Darzalex（daratumumab 达雷木单抗）注射剂是被FDA批准对治疗多发性骨髓瘤的第一个单克隆抗体 2015年11月16日，美国食品和药品监管局（FDA）授权加速批准Darzalex（daratumumab）治疗有多发性骨髓瘤患者曽接受至少三种以前治疗。Darzalex是被批准对治疗多发性骨髓瘤的第一个单克隆抗体。 多发性骨髓瘤是发现在骨髓中。发生在感染斗争浆细胞（一种白血细胞类型）血癌的一种形式。这些癌性细胞多发地，产生一种异常蛋白和将其他健康细胞推出骨髓。这种疾病可能导致变弱的免疫系统和致其他骨或肾问题。美国国立癌症研究所估计今年美国将有26,850多发性骨髓瘤新病例和11,240例相关死亡。 FDA的药物评价和研究中心中血液学和肿瘤室主任Richard Pazdur，M.D.说：“在癌症细胞表面上发现靶向蛋白已导致重要肿瘤治疗的进展，” “Darzalex提供对其他治疗已成为耐药的有多发性骨髓瘤患者另外治疗选择。” Darzalex注射，作为一种输注给予，是一种单克隆抗体通过帮助在免疫系统中某些细胞攻击癌细胞作用。 在两项开放研究证实Darzalex的安全性和疗效。在106例参加者接受Darzalex的一项研究，29%患者他们的肿瘤负荷经历一个完全或部分减少，它持续共平均7.4个月。第二项研究中42例参加者接受Darzalex，36%他们的肿瘤负荷有完全或部分减少。 Darzalex的最常见副作用是输注-相关反应，疲乏，恶心，背痛，发热和咳嗽。Darzalex还可能导致感染-斗争白血细胞的低计数（淋巴细胞减少，中性细胞减少，和白细胞减少）或红血细胞（贫血）和血血小板的低水平（血小板减少）。 血库应被告知患者是接受Darzalex因为药物可能干预血库对需要血液输注患者所做的某些测试（例如抗体筛选）。正在妊娠妇女和计划成为妊娠妇女不应使用Darzalex，治疗期间和治疗后宫至少三个月应使用有效避孕。 FDA根据初步临床证据提示如被批准Darzalex可能提供超过可得到治疗实质上改进，对这个申请授予突破性指定。Darzalex还接受优先审评和孤儿药物指定。优先审评状态是授予对药物申请，如被批准，在治疗一种严重情况在安全性和有效性将是显着改进。孤儿药物指定 提供鼓励例如税收抵免，用户费用减免和孤儿药物专营权资格以帮助和鼓励对罕见疾病药物的开发。 Darzalex是在监管局的加速批准程序下批准，这个程序允许批准一个药物治疗一种严重或危及生命疾病根据临床数据显示药物对一种替代。性终点合理地可能预测对患者临床获益。这个程序提供患者较早得到鼓舞人有前途新药同时公司进行验证性临床试验。 Darzalex由宾州Horsham的Janssen Biotech公司上市。 批准日期：2015年11月16日；公司：Janssen Biotech，Inc. 【适应症和用途】 Darzalex是一种靶向人CD38-单克隆抗体，适用为有多发性骨髓瘤的治疗患者曽接受至少三次以前现治疗包括一种蛋白体抑制剂(PI)和一种免疫调节剂或是对PI和一种免疫调节剂双重难治性患者。 【剂型和规格】 注射液： ⑴在单剂量小瓶中100 mg/5 mL溶液 ⑵在单剂量小瓶中400 mg/20 mL溶液 【剂量和给药方法】 用皮质激素，解热药和抗组织胺预先给药。 稀释和作为静脉输注给予。 推荐剂量是16 mg/kg体重。 Darzalex® (daratumumab) DARZALEX®(daratumumab) is a human CD38-directed monoclonal antibody indicated for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double refractory to a PI and an immunomodulatory agent. DARZALEX Rx Pharmacological Class: CD38-directed monoclonal antibody. Active Ingredient(s): Daratumumab 100mg/5mL, 400mg/20mL; per vial; soln for IV infusion after dilution; contains mannitol; preservative-free. Company Janssen Biotech, Inc Indication(s): Treatment of multiple myeloma in patients who have received ≥3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent. Pharmacology: Daratumumab is an immunoglobulin G1 kappa human monoclonal antibody that binds to CD38 and inhibits the growth of CD38 expressing tumor cells. It exerts its action by inducing apoptosis directly through Fc mediated cross linking and immune-mediated tumor cell lysis through complement dependent cytotoxicity, antibody dependent cell mediated cytotoxicity, and antibody dependent cellular phagocytosis. Clinical Trials: Study 1, was an open-label trial evaluating Darzalex monotherapy in 106 patients with relapsed or refractory multiple myeloma who had received ≥3 prior lines of therapy including a PI and an immunomodulatory agent or who were double-refractory to a PI and an immunomodulatory agent. The primary endpoint was overall response rate (ORR) as determined by the Independent Review Committee assessment using International Myeloma Working Group criteria. Study 2 was an open-label dose escalation trial evaluating Darzalex monotherapy in 42 patients with relapsed or refractory multiple myeloma who had received ≥2 different cytoreductive therapies. In both studies, Darzalex 16mg/kg was administered with pre- and post-infusion medications. Treatment was continued until unacceptable toxicity or disease progression. Efficacy results from Study 1 showed an ORR of 29.2% for Darzalex (95% CI: 