BESPONSA(inotuzumab ozogamicin)是首个也是唯一一种CD22靶向抗体药物偶联物, 用于治疗成人复发或难治性前体B细胞急性淋巴细胞白血病.
2017年8月21日，美国FDA正式批准辉瑞旗下抗白血病新药inotuzumab ozogamicin(商标名 Besponsa 辉瑞开发药品)用于成人复发性及难治性前体B细胞淋巴细胞白血病（ALL）。
FDA卓越肿瘤中心（Oncology Center of Excellence）主任兼新药审评中心OHOP部门代理主任Richard Pazdur博士表示，对于那些对初治方案无反应或者复发的B细胞ALL成人患者而言，生存时间往往很短。此前，临床上鲜有有效的药物治疗，而Besponsa的获批，将为临床患者提供一种全新的治疗模式和靶点。
B细胞ALL表现为B淋巴细胞在骨髓中异常增殖，影响造血功能，疾病进展极快。据美国国家肿瘤协会预测，2017年全美预计有5970名患者确诊B细胞ALL，其中约1440面临死亡威胁。
FDA的审批意见主要依据Besponsa的一项疗效及安全性临床试验。该试验共招募326名经治疗的复发性或难治性B细胞ALL患者参与。这些患者被随机分成两组，分别接受Besponsa或者化疗，考察治疗后的患者完全缓解率（CR）。结果显示Besponsa治疗组完全缓解率达到35.8%，中位生存期为8.0个月。化疗组完全缓解率为17.4%，中位生存期为4.9个月。
Besponsa的不良反应主要表现为血小板降低、白细胞减少、中性粒细胞减少、感染、贫血、疲乏、出血、发热、呕吐、头痛、发热性嗜中性球减少症、肝损伤（转氨酶或γ-谷氨酰转移酶升高）、腹痛及高胆红素血症、Q-T间期延长等。FDA建议，孕妇和哺乳期女性慎用Besponsa，该药可能对胎儿或者新生儿生长发育存在不良影响。
FDA审批意见中，对Besponsa治疗加以黑框警示：对治疗过程中出现严重肝损伤（包括肝静脉闭塞性疾病和肝窦阻塞综合征）的患者，需立即中止治疗或者减量。若出现肝静脉闭塞性疾病（VOD），需立即停药，情况严重者需加予标准抗VOD治疗。此外，黑框警示提示，经干细胞移植后再接受Besponsa治疗的患者，死亡风险将有所提高。
Besponsa是一种抗体药物偶联物，靶向结合癌细胞表面CD22抗原，抑制其异常增殖。此前先后获得FDA授予的"孤儿药"资格、突破性疗法和优先审批权，最终为其冲刺上市缩短了大量的时间。
BESPONSA(inotuzumab ozogamicin)
CORVERT Rx
Generic Name and Formulations:
Ibutilide fumarate 0.1mg/mL; soln for IV infusion.
Company:
Pfizer Inc.
Select therapeutic use: CHF and arrhythmias
Indications for CORVERT:
Rapid conversion of atrial fibrillation or atrial flutter of recent onset to sinus rhythm.
Adult:
Give by IV infusion over 10 minutes. ≥18yrs: (≥60kg) initially 1mg; (<60kg) initially 0.01mg/kg. If no response, may repeat second 10-minute infusion of equal strength given 10 minutes after first infusion. Discontinue infusion as soon as the presenting arrhythmia has terminated, or if sustained/nonsustained ventricular tachycardia or marked QT prolongation occurs.
Children:
<18yrs: not recommended.
Warnings/Precautions:
Risk of fatal arrhythmias (eg, sustained polymorphic ventricular tachycardia, usually associated with QT prolongation (torsades de pointes), but sometimes without documented QT prolongation may occur. Be experienced with the treatment and monitoring of life-threatening arrhythmias before administering. Have cardiac monitoring equipment and proper medication available. Correct hypokalemia and hypomagnesemia before starting. Monitor ECG continuously for at least 4 hours post infusion or until QTC returned to baseline. Proarrhythmia conditions (eg, ventricular arrhythmias, atrial flutter or fibrillation, QTC intervals >440 msec, hypokalemia, history of CHF, low left ventricular ejection fraction). Previous polymorphic ventricular tachycardia: not recommended. Renal or hepatic dysfunction (monitor). Pregnancy (Cat.C). Nursing mothers: not recommended.
Interactions:
Class Ia antiarrhythmics (eg, disopyramide, quinidine, procainamide) or other Class III drugs (eg, amiodarone, sotalol): do not give concomitantly or within 4 hours post-infusion. QT prolongation with phenothiazines, tricyclic and tetracyclic antidepressants, H1 receptor antagonists. Caution with digoxin.
Pharmacological Class:
Class III antiarrhythmic.
Adverse Reactions:
Ventricular extrasystoles, sustained or nonsustained polymorphic ventricular tachycardia, sustained monomorphic ventricular tachycardia, headache, hypo- or hypertension, tachycardia, bundle branch block, AV block, nausea, QT segment prolonged, bradycardia.
How Supplied:
Single-dose vial (10mL)—1