Department of Medicine, New York Presbyterian Hospital-Cornell Medical Center, New York, NY, USA.
Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medical College, New York Presbyterian Hospital-Cornell Medical Center, New York, NY, USA.
Onco Targets Ther. 2014 Jun 18;7:1095-100. doi: 10.2147/OTT.S49480. eCollection 2014.
Multiple myeloma is the second most common hematologic malignancy in the US. Treatments utilizing alkylating agents, corticosteroids, proteasome inhibitors, and immunomodulatory drugs have resulted in significant survival benefits, however, despite the advances, relapse is inevitable. Decreased depth and duration of response obtained with each successive relapse of disease is typical of the disease course, thereby highlighting a continuing need for new treatment options. With the introduction of monoclonal antibodies for multiple myeloma, new options for treatment in the relapsed setting are on the horizon. Among the new immunologic agents is daratumumab (DARA), a humanized antibody to CD38 with potent multifaceted antitumor activity. Phase I and II clinical trials have demonstrated significant reduction in serum M-protein and bone marrow plasma cell percentage in refractory patients, with an acceptable toxicity profile. Moreover, ex vivo studies have shown that DARA may be particularly useful in combination with currently used anti-myeloma agents. With a recent breakthrough drug designation by the US Food and Drug Administration, DARA shows promise as mono- and combination therapy for the treatment of relapsed/refractory multiple myeloma.
在美国，多发性骨髓瘤是第二常见的血液系统恶性肿瘤。利用烷化剂、皮质类固醇、蛋白酶体抑制剂和免疫调节剂进行治疗已经显著提高了患者的生存率，然而，尽管取得了这些进展，疾病的复发仍然是不可避免的。随着疾病的每次复发，所获得的反应深度和持续时间都会减少，这是疾病进程的典型特征，因此，持续需要新的治疗选择。随着多发性骨髓瘤单克隆抗体的引入，复发患者的治疗新选择即将出现。在新的免疫制剂中，有一种是达雷妥尤单抗（DARA），这是一种针对 CD38 的人源化抗体，具有强大的多方面抗肿瘤活性。I 期和 II 期临床试验表明，在难治性患者中，血清 M 蛋白和骨髓浆细胞百分比显著降低，且具有可接受的毒性特征。此外，体外研究表明，DARA 与目前使用的抗骨髓瘤药物联合使用可能特别有用。最近，美国食品和药物管理局（FDA）给予了突破性药物指定，这表明 DARA 有望成为治疗复发性/难治性多发性骨髓瘤的单一药物和联合治疗药物。
