Ansell Stephen M, Horwitz Steven M, Engert Andreas, Khan Khuda Dad, Lin Thomas, Strair Roger, Keler Tibor, Graziano Robert, Blanset Diann, Yellin Michael, Fischkoff Steven, Assad Albert, Borchmann Peter
Division of Hematology, Mayo Clinic School of Medicine, Rochester, MN 55905, USA.
J Clin Oncol. 2007 Jul 1;25(19):2764-9. doi: 10.1200/JCO.2006.07.8972. Epub 2007 May 21.
MDX-060 is a human anti-CD30 immunoglobulin (Ig) G1kappa monoclonal antibody that inhibits growth of CD30-expressing tumor cells in preclinical models. To determine the safety, maximum-tolerated dose (MTD), and efficacy of MDX-060 in patients with relapsed or refractory CD30+ lymphomas, sequential phase I and II studies were performed.
In the phase I portion, MDX-060 was administered intravenously at doses of 0.1, 1, 5, or 10 mg/kg weekly for 4 weeks to cohorts of three to six patients. Twenty-one patients--16 with Hodgkin's lymphoma (HL), three with anaplastic large-cell lymphoma (ALCL), and two with CD30+ T-cell lymphoma--were enrolled. Because of the lack of a defined MTD or dose-response correlation, the phase II portion was amended to include several dose levels. In the phase II portion, an additional 51 patients, 47 with HL and four with ALCL, were treated at doses of 1, 5, 10, and 15 mg/kg.
MDX-060 was well tolerated, and an MTD has not been identified. Only 7% of patients experienced grade 3 or 4 treatment-related adverse events. Among the 72 patients treated, clinical responses were observed in six. Twenty-five patients had stable disease, including five who remained free from progression 1 year after treatment.
MDX-060 was well tolerated at doses up to 15 mg/kg. MDX-060 has limited activity as a single agent, but the minimal toxicity observed and the significant proportion of patients with stable disease suggests that further study of MDX-060 in combination with other therapies is warranted.
MDX - 060是一种人抗CD30免疫球蛋白（Ig）G1κ单克隆抗体，在临床前模型中可抑制表达CD30的肿瘤细胞生长。为确定MDX - 060在复发或难治性CD30 +淋巴瘤患者中的安全性、最大耐受剂量（MTD）及疗效，进行了序贯的I期和II期研究。
在I期研究中，将MDX - 060以0.1、1、5或10 mg/kg的剂量静脉注射，每周1次，共4周，每组3至6名患者。共纳入21例患者，其中16例为霍奇金淋巴瘤（HL），3例为间变性大细胞淋巴瘤（ALCL），2例为CD30 + T细胞淋巴瘤。由于未确定MTD或剂量反应相关性，II期研究部分进行了修订，纳入多个剂量水平。在II期研究中，另外51例患者（47例HL和4例ALCL）接受了1、5、10和15 mg/kg剂量的治疗。
MDX - 060耐受性良好，尚未确定MTD。仅7%的患者出现3级或4级治疗相关不良事件。在接受治疗的72例患者中，观察到6例有临床反应。25例患者病情稳定，其中5例在治疗1年后仍无疾病进展。
MDX - 060在高达15 mg/kg的剂量下耐受性良好。MDX - 060作为单一药物活性有限，但观察到的毒性极小且有相当比例的患者病情稳定，提示有必要进一步研究MDX - 060与其他疗法联合应用的情况。
