RADIOLABELED-ANTIBODY THERAPY OF B-CELL LYMPHOMA WITH AUTOLOGOUS BONE-MARROW SUPPORT
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DOI：
10.1056/nejm199310213291702
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发表时间：
1993-10-21
影响因子：
158.5
通讯作者：
BERNSTEIN, ID
中科院分区：
文献类型：
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作者：
PRESS, OW;EARY, JF;BERNSTEIN, ID
背景识别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潜在有效的淋巴瘤新疗法。我们评估了碘-131标记的抗CD 20（B1和1F 5）和抗CD 37（MB-1）抗体在43例复发性B细胞淋巴瘤患者中的生物分布、毒性和疗效。使用递增剂量的抗体（0.5、2.5和10 mg/kg体重）进行序贯生物分布研究，所述抗体用5至10 mCi的I-131进行示踪标记。肿瘤和正常器官吸收的辐射剂量通过连续γ照相机成像和肿瘤活检来估计。估计肿瘤接受的辐射剂量大于肝、肺或肾的患者（即，具有良好生物分布的患者）符合I-131标记抗体治疗性输注的条件。24例患者具有良好的生物分布，19例接受了234至777 mCi的I-131标记抗体（58至1168 mg）的治疗性输注，随后进行自体骨髓回输，结果16例完全缓解，2例部分缓解，1例轻微缓解（肿瘤消退25%至50%）。9名患者已持续完全缓解3至53个月。毒性反应包括骨髓抑制、恶心、感染和两次心肺毒性发作，在接受I-131标记抗体治疗的患者中，毒性反应为中度，其正常器官剂量低于27.25戈伊。在抗体生物分布良好的B细胞淋巴瘤患者中，使用I-131标记抗体的高剂量放射免疫治疗与高应答率相关。
Background. 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.Methods. 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 I-131. 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 I-131-labeled antibodies according to a phase 1 dose-escalation protocol.Results. Twenty-four patients had a favorable biodistribution, and 19 received therapeutic infusions of 234 to 777 mCi of I-131-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 I-131-labeled antibodies that delivered less than 27.25 Gy to normal organs.Conclusions. High-dose radioimmunotherapy with I-131-labeled antibodies is associated with a high response rate in patients with B-cell lymphoma in whom antibody biodistribution is favorable.