Phase I immunotoxin trial in patients with B-cell lymphoma.
Phase I immunotoxin trial in patients with B-cell lymphoma.
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发表时间：
1991-08
期刊：
影响因子：
11.2
通讯作者：
E. Vitetta;M. Stone;P. Amlot;J. Fay;R. May;M. Till;J. Newman;Patty Clark;R. Collins;D. Cunningham;V. Ghetie;J. Uhr;P. Thorpe
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作者：
E. Vitetta;M. Stone;P. Amlot;J. Fay;R. May;M. Till;J. Newman;Patty Clark;R. Collins;D. Cunningham;V. Ghetie;J. Uhr;P. Thorpe
在I期剂量递增临床试验中，15例难治性B细胞淋巴瘤患者接受了一种高效免疫毒素的治疗，该毒素由抗CD22单抗(RFB4)的Fab‘片段与化学去糖基化的蓖麻毒素A链结合而成。所有患者均为低、中、高度非霍奇金淋巴瘤。静脉注射免疫毒素。间隔48小时，分两次至六次。血药浓度峰值和t1/2无剂量依赖性，平均分别为1.3微克/毫升和86分钟。3例抗A链抗体，1例同时抗A链抗体和小鼠免疫球蛋白抗体。3名患者的抗体反应较低(小于或等于85微克/毫升)，直到治疗后1个月才能检测到。免疫毒素的最大耐受量为75 mg/m2。剂量相关的毒性包括血管渗漏综合征、发热、食欲不振和肌痛。剂量限制性毒性包括肺水肿和/或渗出、表达失语症和横纹肌溶解(导致可逆性肾功能衰竭)。没有证据表明有肝功能障碍。在可评估的患者中，38%的患者获得了部分缓解，在CD22+肿瘤细胞超过50%的患者中，50%的患者实现了部分缓解。临床反应与肿瘤分级无关，一般为一过性反应，持续1~4个月。
Fifteen patients with refractory B-cell lymphoma were treated in a Phase I dose escalation clinical trial with a highly potent immunotoxin consisting of the Fab' fragment of a monoclonal anti-CD22 antibody (RFB4) coupled to chemically deglycosylated ricin A chain. All patients had low, intermediate, or high grade non-Hodgkin's lymphoma. The immunotoxin was administered i.v. in two to six doses at 48-h intervals. The peak serum concentration and the t1/2 were not dose dependent among patients and averaged 1.3 micrograms/ml and 86 min, respectively. Three patients made antibody against A chain, and a fourth made antibody against both A chain and mouse immunoglobulin. Antibody responses were low (less than or equal to 85 micrograms/ml) in three patients and were not detected until 1 mo after treatment. The maximum tolerated dose of the immunotoxin was 75 mg/m2. Dose-related toxicities included vascular leak syndrome, fever, anorexia, and myalgia. Dose-limiting toxicities included pulmonary edema and/or effusion, expressive aphasia, and rhabdomyolysis (resulting in reversible kidney failure). There was no evidence of liver dysfunction. Partial responses were achieved in 38% of evaluable patients, and in those patients who had greater than 50% CD22+ tumor cells, 50% of the patients achieved a partial response. Clinical responses were not related to tumor grade and were generally transient, lasting between 1 and 4 mo.