Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA
Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Oncologist. 2018 Sep;23(9):1103-1108. doi: 10.1634/theoncologist.2017-0604. Epub 2018 Apr 12.
On September 2, 2017, the U.S. Food and Drug Administration approved gemtuzumab ozogamicin (GO; Mylotarg; Pfizer, New York City, NY) for treatment of relapsed or refractory (R/R) CD33-positive acute myeloid leukemia (AML) in patients 2 years of age and older. GO is a CD33-directed antibody drug conjugate linked to the cytotoxic antibiotic calicheamicin. It originally received accelerated approval for treatment of older patients with relapsed CD33-positive AML in 2000, but it was withdrawn from the market in 2010 when the confirmatory trial failed to demonstrate clinical benefit among safety concerns, such as a higher rate of induction fatalities on the GO combination arm compared with chemotherapy alone. In addition, GO was associated with hepatic veno-occlusive disease (VOD), which has substantial morbidity and mortality. Pharmacokinetic analyses suggested a lower maximum concentration of GO would result in less VOD without affecting target saturation or efficacy. A meta-analysis across dose schedules of GO in patients with R/R AML showed that a lower-dose "fractionated" schedule of 3 mg/m days 1, 4, and 7 was associated with less early mortality, hemorrhage, and VOD, without an apparent decrease in complete remission (CR) rate. MyloFrance 1 was a single-arm study evaluating response rates in patients with relapsed CD33-positive AML treated with the lower-dose fractionated GO regimen. The CR rate was 26% (95% confidence interval 16%-40%). Common adverse reactions were fever, infections, nausea, vomiting, constipation, bleeding, increased liver enzymes, and mucositis. There were no cases of VOD. These results supported the approval of GO as monotherapy for R/R CD33-positive AML using the lower-dose fractionated regimen.
Gemtuzumab ozogamicin (GO) 3 mg/m days 1, 4, and 7 is an active regimen for induction of remission when used to treat patients with relapsed or refractory CD33-positive acute myeloid leukemia without curative intent. The risks of hepatic veno-occlusive disease and early mortality with this regimen appear to be lower than reported previously for GO 9 mg/m days 1 and 15. The data were not sufficient to enable conclusions about the safety of GO in children younger than 2 years of age.
2017 年 9 月 2 日，美国食品药品监督管理局批准吉妥珠单抗奥佐米星（GO；Mylotarg；辉瑞，纽约，NY）用于治疗 2 岁及以上复发或难治性（R/R）CD33 阳性急性髓细胞白血病（AML）患者。GO 是一种靶向 CD33 的抗体药物偶联物，与细胞毒性抗生素 calicheamicin 相连。它最初于 2000 年因治疗复发的 CD33 阳性 AML 老年患者而获得加速批准，但由于安全性问题，包括与单独化疗相比，GO 联合治疗组诱导死亡率更高，该确认试验未能证明临床获益，该药于 2010 年撤出市场。此外，GO 与肝静脉闭塞性疾病（VOD）有关，后者具有较高的发病率和死亡率。药代动力学分析表明，较低的 GO 最大浓度会导致更少的 VOD，而不会影响目标饱和度或疗效。一项针对 R/R AML 患者 GO 不同剂量方案的荟萃分析显示，较低剂量的“分段”方案（3 mg/m 天 1、4 和 7）与早期死亡率、出血和 VOD 减少相关，而完全缓解（CR）率无明显下降。MyloFrance 1 是一项单臂研究，评估了接受较低剂量分段 GO 方案治疗的复发 CD33 阳性 AML 患者的反应率。CR 率为 26%（95%置信区间 16%-40%）。常见的不良反应包括发热、感染、恶心、呕吐、便秘、出血、肝酶升高和黏膜炎。无 VOD 病例。这些结果支持使用较低剂量的分段方案，批准 GO 作为复发或难治性 CD33 阳性 AML 的单药治疗。
吉妥珠单抗奥佐米星（GO）3 mg/m 天 1、4 和 7 是一种用于治疗无治愈意图的复发或难治性 CD33 阳性急性髓细胞白血病患者的诱导缓解的有效方案。与 GO 9 mg/m 天 1 和 15 相比，该方案治疗患者的肝静脉闭塞性疾病和早期死亡率风险似乎较低。数据不足以得出关于 2 岁以下儿童使用 GO 的安全性结论。
