Engert A, Diehl V, Schnell R, Radszuhn A, Hatwig M T, Drillich S, Schön G, Bohlen H, Tesch H, Hansmann M L, Barth S, Schindler J, Ghetie V, Uhr J, Vitetta E
Klinik I fuer Innere Medizin, Universitaet zu Koeln, Germany.
Blood. 1997 Jan 15;89(2):403-10.
The anti-CD25 immunotoxin (IT), RFT5-SMPT-dgA, was used in a phase I dose escalation trial in patients with refractory Hodgkin's lymphoma. The IT was constructed by linking the monoclonal antibody RFT5 via a sterically hindered disulfide linker to deglycosylated ricin-A. All patients in this trial were heavily pretreated with a mean of 5 (range, 2 to 8) different prior therapies, including autologous bone marrow transplantation in 8 of 15. The mean age was 29 years (range, 19 to 34 years). Thirteen of 15 patients had advanced disease (stage IV) with massive tumor burdens and 6 of 15 had B symptoms. The IT was administered intravenously over 4 hours on days 1, 3, 5, and 7 for total doses per cycle of 5, 10, 15, or 20 mg/m2. Patients received one to four cycles of treatment. The peak serum concentration of intact IT varied from 0.2 to 9.7 micrograms/mL. The serum half life (T1/2) of the IT ranged from 4.0 to 10.5 hours (mean, 6.1 hours). Side effects were related to vascular leak syndrome (VLS), ie, decreases in serum albumin, edema, weight gain, hypotension, tachycardia, myalgia, and weakness. Two patients had a National Cancer Institute (NCI) grade 2 allergic reaction with generalized urticaria and mild bronchospasm. At 15 mg/m2, 1 patient experienced a grade 3 myalgia. All 3 patients receiving 20 mg/m2 experienced NCI grade 3 toxicities (edema, nausea, dyspnea or tachycardia) and 1 patient had NCI grade 4 myalgia. Thus, the maximal tolerated dose was 15 mg/m2. Seven of 15 patients made human antiricin antibodies (> or = 1.0 microgram/mL) and 6 of 15 developed human antimouse antibodies (> or = 1.0 microgram/mL). Clinical response included 2 partial remissions, 1 minor response, 3 stable diseases, and 9 progressive diseases. As has been predicted from the preclinical tests, these data seem to indicate clinical efficacy of this new IT in heavily pretreated Hodgkin's patients, thus warranting further clinical investigation.
抗CD25免疫毒素（IT）RFT5-SMPT-dgA用于难治性霍奇金淋巴瘤患者的I期剂量递增试验。该免疫毒素是通过将单克隆抗体RFT5经空间位阻二硫键连接至去糖基化蓖麻毒素A构建而成。本试验所有患者均接受过大量预处理，平均接受过5种（范围2至8种）不同的既往治疗，其中15例中有8例接受过自体骨髓移植。平均年龄为29岁（范围19至34岁）。15例患者中有13例患有晚期疾病（IV期），肿瘤负荷巨大，15例中有6例有B症状。免疫毒素在第1、3、5和7天静脉输注4小时，每个周期的总剂量为5、10、15或20mg/m²。患者接受1至4个周期的治疗。完整免疫毒素的血清峰值浓度在0.2至9.7μg/mL之间。免疫毒素的血清半衰期（T1/2）为4.0至10.5小时（平均6.1小时）。副作用与血管渗漏综合征（VLS）有关，即血清白蛋白降低、水肿、体重增加、低血压、心动过速、肌痛和虚弱。2例患者出现美国国立癌症研究所（NCI）2级过敏反应，伴有全身性荨麻疹和轻度支气管痉挛。在15mg/m²剂量时，1例患者出现3级肌痛。所有接受20mg/m²剂量的3例患者均出现NCI 3级毒性反应（水肿、恶心、呼吸困难或心动过速），1例患者出现NCI 4级肌痛。因此，最大耐受剂量为15mg/m²。15例患者中有7例产生人抗蓖麻毒素抗体（≥1.0μg/mL），15例中有6例产生人抗鼠抗体（≥1.0μg/mL）。临床反应包括2例部分缓解、1例轻微反应、3例病情稳定和9例病情进展。正如临床前试验所预测的那样，这些数据似乎表明这种新型免疫毒素在经过大量预处理的霍奇金病患者中具有临床疗效，因此值得进一步进行临床研究。
