TREATMENT OF REFRACTORY NON-HODGKINS LYMPHOMA WITH RADIOLABELED MB-1 (ANTI-CD37) ANTIBODY
TREATMENT OF REFRACTORY NON-HODGKINS LYMPHOMA WITH RADIOLABELED MB-1 (ANTI-CD37) ANTIBODY
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DOI：
10.1200/jco.1989.7.8.1027
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发表时间：
1989-08-01
影响因子：
45.3
通讯作者：
BERNSTEIN, ID
中科院分区：
文献类型：
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作者：
PRESS, OW;EARY, JF;BERNSTEIN, ID
在10例常规治疗失败的晚期、低度或中度非霍奇金淋巴瘤患者中评价了碘131（131 I）标记的抗CD 37单克隆抗体（MoAb）MB-1的生物分布、毒性和治疗潜力。使用递增量的用5至10 mCi 131 I示踪标记的抗体MB-1（0.5、2.5、10 mg/kg）进行连续剂量测定研究。连续肿瘤活检和γ照相机成像显示，10 mg/kg MoAb剂量在研究的10名患者中产生最佳MoAb生物分布。对5名脾肿大和肿瘤负荷> 1 kg的患者进行的生物分布研究表明，并非所有肿瘤部位都比正常器官接受更多的辐射，因此这些患者未接受高剂量放射免疫治疗。其他5名患者没有脾肿大，肿瘤负荷< 0.5 kg;该组中的所有5名患者均显示MoAb优先定位和保留在肿瘤部位。其中4例患者接受了与抗CD 37单克隆抗体MB-1结合的131 I（232至608 mCi）治疗，向肿瘤部位输送850至4，260戈伊。这四名患者中的每一名都达到了完全的肿瘤缓解（持续4、6、11+和8+个月）。第5例患者的肿瘤不表达CD 37抗原，用131 I标记的抗CD 20 MoAb 1F 5治疗，并获得部分缓解。所有病例均在治疗后3 ~ 5周出现骨髓抑制，但无其他明显急性毒性。正常的B细胞从血流中短暂耗尽，但免疫球蛋白（IG）水平不受影响，也没有发生严重的感染。两名患者需要回输先前储存的自体净化骨髓。2例患者在治疗后1年出现无症状甲状腺功能减退症。可耐受的毒性和令人鼓舞的疗效保证了在该I期试验中进一步的剂量递增。
The biodistribution, toxicity, and therapeutic potential of anti-CD37 monoclonal antibody (MoAb) MB-1 labeled with iodine 131 (131I) was evaluated in ten patients with advanced-, low- or intermediate-grade non-Hodgkin''s lymphomas who failed conventional treatment. Sequential dosimetric studies were performed with escalating amounts of antibody MB-1 (0.5, 2.5, 10 mg/kg) trace-labeled with 5 to 10 mCi 131I. Serial tumor biopsies and gamma camera imaging showed that the 10 mg/kg MoAb dose yielded the best MoAb biodistribution in the ten patients studied. Biodistribution studies in the five patients with splenomegaly and tumor burdens > 1 kg indicated that not all tumor sites would receive more radiation than normal organs, and these patients were therefore not treated with high-dose radioimmunotherapy. The other five patients did not have splenomegaly and had tumor burdens < 0.5 kg; all five patients in this group showed preferential localization and retention of MoAb at tumor sites. Four of these patients have been treated with 131I (232 to 608 mCi) conjugated to anti-CD37 MoAb MB-1, delivering 850 to 4,260 Gy to tumor sites. Each of these four patients attained a complete tumor remission (lasting 4, 6, 11+, and 8+ months). A fifth patient, whose tumor did not express the CD37 antigen, was treated with 131I-labeled anti-CD20 MoAb 1F5 and achieved a partial response. Myelosuppression occurred 3 to 5 weeks after treatment in all cases, but there were no other significant acute toxicities. Normal B cells were transiently depleted from the bloodstream, but immunoglobulin (Ig) levels were not affected, and no serious infections occurred. Two patients require reinfusion of previously stored autologous, purged bone marrow. Two patients developed asymptomatic hypothyroidism 1 year after therapy. The tolerable toxicity and encouraging efficacy warrant further dose escalation in this phase I trial.