Maeda T, Yamada Y, Tawara M, Yamasaki R, Yakata Y, Tsutsumi C, Onimaru Y, Kamihira S, Tomonaga M
Unit of General Medicine, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Japan.
Int J Hematol. 2001 Jul;74(1):70-5. doi: 10.1007/BF02982552.
Mantle cell lymphoma (MCL) has a poor prognosis without cure; the median overall survival ranges only from 3 to 4 years irrespective of conventional therapeutic regimens. IDEC-C2B8 (rituximab), a chimeric monoclonal antibody against the B-cell-specific antigen CD20, induces an evaluable clinical response in patients with MCL with mild toxicities. However, the single agent rituximab cannot cure MCL. Due to its low immunogenicity, an antibody against IDEC-C2B8 (human antichimeric antibody [HACA]) has rarely been produced in vivo. We report a patient with relapsed MCL who was successfully treated with IDEC-C2B8 for over a year although she developed HACA 6 months after the initial administration of IDEC-C2B8 in the phase II clinical trial conducted by Zenyaku Kogyo Co. Ltd. We followed the pharmacokinetics of IDEC-C2B8, the serum HACA titer, and the number of B lymphocytes in the peripheral blood in relation to clinical response. The HACA became undetectable soon after subsequent administrations of IDEC-C2B8. When the serum level of IDEC-C2B8 was kept elevated, clinical responses were apparently observed and HACA disappeared during this response period. There were no significant clinical toxicities related to the appearance of HACA. The present findings suggested that IDEC-C2B8 is effective and safe even in patients who have developed HACA.
套细胞淋巴瘤(MCL)预后不佳,无法治愈;无论采用何种传统治疗方案,其总生存期的中位数仅为3至4年。IDEC-C2B8(利妥昔单抗)是一种针对B细胞特异性抗原CD20的嵌合单克隆抗体,可在MCL患者中诱导出可评估的临床反应,且毒性轻微。然而,单药利妥昔单抗无法治愈MCL。由于其免疫原性低,体内很少产生针对IDEC-C2B8的抗体(人抗嵌合抗体[HACA])。我们报告了一名复发性MCL患者,在Zenyaku Kogyo有限公司进行的II期临床试验中,尽管在首次使用IDEC-C2B8 6个月后出现了HACA,但她接受IDEC-C2B8成功治疗了一年多。我们跟踪了IDEC-C2B8的药代动力学、血清HACA滴度以及外周血中B淋巴细胞数量与临床反应的关系。在随后使用IDEC-C2B8后不久,HACA就检测不到了。当IDEC-C2B8的血清水平持续升高时,明显观察到临床反应,且在此反应期内HACA消失。未观察到与HACA出现相关的明显临床毒性。目前的研究结果表明,即使在出现HACA的患者中,IDEC-C2B8也是有效且安全的。