Center for Drug Evaluation and Research, U.S. Food and Drug Administration.
Clin Cancer Res. 2018 Jul 15;24(14):3242-3246. doi: 10.1158/1078-0432.CCR-17-3179. Epub 2018 Feb 23.
On September 1, 2017, the FDA granted approval for gemtuzumab ozogamicin (Mylotarg; Pfizer Inc.) in combination with daunorubicin and cytarabine and as a monotherapy for the treatment of adult patients with newly diagnosed CD33-positive acute myeloid leukemia (AML). Gemtuzumab ozogamicin is a CD33-targeted antibody-drug conjugate joined to calicheamicin. Approval of gemtuzumab ozogamicin combination treatment was based on a randomized trial of 271 patients with newly diagnosed AML treated with daunorubicin and cytarabine with or without 3 mg/m fractionated gemtuzumab ozogamicin, which resulted in an event-free survival (EFS) of 13.6 months for gemtuzumab ozogamicin + daunorubicin and cytarabine and 8.8 months for daunorubicin and cytarabine alone [HR = 0.68 (95% confidence interval (CI), 0.51-0.91)]. Hemorrhage, prolonged thrombocytopenia, and veno-occlusive disease were serious toxicities that were more common in patients treated with gemtuzumab ozogamicin + daunorubicin and cytarabine. Approval of gemtuzumab ozogamicin monotherapy was based on a randomized trial of 237 patients with newly diagnosed AML treated without curative intent. Median overall survival (OS) was 4.9 months with gemtuzumab ozogamicin versus 3.6 months on best supportive care [HR = 0.69 (95% CI, 0.53-0.90)]. Adverse events were similar on both arms. Postapproval, several studies are required including evaluation of fractionated gemtuzumab ozogamicin pharmacokinetics, safety of combination gemtuzumab ozogamicin in the pediatric population, immunogenicity, and the effects of gemtuzumab ozogamicin on platelet function. .
2017 年 9 月 1 日，美国食品药品监督管理局（FDA）批准吉妥珠单抗奥佐米星（Mylotarg；辉瑞公司）与柔红霉素和阿糖胞苷联合使用，并作为一种单药疗法用于治疗新诊断的 CD33 阳性急性髓细胞性白血病（AML）成人患者。吉妥珠单抗奥佐米星是一种靶向 CD33 的抗体-药物偶联物，与加利车霉素相连。吉妥珠单抗奥佐米星联合治疗的批准是基于一项随机试验的结果，该试验纳入了 271 例新诊断的 AML 患者，他们接受柔红霉素和阿糖胞苷治疗，联合或不联合 3mg/m 分次给予吉妥珠单抗奥佐米星，结果显示，吉妥珠单抗奥佐米星+柔红霉素和阿糖胞苷组的无事件生存（EFS）为 13.6 个月，而单用柔红霉素和阿糖胞苷组为 8.8 个月[风险比（HR）=0.68（95%置信区间（CI），0.51-0.91)]。出血、血小板减少延长和静脉阻塞性疾病是接受吉妥珠单抗奥佐米星+柔红霉素和阿糖胞苷治疗的患者更常见的严重毒性反应。吉妥珠单抗奥佐米星单药治疗的批准是基于一项随机试验的结果，该试验纳入了 237 例未经根治性治疗的新诊断 AML 患者。吉妥珠单抗奥佐米星组的中位总生存（OS）为 4.9 个月，最佳支持治疗组为 3.6 个月[HR=0.69（95%CI，0.53-0.90)]。两个治疗组的不良事件相似。批准后，需要开展几项研究，包括评估分次给予吉妥珠单抗奥佐米星的药代动力学、儿童人群中联合使用吉妥珠单抗奥佐米星的安全性、免疫原性，以及吉妥珠单抗奥佐米星对血小板功能的影响。
