McLaughlin P, Grillo-López A J, Link B K, Levy R, Czuczman M S, Williams M E, Heyman M R, Bence-Bruckler I, White C A, Cabanillas F, Jain V, Ho A D, Lister J, Wey K, Shen D, Dallaire B K
Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
J Clin Oncol. 2023 Jan 10;41(2):154-162. doi: 10.1200/JCO.22.02403.
The CD20 antigen is expressed on more than 90% of B-cell lymphomas. It is appealing for targeted therapy, because it does not shed or modulate. A chimeric monoclonal antibody more effectively mediates host effector functions and is itself less immunogenic than are murine antibodies.
This was a multiinstitutional trial of the chimeric anti-CD20 antibody, IDEC-C2B8. Patients with relapsed low grade or follicular lymphoma received an outpatient treatment course of IDEC-C2B8 375 mg/m2 intravenously weekly for four doses.
From 31 centers, 166 patients were entered. Of this intent-to-treat group, 48% responded. With a median follow-up duration of 11.8 months, the projected median time to progression for responders is 13.0 months. Serum antibody levels were sustained longer after the fourth infusion than after the first, and were higher in responders and in patients with lower tumor burden. The majority of adverse events occurred during the first infusion and were grade 1 or 2; fever and chills were the most common events. Only 12% of patients had grade 3 and 3% grade 4 toxicities. A human antichimeric antibody was detected in only one patient.
The response rate of 48% with IDEC-C2B8 is comparable to results with single-agent cytotoxic chemotherapy. Toxicity was mild. Attention needs to be paid to the rate of antibody infusion, with titration according to toxicity. Further investigation of this agent is warranted, including its use in conjunction with standard chemotherapy.
CD20抗原在90%以上的B细胞淋巴瘤中表达。由于其不会脱落或调节，因此对靶向治疗具有吸引力。与鼠源抗体相比，嵌合单克隆抗体能更有效地介导宿主效应功能，且自身免疫原性更低。
这是一项关于嵌合抗CD20抗体IDEC-C2B8的多机构试验。复发的低度或滤泡性淋巴瘤患者接受门诊治疗，静脉注射IDEC-C2B8 375mg/m²，每周一次，共四剂。
来自31个中心的166例患者入组。在这个意向性治疗组中，48%的患者有反应。中位随访时间为11.8个月，反应者预计的中位疾病进展时间为13.0个月。第四次输注后血清抗体水平维持时间比第一次输注后更长，且反应者和肿瘤负荷较低的患者血清抗体水平更高。大多数不良事件发生在第一次输注期间，为1级或2级；发热和寒战是最常见的事件。只有12%的患者出现3级毒性，3%的患者出现4级毒性。仅在一名患者中检测到人类抗嵌合抗体。
IDEC-C2B8的48%的反应率与单药细胞毒性化疗的结果相当。毒性较轻。需要注意抗体输注速度，并根据毒性进行滴定。有必要对该药物进行进一步研究，包括其与标准化疗联合使用。
