Division of Hematology-Oncology, Mayo Clinic, Jacksonville, FL.
Division of Hematology/Oncology, University of Southern California Norris Cancer Center, Los Angeles, CA.
Clin Lymphoma Myeloma Leuk. 2019 Jan;19(1):29-34. doi: 10.1016/j.clml.2018.08.018. Epub 2018 Sep 5.
Despite therapeutic advancements that have significantly improved outcomes in multiple myeloma (MM), it remains an incurable disease. Patients with relapsed and/or refractory MM have an aggressive disease course, with inferior outcomes, necessitating the need for agents with novel therapeutic mechanisms. We present the results of a completed phase I trial of single-agent lorvotuzumab mertansine, a unique antibody-drug conjugate targeting CD56, which is frequently expressed in MM.
Thirty-seven patients with relapsed MM were enrolled in a dose-escalation phase I clinical trial to determine the maximum tolerated dose of lorvotuzumab mertansine (112 mg/m), followed by an expansion phase at the maximum tolerated dose.
Despite a high proportion of patients with relapsed and/or refractory MM (56.8%), stable disease or better was noted in 42.9% of patients, and these patients had a long duration of response (median, 15.5 months). The adverse event profile was favorable, with a low incidence of grade 3/4 adverse events and no infusion-related reactions. No humoral responses were detected against the study drug.
This completed phase I trial of single-agent lorvotuzumab mertansine provides ample evidence of safety and signals of clinical activity for this agent, warranting its further clinical development as part of combination regimens for the management of MM.
尽管在多发性骨髓瘤（MM）的治疗方面取得了显著进展，提高了患者的生存机会，但该病仍无法治愈。复发和/或难治性 MM 患者的疾病呈侵袭性发展，预后较差，因此需要采用具有新型治疗机制的药物。我们报告了单药洛莫司汀单抗治疗 MM 的 I 期临床试验结果，该药物是一种针对 CD56 的独特抗体药物偶联物，在 MM 中广泛表达。
37 例复发 MM 患者参加了 I 期剂量递增临床试验，以确定洛莫司汀单抗的最大耐受剂量（112mg/m），然后在最大耐受剂量下进行扩展阶段。
尽管大多数患者为复发和/或难治性 MM（56.8%），但仍有 42.9%的患者出现稳定疾病或更好的疗效，这些患者的缓解持续时间较长（中位数为 15.5 个月）。不良事件谱良好，3/4 级不良事件发生率低，无输液相关反应。未检测到针对研究药物的体液免疫反应。
这项洛莫司汀单抗单药治疗的 I 期临床试验提供了充分的安全性证据，并提示该药物具有临床活性，值得进一步开发为 MM 治疗的联合方案的一部分。
