近日，美国食品和药物管理局(FDA)批准的ELZONRIS(tagraxofusp-erzs;SL-401)用于治疗2岁及以上成人和儿童(包括未接受治疗的人群和以前接受过治疗的人群)的blastic plasmacytoid树突状细胞瘤(BPDCN)。ELZONRIS是首个被批准用于BPDCN和cd123靶向治疗的药物。
批准日期：2018年12月21日 公司：Stemline Therapeutics, Inc.
ELZONRIS (tagraxofusp-erzs)注射,供注射使用
美国初步批准:2018年
警告:
毛细血管渗漏综合征请参阅完整的处方信息的完整框警告。
毛细管泄漏综合征(CLS)，可能是生命威胁或致命的，如果管理不当，可以发生在病人接受ELZONRIS等等。
作用机制
Tagraxofusp-erzs是由重组人白细胞介素-3 (IL-3)和截断白喉毒素(DT)融合蛋白组成的cd123定向细胞毒素，可抑制蛋白合成并导致cd123表达细胞的死亡。
适应症和用法
ELZONRIS是一种cd123靶向细胞毒素，用于治疗成人和2岁以上儿童blasticplasmacytoid树突状细胞瘤(BPDCN)。
剂量和管理
•在每次ELZONRISinfusion前使用h1-组胺拮抗剂、对乙酰氨基酚、皮质类固醇和h2 -组胺拮抗剂进行预处理。
•在21天周期的第1-5天，每天给药一次，每次12微克/公斤，持续15分钟。
•在住院环境中管理ELZONRIS的第一个周期。后续循环可在住院或适当的门诊环境中实施。
•补充重要的准备和管理信息是充分的处方信息。见完整的处方信息的指导，为准备和管理。
剂型和强度
注射:单次注射，每毫升1000微克。
禁忌症
•没有。
警告和预防措施
•过敏:监测患者的体征/症状并进行适当治疗。
•肝毒性:监测ALT和AST，如果转氨酶升高到正常上限的5倍以上，中断ELZONRIS。
不良反应
最常见的不良反应(发生率≥30%)毛细管leaksyndrome、恶心、疲劳、外周水肿、发热和体重增加。
最常见的实验室异常decreasesin白蛋白(发生率≥50%),血小板、血红蛋白,钙,钠,并增加inglucose、ALT和AST。如需报告疑似不良反应，请致电StemlineTherapeutics, Inc.(电话877-332-7961)或FDA(电话1- 800-fdaa-1088或www.fda.gov/medwatch)。
在特定人群中使用
哺乳期:建议女性不要母乳喂养
包装提供/存储和处理
提供
ELZONRIS (tagraxofusp-erzs)注射液是一种无防腐剂、无菌、透明、无色、1mLsolution中1000mcg的注射液，装在单剂量玻璃瓶中。每个纸盒包含一个小瓶(NDC 72187-0401-1)。
储存和处理
储存在冰箱在-25°C和-15°C (-13°F和5°F)。保护ELZONRIS从光存储在原来的包装，直到使用的时间。在室温下解冻瓶15°C和25°C之间(59°F (77°F)在准备之前[参见管理准备(2.3)]。小瓶解冻后不要再冷冻。容器过期后请勿使用。

FDA Approves ELZONRIS(tagraxofusp), the First Treatment for Blastic Plasmacytoid Dendritic Cell Neoplasm and First CD123-Targeted Therapy
U.S. Food and Drug Administration (FDA) has granted approval of ELZONRIS™ (tagraxofusp-erzs; SL-401) for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adult and pediatric patients two years and older, in both treatment-naïve and previously-treated populations. ELZONRIS is the first treatment approved for BPDCN and the first approved CD123-targeted therapy.
ELZONRIS Clinical Trial Design
The ELZONRIS BPDCN clinical trial was the largest prospective trial ever conducted in this disease. This multicenter, multi-cohort, open-label, single-arm, clinical trial (STML-401-0114; NCT 02113982) enrolled 47 patients with BPDCN, including 32 treatment-naïve and 15 previously-treated patients, at seven sites in the U.S. Patients received ELZONRIS intravenously on days 1-5 of a 21-day cycle for multiple consecutive cycles. The trial consisted of three stages: Stage 1 (lead-in, dose escalation), Stage 2 (expansion) and Stage 3 (pivotal, confirmatory). Patients were also enrolled in an additional cohort (Stage 4) to enable uninterrupted access to ELZONRIS.
