Martin Peter, Furman Richard R, Rutherford Sarah, Ruan Jia, Ely Scott, Greenberg June, Coleman Morton, Goldsmith Stanley J, Leonard John P
a Department of Medicine , Weill Cornell Medical College , New York , NY , USA.
b Pathology and Laboratory Medicine, Weill Cornell Medical College , New York , NY , USA.
Leuk Lymphoma. 2015;56(11):3065-70. doi: 10.3109/10428194.2015.1028052. Epub 2015 May 12.
Milatuzumab (hLL1), a humanized anti-CD74 monoclonal antibody, has activity in preclinical non-Hodgkin lymphoma (NHL) models. We conducted a phase 1 trial in previously treated B-cell malignancies. Dose escalation included four planned dose levels (1.5, 4, 6 and 8 mg/kg) with milatuzumab given twice weekly for 6 weeks. After dose level 1, the schedule was changed to daily (Monday-Friday) for 10 days. Twenty-two patients were treated. The most common possibly related toxicities were infusion reaction, anemia, lymphopenia, neutropenia and thrombocytopenia. Three patients experienced dose-limiting toxicity (neutropenia, neutropenia, rash) at dose levels 1, 2 and 4, respectively. Eight patients had stable disease, with no objective responses. The serum half-life of milatuzumab was ∼2 h. In seven patients, In-111 imaging showed no clear evidence of tumor targeting. The short half-life may reflect CD74 rapid internalization and presence on extratumoral tissues; this antigen sink must be overcome to capitalize on the promising preclinical activity of the drug.
米拉图单抗（hLL1）是一种人源化抗CD74单克隆抗体，在临床前非霍奇金淋巴瘤（NHL）模型中具有活性。我们对先前接受过治疗的B细胞恶性肿瘤患者进行了1期试验。剂量递增包括四个计划剂量水平（1.5、4、6和8mg/kg），米拉图单抗每周给药两次，共6周。在第1剂量水平之后，给药方案改为每日（周一至周五）给药，持续10天。共治疗了22例患者。最常见的可能相关毒性为输注反应、贫血、淋巴细胞减少、中性粒细胞减少和血小板减少。三名患者分别在第1、2和4剂量水平出现剂量限制性毒性（中性粒细胞减少、中性粒细胞减少、皮疹）。八名患者病情稳定，无客观缓解。米拉图单抗的血清半衰期约为2小时。在七名患者中，铟-111显像未显示明显的肿瘤靶向证据。短半衰期可能反映了CD74的快速内化以及在肿瘤外组织中的存在；必须克服这种抗原库，才能利用该药物有前景的临床前活性。
