A phase I study of an anti-CD22-deglycosylated ricin A chain immunotoxin in the treatment of B-cell lymphomas resistant to conventional therapy.
A phase I study of an anti-CD22-deglycosylated ricin A chain immunotoxin in the treatment of B-cell lymphomas resistant to conventional therapy.
复制标题
DOI：
10.1182/blood.v82.9.2624.bloodjournal8292624
复制
发表时间：
1993-11
期刊：
影响因子：
20.3
通讯作者：
P. Amlot;M. Stone;D. Cunningham;J. Fay;J. Newman;R. Collins;R. May;M. McCarthy;J. Richardson;V. Ghetie
中科院分区：
文献类型：
--
作者：
P. Amlot;M. Stone;D. Cunningham;J. Fay;J. Newman;R. Collins;R. May;M. McCarthy;J. Richardson;V. Ghetie
26例患者，其B细胞淋巴瘤复发后，常规治疗，在I期剂量递增研究与免疫毒素组成的小鼠CD 22单克隆抗体（RFB 4：IgG 1 K）耦合到化学去糖基化蓖麻毒素A链（dgA）。每隔48小时静脉输注2至12剂免疫毒素。血清峰浓度和半衰期（T1/2）与剂量无直接相关性，平均值分别为3.8 μ g/mL和7.8小时。主要的剂量限制性毒性是由血管渗漏综合征（VLS）引起的，包括体重增加、水肿、血清白蛋白降低，以及严重的肺水肿。肌痛频繁发生，仅在1例发生横纹肌溶解的患者中发生剂量限制。血液中淋巴瘤细胞的存在（>或= 10（10）/L）和临床可检测到的脾肿大与毒性降低和T1/2缩短相关。24例可评价患者中有9例（37.5%）产生小鼠IG或dgA抗体。有5例部分缓解（PR）和1例完全缓解（CR），持续30至78天。血清中免疫毒素的高峰浓度、长T1/2和大曲线下面积（AUC）与临床反应和毒性相关。三名CD 5+淋巴瘤患者（包括两名CLL患者）中没有一名对免疫毒素有超过轻度的毒性或反应。
Twenty-six patients, whose B-cell lymphoma had relapsed after conventional therapies, were treated in a phase I dose escalation study with an immunotoxin consisting of a mouse CD22 monoclonal antibody (RFB4:IgG1K) coupled to chemically deglycosylated ricin A chain (dgA). Two to 12 doses of the immunotoxin were infused intravenously at 48-hour intervals. The peak serum concentration and half-life (T1/2) did not correlate directly with the dose and averaged 3.8 micrograms/mL and 7.8 hours, respectively. The main dose-limiting toxicity was caused by the vascular leak syndrome (VLS) consisting of weight gain, edema, serum albumin decrease, and critically by pulmonary edema. Myalgia occurred frequently and was only dose limiting in one patient who developed rhabdomyolysis. The presence of lymphoma cells in the blood (> or = 10(10)/L) and clinically detectable splenomegaly were associated with reduced toxicity and a shorter T1/2. Nine of 24 evaluable patients (37.5%) made antibody to either mouse Ig or dgA. There were five partial responses (PR) and one complete response (CR) lasting 30 to 78 days. High peak concentrations of immunotoxin in the serum, a long T1/2, and large areas under the curve (AUC) correlated with both clinical response and toxicity. None of three patients with CD5+ lymphomas (including two CLL patients) had more than mild toxicity or responded to the immunotoxin.