Department of Pharmacy, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Medicine, Icahn School of Medicine/Mount Sinai St. Luke's-West Hospital, New York, NY, USA.
Leuk Lymphoma. 2021 Jan;62(1):176-184. doi: 10.1080/10428194.2020.1824068. Epub 2020 Sep 26.
Pegaspargase is a modified version of asparaginase with prolonged asparagine depletion. It appears to be safe in adults <40 years old, but has a unique spectrum of toxicities, the risks of which appear to increase with age. The primary objective of this study was to evaluate pegaspargase tolerability and toxicity as assessed by evaluation of incidence and severity of adverse events. Secondary objectives included characterization of the reasons underlying pegaspargase discontinuation, when applicable. Grade 3/4 asparaginase-related toxicities with ≥10% incidence included: hyperbilirubinemia, hyperglycemia, hypertriglyceridemia, hypoalbuminemia, hypofibrinogenemia, and transaminitis. 63% of patients (38 of 60) received all intended doses of pegaspargase, with the most common reasons for discontinuation noted as hypersensitivity (12%), hyperbilirubinemia/transaminitis (8%), and hematopoietic transplantation in complete remission (10%). This study suggests that while hepatotoxicity and other known adverse effects are common, with careful monitoring, pegaspargase can safely be administered to adults with ALL age ≥40 years old.
培门冬酶是一种经过改良的天冬酰胺酶,可延长天冬酰胺的消耗。它在 <40 岁的成年人中似乎是安全的,但具有独特的毒性谱,其风险似乎随着年龄的增长而增加。本研究的主要目的是通过评估不良反应的发生率和严重程度来评估培门冬酶的耐受性和毒性。次要目标包括在适用的情况下,确定导致培门冬酶停药的原因。发生率≥10%的 3/4 级与天冬酰胺酶相关的毒性包括:高胆红素血症、高血糖症、高三酰甘油血症、低白蛋白血症、低纤维蛋白原血症和转氨血症。63%的患者(60 例中的 38 例)接受了所有计划剂量的培门冬酶,最常见的停药原因是过敏反应(12%)、高胆红素血症/转氨血症(8%)和完全缓解的造血移植(10%)。本研究表明,虽然肝毒性和其他已知的不良反应很常见,但通过仔细监测,培门冬酶可以安全地用于年龄≥40 岁的 ALL 成年患者。