Jazz Pharmaceuticals, Inc., Palo Alto, California.
Pediatr Blood Cancer. 2014 Jul;61(7):1232-8. doi: 10.1002/pbc.24938. Epub 2014 Jan 16.
L-Asparaginase is an integral component of standard chemotherapy regimens for the treatment of acute lymphoblastic leukemia (ALL). Clinical hypersensitivity, a common reason for treatment discontinuation, has been reported in 10-30% of patients receiving Escherichia coli-derived asparaginase. After hypersensitivity, E. coli-derived asparaginase should be discontinued and an alternative asparaginase preparation, such as asparaginase Erwinia chrysanthemi, may be initiated. We conducted a compassionate-use study to collect additional safety information on asparaginase Erwinia chrysanthemi and to support FDA approval of the product.
Patients with ALL or lymphoblastic lymphoma (LBL; N = 1368) who developed a hypersensitivity reaction (grade ≥2) to an E. coli-derived asparaginase participated in this trial. The recommended asparaginase Erwinia chrysanthemi dose was 25,000 IU/m(2) three days per week (Monday/Wednesday/Friday) for two consecutive weeks for each missed pegylated E. coli-derived asparaginase dose and 25,000 IU/m(2) for each missed nonpegylated asparaginase dose for the completion of their planned asparaginase treatment.
Adverse event reports and/or case report forms were completed for 940 patients. The most common adverse event (AE) was hypersensitivity (13.6%). Eighteen patients (1.9%) died during the study. Most patients (77.6%) completed their planned asparaginase treatment with asparaginase Erwinia chrysanthemi. There was no apparent difference in the incidence of the most commonly reported AEs with asparaginase treatment by age, administration, or disease state.
This study further established the safety profile of asparaginase Erwinia chrysanthemi in patients with ALL or LBL who had a hypersensitivity reaction to an E. coli-derived asparaginase.
L-天冬酰胺酶是治疗急性淋巴细胞白血病（ALL）的标准化疗方案的重要组成部分。在接受大肠杆菌衍生的天冬酰胺酶治疗的患者中，有 10-30%报告了临床过敏反应，这是导致治疗中断的常见原因。过敏反应后，应停止使用大肠杆菌衍生的天冬酰胺酶，并启动另一种天冬酰胺酶制剂，如欧文氏菌天冬酰胺酶。我们进行了一项同情使用研究，以收集关于欧文氏菌天冬酰胺酶的额外安全性信息，并支持该产品获得 FDA 批准。
本试验纳入了 1368 例对大肠杆菌衍生的天冬酰胺酶发生过敏反应（≥2 级）的 ALL 或淋巴母细胞淋巴瘤（LBL）患者。推荐的欧文氏菌天冬酰胺酶剂量为 25,000 IU/m2，每周 3 天（周一/周三/周五），用于替代每错过一个已用的聚乙二醇化大肠杆菌衍生的天冬酰胺酶剂量，以及每错过一个未用的非聚乙二醇化天冬酰胺酶剂量，以完成其计划的天冬酰胺酶治疗。
完成了 940 例患者的不良事件报告和/或病例报告表。最常见的不良事件（AE）是过敏反应（13.6%）。18 例患者（1.9%）在研究期间死亡。大多数患者（77.6%）完成了他们计划的欧文氏菌天冬酰胺酶治疗。根据年龄、给药途径或疾病状态，天冬酰胺酶治疗时最常报告的 AE 的发生率没有明显差异。
本研究进一步确定了欧文氏菌天冬酰胺酶在对大肠杆菌衍生的天冬酰胺酶过敏反应的 ALL 或 LBL 患者中的安全性。