20.8, 38.9), with a median time to response of 1 month (range: 0.9–5.6 months) and a median duration of response of 7.4 months (range: 1.2–13.1+ months). In Study 2, ORR was 36% (95% CI: 21.6, 52) for Darzalex, with a median time to response of 1 month (range: 0.5–3.2 months). The median duration of response was not estimable for Study 2 (range: 2.2–13.1+ months). For more clinical trial data, see full labeling. Legal Classification: Rx Adults: Premedicate with IV corticosteroid, oral antipyretic, oral or IV antihistamine 1 hour prior to every infusion; and give oral corticosteroid on the first and second day after all infusions. Give only as IV infusion. 16mg/kg weekly on Weeks 1–8, every 2 weeks on Weeks 9–24, then every 4 weeks on Week 25 onwards until disease progression. Infusion rates and modifications for infusion reactions: see full labeling. Prophylaxis for herpes zoster reactivation: initiate antiviral prophylaxis within 1 week of starting therapy and continue for 3 months after treatment. Children: Not established. Warnings/Precautions: Should be administered by a healthcare professional with immediate access to emergency equipment and appropriate medical support. Monitor for infusion reactions; interrupt treatment for infusion reactions of any severity. Permanently discontinue if life-threatening (Grade 4) infusion reactions occur; for Grade 1, 2, or 3 reactions, reduce the infusion rate when restarting the infusion. History of obstructive pulmonary disorders: may require additional post-infusion drugs; consider prescribing short- or long-acting bronchodilators and inhaled corticosteroids. Interference with cross-matching and RBC antibody screening; type/screen patients prior to initiating treatment. Moderate-to-severe hepatic impairment. Pregnancy. Females of reproductive potential should use effective contraception during treatment and for 3 months after. Nursing mothers. Interaction(s) Interferes with Indirect Antiglobulin (Coombs) Test, serum protein electrophoresis and immunofixation assays leading to false (+) results. Adverse Reaction(s) Infusion reactions, fatigue, nausea, back pain, pyrexia, cough, upper respiratory tract infection. How Supplied: Single-dose vial—1 LAST UPDATED: 1/15/2016 Darzalex（daratumumab）获CHMP批准扩大适应症 欧洲药品管理局（EMA）人用医药产品委员会（CHMP）推荐扩大抗癌药Darzalex（daratumumab）现有的适应症，用于多发性骨髓瘤（MM）的二线治疗，具体为：将Darzalex联合标准护理方案[lenalidomide（来那度胺，一种免疫调节剂）+地塞米松（dexamethasone）]或[硼替佐米（bortezomib，蛋白酶抑制剂）+地塞米松]，用于既往接受过至少一次治疗的多发性骨髓瘤（MM）成人患者。 在欧盟，Darzalex于2016年5月首次获批，作为一种单药疗法用于既往接受治疗（包括一种蛋白酶抑制剂PI和免疫调节剂IMiD）后病情恶化的复发性和难治性多发性骨髓瘤患者。 在美国方面，Darzalex于2015年11月首次获批，作为一种单药疗法用于多发性骨髓瘤的三、四线治疗；去年底，Darzalex的2种三联方案获FDA批准，用于多发性骨髓瘤（MM）的二线治疗。 此次CHMP支持批准Darzalex用于二线治疗，是基于2项III期临床研究的数据，这2项研究均在既往接受过至少一次治疗的多发性骨髓瘤患者中开展。来自POLLUX（MMY3003）研究的数据显示，与来那度胺+地塞米松二联疗法相比，Darzalex+来那度胺+地塞米松三联疗法使疾病进展或死亡风险显著降低63%（p＜0.0001）。来自CASTOR （MMY3004）研究的数据显示，与硼替佐米+地塞米松二联疗法相比，Darzalex+来那度胺+地塞米松三联疗法使疾病进展或死亡风险显著降低61%（p＜0.0001）。 Darzalex是全球获批的首个CD38介导性、溶细胞性抗体药物，具有广谱抗肿瘤活性，可靶向结合多发性骨髓瘤及多种实体瘤细胞表面高度表达的跨膜胞外酶CD38分子，通过多种免疫介导的作用机制诱导肿瘤细胞的快速死亡，包括互补依赖性细胞毒作用（CDC）、抗体依赖性细胞介导的细胞毒作用（ADCC）和抗体依赖性细胞吞噬作用（ADCP）以及通过细胞凋亡（apoptosis）。此外，Darzalex也已被证明能够靶向肿瘤微环境中的免疫抑制细胞从而表现出免疫调节活性。 Darzalex是杨森公司大力开发的一款产品，除了多发性骨髓瘤，Darzalex也有潜力治疗高表达CD38分子的其他类型肿瘤，包括弥漫性大B细胞淋巴癌（DLBCL）、慢性淋巴细胞白血病（CLL）、急性淋巴细胞白血病（ALL）、浆细胞性白血病（PCL）、急性髓性白血病（AML）、滤泡性淋巴瘤（FL）和套细胞淋巴瘤（MCL）等。