Kaminski M S, Zasadny K R, Francis I R, Fenner M C, Ross C W, Milik A W, Estes J, Tuck M, Regan D, Fisher S, Glenn S D, Wahl R L
Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0724, USA.
J Clin Oncol. 1996 Jul;14(7):1974-81. doi: 10.1200/JCO.1996.14.7.1974.
The CD20 B-lymphocyte surface antigen expressed by 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 (131I) in 34 patients with B-cell lymphoma who had failed chemotherapy.
Patients were first given tracelabeled doses of 131I-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 131I 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 an infusion of 135 mg of unlabeled anti-B1 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.
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.
Nonmyeloablative radioimmunotherapy with 131I-anti-B1 is associated with a high rate of durable remissions in patients with B-cell lymphoma refractory to chemotherapy.
B细胞淋巴瘤所表达的CD20 B淋巴细胞表面抗原是放射免疫治疗（使用放射性标记抗体的治疗方法）的一个有吸引力的靶点。我们开展了一项I期剂量递增试验，以评估34例化疗失败的B细胞淋巴瘤患者使用非清髓剂量的碘-131（¹³¹I）标记的抗CD20单克隆抗体（抗B1）的毒性、肿瘤靶向性和疗效。
患者首先接受微量标记剂量的¹³¹I标记抗B1（15至20mg，5mCi）以评估放射性标记抗体的生物分布，然后接受放射免疫治疗剂量（15至20mg），该剂量标记的¹³¹I量将提供由微量剂量预测的特定厘戈瑞全身辐射剂量。全身辐射剂量在连续几组患者中从25cGy以10cGy的增量递增至85cGy。为了评估放射性标记抗体的生物分布是否可以优化，最初的患者在连续几周内额外接受一或两个微量剂量，每个剂量之前分别在一周输注135mg未标记的抗B1，下一周输注685mg。导致最优化微量生物分布的未标记抗体剂量也在放射免疫治疗剂量之前给予。后来的患者在输注685mg未标记的抗B1之前接受单个微量剂量和放射免疫治疗剂量。
治疗耐受性良好。血液学毒性是剂量限制性的，75cGy被确定为最大耐受全身辐射剂量。28例患者接受了34至161mCi的放射免疫治疗剂量，14例患者完全缓解，8例部分缓解。13例低度淋巴瘤患者均有反应，10例完全缓解。8例转化型淋巴瘤患者中有6例有反应。19例对其最后一个化疗疗程耐药的患者中有13例以及所有化疗敏感疾病患者均有反应。完全缓解的中位持续时间超过16.5个月。6例患者在治疗后16至31个月仍处于完全缓解状态。
¹³¹I-抗B1非清髓放射免疫治疗与化疗难治性B细胞淋巴瘤患者的高持久缓解率相关。
