Iodine-131 - Anti-B1 radioimmunotherapy for B-cell lymphoma
Iodine-131 - Anti-B1 radioimmunotherapy for B-cell lymphoma
复制标题
DOI：
10.1200/jco.1996.14.7.1974
复制
发表时间：
1996-07-01
影响因子：
45.3
通讯作者：
Wahl, RL
中科院分区：
文献类型：
--
作者：
Kaminski, MS;Zasadny, KR;Wahl, RL
目的：表达CD 20 B淋巴细胞表面抗原的B细胞淋巴瘤是放射免疫治疗的有吸引力的靶点，使用放射性标记抗体进行治疗。我们进行了一项I期剂量递增试验，以评估非清髓剂量的碘-131（I-131）标记的抗CD 20单克隆抗体（抗B1）在34例化疗失败的B细胞淋巴瘤患者中的毒性、肿瘤靶向和疗效。患者首先给予微量标记剂量的I-131标记的抗B1（15至20 mg，5 mCi），以评估放射性标记抗体的生物分布，然后用一定量的I-131标记放射免疫剂量（15至20 mg），该剂量将提供由示踪剂剂量预测的特定厘戈瑞剂量的全身辐射。在连续的患者组中，全身辐射剂量从25 cGy递增至85 cGy，增量为10 cGy。为了评估放射性标记的抗体生物分布是否可以优化，在连续几周内给予初始患者一个或两个额外的示踪剂剂量，每个剂量之前一周输注135 mg未标记的抗Si，下一周输注685 mg。在放射免疫剂量之前，还给予了导致最佳示踪剂生物分布的未标记抗体剂量。随后患者接受单次示踪剂和放射免疫剂量，然后输注685 mg未标记的抗B1。结果：治疗耐受性良好。血液学毒性是剂量限制性的，75 cGy被确定为全身最大耐受辐射剂量。28例患者接受了34至161 mCi的放射免疫剂量，导致14例患者完全缓解，8例患者部分缓解。所有13例低度恶性淋巴瘤患者均缓解，10例完全缓解。8例转化型淋巴瘤患者中有6例缓解。19例对最后一个疗程化疗耐药的患者中有13例和所有化疗敏感性疾病患者均出现应答。完全缓解的中位持续时间超过16.5个月。6例患者在完全缓解16至31个月后treatment.Conclusion：非清髓性放射免疫治疗与I-131-抗B1与持久缓解率高，化疗难治性B细胞淋巴瘤患者。
Purpose: The CD20 B-lymphocyte surface antigen expressed B-cell lymphomas is an attractive target for radioimmunotherapy, treatment using radiolabeled antibodies. We conducted a phase I dose-escalation trial to assess the toxicity, tumor targeting, and efficacy of nonmyeloablative doses of an anti-CD20 monoclonal antibody (anti-B1) labeled with iodine-131 (I-131) in 34 patients with B-cell lymphoma who herd failed chemotherapy.Patients and Methods: Patients were first given trace-labeled doses of I-131-labeled anti-B1 (15 to 20 mg, 5 mCi) to assess radiolabeled antibody biodistribution, and then a radioimmunotherapeutic dose(15 to 20 mg) labeled with a quantity of I-131 that would deliver a specified centigray dose of whole-body radiation predicted by the tracer dose. Whole-body radiation doses were escalated from 25 to 85 cGy in sequential groups of patients in 10-cGy increments. To evaluate if radiolabeled antibody biodistribution could be optimized, initial patients were given one or two additional tracer doses on successive weeks, each dose preceded by on infusion of 135 mg of unlabeled anti-Si one week and 685 mg the next. The unlabeled antibody dose resulting in the most optimal tracer biodistribution was also given before the radioimmunotherapeutic dose. Later patients were given a single tracer dose and radioimmunotherapeutic dose preceded by infusion of 685 mg of unlabeled anti-B1.Results: Treatment was well tolerated. Hematologic toxicity was dose-limiting, and 75 cGy was established as the maximally tolerated whole-body radiation dose. Twenty-eight patients received radioimmunotherapeutic doses of 34 to 161 mCi, resulting in complete remission in 14 patients and a partial response in eight. All 13 patients with low-grade lymphoma responded, and 10 achieved a complete remission. Six of eight patients with transformed lymphoma responded. Thirteen of 19 patients whose disease was resistant to their last course of chemotherapy and all patients with chemotherapy-sensitive disease responded. The median duration of complete remission exceeds 16.5 months. Six patients remain in complete remission 16 to 31 months after treatment.Conclusion: Nonmyeloablative radioimmunotherapy with I-131-anti-B1 is associated with a high rate of durable remissions in patients with B-cell lymphoma refractory to chemotherapy.