ELZONRIS Efficacy and Safety
Approval was based on a multicenter, multicohort, open-label, single-arm clinical trial (STML-401-0114; NCT 02113982) in patients with treatment-naïve or previously-treated BPDCN. In the Stage 3 (pivotal) cohort, 13 patients with treatment-naïve BPDCN received ELZONRIS at the labeled dose and schedule. Efficacy was based on the rate of complete response or clinical complete response (CR/CRc), with CRc defined as complete response with residual skin abnormality not indicative of active disease. In this pivotal cohort, the CR/CRc rate was 53.8 percent (7/13) (95% CI: 25.1, 80.8). The median duration of CR/CRc was not reached (range: 3.9 to 12.2 months).
The safety of ELZONRIS was assessed in 94 adults with treatment-naïve or previously-treated myeloid malignancies treated with ELZONRIS at the labeled dose and schedule. The most common adverse reactions (incidence ≥30%) were capillary leak syndrome (CLS), nausea, fatigue, peripheral edema, pyrexia, and weight increase. The most common laboratory abnormalities (incidence ≥50%) were decreases in albumin, platelets, hemoglobin, calcium, sodium, and increases in glucose, alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
ELZONRIS Overall Clinical Program in BPDCN
Clinical data from Study STML-401-0114 (NCT 02113982) were presented at the American Society of Hematology (ASH) annual meeting earlier this month. In 29 treatment-naïve patients who received ELZONRIS at 12 mcg/kg/day, the overall response rate (ORR) was 90 percent (26/29) (95% CI: 72.6, 97.8). In these patients, the CR/CRc rate was 72 percent (21/29) (95% CI: 52.8, 87.3) with a median duration of CR/CRc not reached (range: 1.3 to 32.2 months). Forty-five percent (13/29) of these patients were bridged to stem cell transplant (SCT), following remission on ELZONRIS.
The median overall survival (OS), among 29 treatment-naïve patients who received ELZONRIS at 12 mcg/kg/day was not reached (range: 0.2 to 42.0 months, with median follow-up of 23.0 months [range: 0.2 to 41+ months]).
INDICATION
ELZONRIS is a CD123-directed cytotoxin for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients 2 years and older.
The ELZONRIS label contains a boxed warning for CLS, which may be life-threatening or fatal and can occur in patients receiving ELZONRIS. Physicians are advised to monitor for signs and symptoms of CLS and take actions as recommended in the full prescribing information.
WARNINGS AND PRECAUTIONS
Capillary Leak Syndrome
ELZONRIS can cause capillary leak syndrome (CLS), which may be life-threatening or fatal if not properly managed. The overall incidence of CLS in clinical trials was 55% in patients receiving ELZONRIS, including 46% in Grades 1 or 2, 6% in Grade 3, 1% in Grade 4, and 2 fatal events. Common signs and symptoms (incidence ≥20%) associated with CLS that were reported during treatment with ELZONRIS include hypoalbuminemia, edema, weight gain, and hypotension.
Capillary leak syndrome is defined as any event reported as CLS during treatment with ELZONRIS or the occurrence of at least 2 of the following CLS manifestations within 7 days of each other: hypoalbuminemia (including albumin value less than 3.0 g/dL), edema (including weight increase of 5 kg or more), hypotension (including systolic blood pressure <90 mmHg).
Before initiating therapy with ELZONRIS, ensure that the patient has adequate cardiac function and serum albumin is ≥3.2 g/dL.
During treatment with ELZONRIS, ensure that serum albumin levels are ≥3.5 g/dL and have not been reduced by ≥0.5 g/dL from the albumin value measured prior to dosing initiation of the current cycle. Monitor serum albumin levels prior to the initiation of each dose or more often as indicated clinically thereafter. Additionally, assess patients for other signs or symptoms of CLS, including weight gain, new onset or worsening edema including pulmonary edema, hypotension, or hemodynamic instability.
Counsel patients to seek immediate medical attention should signs or symptoms of CLS occur at any time.
https://www.stemlinearc.com/resources/ELZONRIS_US_Full_Prescribing_Information.pdf