Blinatumomab for Acute Lymphoblastic Leukemia: The First Bispecific T-Cell Engager Antibody to Be Approved by the EMA for Minimal Residual Disease
Blinatumomab for Acute Lymphoblastic Leukemia: The First Bispecific T-Cell Engager Antibody to Be Approved by the EMA for Minimal Residual Disease
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DOI：
10.1634/theoncologist.2019-0559
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发表时间：
2020-04-01
期刊：
影响因子：
5.8
通讯作者：
Pignatti, Francesco
中科院分区：
文献类型：
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作者：
Ali, Sahra;Moreau, Alexandre;Pignatti, Francesco
2018年11月15日，人用药品委员会（CHMP）建议扩大blinatumomab的适应症，包括治疗患有微小残留病（MRD）阳性B细胞前体急性淋巴细胞白血病（ALL）的成人。 Blinatumomab 被授权用于治疗复发或难治性 B 前体 ALL，此次变更涉及扩大使用范围。 2018年3月29日，美国食品药品监督管理局（FDA）加速批准blinatumomab用于治疗处于缓解期但仍存在MRD的B细胞前体ALL成人和儿童。 2018 年 7 月 26 日，CHMP 最初对延期采取了否定意见。最初拒绝的原因是，尽管blinatumomab有助于减少许多患者残留癌细胞的数量，但没有强有力的证据表明它可以提高生存率。复审期间，CHMP 咨询了科学顾问组。 CHMP 同意专家组的结论，即虽然没有强有力的证据表明患者寿命更长，但主要研究 (MT103-203) 的可用数据表明对 blinatumomab 具有良好的持久反应，主要终点完整分析集的总体完全缓解率（定义为在基线建立的中心实验室进行 Ig 或 T 细胞受体聚合酶链反应 MRD 检测的最低要求灵敏度为 1 x 10(-4) 的所有受试者 [n = 113]）为 79.6%（90/113；95% 置信区间，71.0-86.6），完成 MRD 反应的中位时间为 29.0 天（范围，5-71）。因此，CHMP 得出结论，blinatumomab 的益处大于其风险，并建议批准营销授权变更。孤儿药委员会经过重新评估后，认为继续获得显着益处，并建议维持孤儿药资格，从而保持 10 年市场独占性（孤儿药资格是一项法律程序，允许在首次用于人体之前或在临床开发期间指定具有治疗罕见疾病潜力的药物）。该药品的营销授权持有者是 Amgen Europe B.V。blinatumomab 的实践免疫治疗具有优异且可持续的效果，为微小残留病阳性急性淋巴细胞白血病（一种预后不良的疾病）患者带来了新的希望。详细介绍了针对该患者群体的治疗的新建议和实践改变。
On November 15, 2018, the Committee for Medicinal Products for Human Use (CHMP) recommended the extension of indication for blinatumomab to include the treatment of adults with minimal residual disease (MRD) positive B-cell precursor acute lymphoblastic leukemia (ALL). Blinatumomab was authorized to treat relapsed or refractory B-precursor ALL, and the change concerned an extension of use. On March 29, 2018, the U.S. Food and Drug Administration (FDA) granted accelerated approval to blinatumomab to treat both adults and children with B-cell precursor ALL who are in remission but still have MRD. On July 26, 2018, the CHMP had originally adopted a negative opinion on the extension. The reason for the initial refusal was that although blinatumomab helped to reduce the amount of residual cancer cells in many patients, there was no strong evidence that it led to improved survival. During the re-examination, the CHMP consulted the scientific advisory group. The CHMP agreed with the expert group's conclusion that, although there was no strong evidence of patients living longer, the available data from the main study (MT103-203) indicated a good durable response to blinatumomab, with an overall complete response rate for the primary endpoint full analysis set (defined as all subjects with an Ig or T-cell receptor polymerase chain reaction MRD assay with the minimum required sensitivity of 1 x 10(-4) at central lab established at baseline [n = 113]) as 79.6% (90/113; 95% confidence interval, 71.0-86.6), with a median time to complete MRD response of 29.0 days (range, 5-71). Therefore, the CHMP concluded that the benefits of blinatumomab outweigh its risks and recommended granting the change to the marketing authorization.The Committee for Orphan Medicinal Products, following reassessment, considered that significant benefit continued to be met and recommended maintaining the orphan designation and thus 10 years market exclusivity (the Orphan Designation is a legal procedure that allows for the designation of a medicinal substance with therapeutic potential for a rare disease, before its first administration in humans or during its clinical development). The marketing authorization holder for this medicinal product is Amgen Europe B.V.Implications for Practice Immunotherapy with blinatumomab has excellent and sustainable results, offering new hope for patients with minimal residual disease-positive acute lymphoblastic leukemia, a disease with poor prognosis. New recommendations and change of practice for treatment of this patient group are detailed.