2016年4月7日,由美国医药巨头强生（JNJ）开发的新型抗癌药Darzalex（daratumumab）近日在欧洲药品管理局（EMA）人用医药产品委员会（CHMP）支持有条件批准Darzalex用于既往已接受治疗（包括一种蛋白酶抑制剂PI和免疫调节剂IMiD）且治疗后病情恶化的复发性或难治性多发性骨髓瘤（MM）成人患者。此前，Darzalex已于2015年11月获美国FDA加速批准，该药是FDA批准治疗多发性骨髓瘤（MM）的首个单克隆抗体药物。
CHMP的积极意见，是基于2项开放式临床研究的数据。第一项研究中，106例患者接受Darzalex治疗，其中29%的患者经历了肿瘤完全或部分缩小，这种缩小平均持续了7.4个月。第二个研究中，42例患者接受Darzalex治疗，其中36%的患者经历肿瘤完全或部分缩小。
研究中，Darzalex治疗最常见的副作用为输注相关反应、疲劳、发热、咳嗽、恶心、背痛、上呼吸道感染、贫血、粒细胞减少及血小板减少。
daratumumab是一种人源化抗CD38单克隆抗体，具有广谱杀伤活性，靶向结合多发性骨髓瘤细胞表面高度表达的跨膜胞外酶CD38分子，可通过多种机制诱导肿瘤细胞的快速死亡。目前，daratumumab正处于5个临床III期研究。除了多发性骨髓瘤，daratumumab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）。
关于多发性骨髓瘤：
多发性骨髓瘤（multiple myeloma，MM）是一种浆细胞癌，见于骨髓。多发性骨髓瘤中，一组浆细胞（或骨髓瘤细胞）转化为癌细胞并增生，使浆细胞的数目高于正常水平。由于浆细胞在体内广泛游走，有可能累及体内多数骨骼，可能导致压缩性骨折、骨溶解性病灶和相关疼痛。多发性骨髓瘤可导致若干严重健康问题，累及骨骼、免疫系统、肾脏和个体的红细胞计数，部分较常见症状包括骨骼疼痛和疲乏，疲乏是贫血的症状。多发性骨髓瘤属罕见癌症，每年新发病例在美国约为20，000人、全球约为114，000人。
Darzalex is available in 100mg/5ml and 400mg/20ml doses meant for intravenous administration.
About DARZALEX™ (daratumumab) 
DARZALEX™ (daratumumab) injection for intravenous use is the first human CD38-directed monoclonal antibody (mAb) approved anywhere in the world.12 CD38 is a surface protein that is overexpressed on multiple myeloma cells.13 Daratumumab is believed to induce tumor cell death through apoptosis, in which a series of molecular steps in a cell lead to its death12,14 and multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).12,15,16 Five Phase 3 clinical studies with daratumumab in relapsed and frontline settings are currently ongoing. Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma and non-Hodgkin's lymphoma.
DARZALEX was approved on November 16, 2015 in the U.S. for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. DARZALEX is the first mAb to receive regulatory approval to treat relapsed or refractory multiple myeloma.12
In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize DARZALEX.17 Janssen is currently the global sponsor of all but one clinical study. DARZALEX is commercialized in the U.S. by Janssen Biotech, Inc.
DARZALEX™ (daratumumab) Important Safety Information – Professional
CONTRAINDICATIONS - None
WARNINGS AND PRECAUTIONS
Infusion Reactions - DARZALEX can cause severe infusion reactions. Approximately half of all patients experienced a reaction, most during the first infusion. Infusion reactions can also occur with subsequent infusions. Nearly all reactions occurred during infusion or within 4 hours of completing an infusion. Prior to the introduction of post-infusion medication in clinical trials, infusion reactions occurred up to 48 hours after infusion. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, and hypertension. Signs and symptoms may include respiratory symptoms, such as cough, wheezing, larynx and throat tightness and irritation, laryngeal edema, pulmonary edema, nasal congestion, and allergic rhinitis. Less common symptoms were hypotension, headache, rash, urticaria, pruritus, nausea, vomiting, and chills.
Pre-medicate patients with antihistamines, antipyretics and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt infusion for reactions of any severity and institute medical management as needed. Permanently discontinue therapy for life-threatening (Grade 4) reactions. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.
To reduce the risk of delayed infusion reactions, administer oral corticosteroids to all patients the first and second day after all infusions. Patients with a history of obstructive pulmonary disorders may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with obstructive pulmonary disorders.
Interference with Serological Testing - Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive Indirect Antiglobulin Test (Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient's serum. The determination of a patient's ABO and Rh blood type are not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX. Type and screen patients prior to starting DARZALEX.
Interference with Determination of Complete Response - Daratumumab is a human IgG kappa monoclonal antibody that can be detected on both, the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.
Adverse Reactions - The most frequently reported adverse reactions (incidence ≥20%) were: fatigue, nausea, back pain, pyrexia, cough, and upper respiratory tract infection.
Serious adverse reactions were reported in 51 (33%) patients. The most frequent serious adverse reactions were pneumonia (6%), general physical health deterioration (3%), and pyrexia (3%).