Zelenetz Andrew D
Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Semin Oncol. 2003 Apr;30(2 Suppl 4):22-30. doi: 10.1053/sonc.2003.23803.
The majority of patients with non-Hodgkin's lymphoma (NHL) who respond to conventional chemotherapy will relapse and eventually become refractory to chemotherapy. Each subsequent remission is typically of similar or shorter duration than the last. Recent developments in radioimmunotherapy using monoclonal antibodies to specifically target malignant B cells have yielded promising results in relapsed and refractory NHL patients. The radiolabeled anti-CD20 antibody tositumomab and iodine 131 tositumomab (Bexxar; Corixa Corp, South San Francisco, CA and GlaxoSmithKline, Philadelphia, PA) has been shown to be safe and effective in the treatment of patients with relapsed low-grade (indolent) NHL. Objective responses were achieved in 57% to 71% of patients in phase I to phase III trials, and remission durations were significantly longer in the phase III trial compared with the last remission induced by chemotherapy. In addition, tositumomab and iodine I 131 tositumomab was shown to be effective in the subset analysis of patients with transformed low-grade NHL, which is particularly resistant to conventional therapies. The incidence of transient, nonhematologic adverse events was low and mainly mild to moderate in severity. Hematologic toxicity is the major dose-limiting toxicity associated with radioimmunotherapy; however, patient-specific dosimetry maintained hematologic toxicity within predictable, transient, and manageable limits in the phase II and phase III trials of tositumomab and iodine I 131 tositumomab. Although approximately 10% of patients treated with tositumomab and iodine I 131 tositumomab developed human-antimouse antibodies, treatment with tositumomab does not preclude the administration of subsequent chimeric antibody therapies. In conclusion, these studies show that tositumomab and iodine I 131 tositumomab treatment is safe and induces high response rates and durable remissions in heavily pretreated patients with low-grade or transformed low-grade NHL.
大多数对传统化疗有反应的非霍奇金淋巴瘤（NHL）患者会复发，最终对化疗产生耐药。随后的每次缓解期通常与上一次相似或更短。利用单克隆抗体特异性靶向恶性B细胞的放射免疫疗法的最新进展，在复发和难治性NHL患者中取得了有希望的结果。放射性标记的抗CD20抗体托西莫单抗和碘131托西莫单抗（Bexxar；Corixa公司，加利福尼亚州南旧金山和葛兰素史克公司，宾夕法尼亚州费城）已被证明在治疗复发的低度（惰性）NHL患者中是安全有效的。在I期至III期试验中，57%至71%的患者获得了客观缓解，与化疗诱导的上一次缓解相比，III期试验中的缓解期明显更长。此外，托西莫单抗和碘I 131托西莫单抗在转化型低度NHL患者的亚组分析中显示有效，这类患者对传统疗法尤其耐药。短暂的非血液学不良事件发生率较低，严重程度主要为轻度至中度。血液学毒性是与放射免疫疗法相关的主要剂量限制性毒性；然而，在托西莫单抗和碘I 131托西莫单抗的II期和III期试验中，针对患者的剂量测定将血液学毒性维持在可预测、短暂且可控的范围内。尽管接受托西莫单抗和碘I 131托西莫单抗治疗的患者中约有10%产生了人抗鼠抗体，但使用托西莫单抗治疗并不排除随后使用嵌合抗体疗法。总之，这些研究表明，托西莫单抗和碘I 131托西莫单抗治疗对于经过大量预处理的低度或转化型低度NHL患者是安全的，可诱导高缓解率和持久缓解。
