近日，美国食品和药物管理局（FDA）已批准CD38靶向抗体药物Sarclisa（isatuximab-irfc）联合泊马度胺和地塞米松（pom-dex），用于既往已接受过至少2种疗法（包括来那度胺和一种蛋白酶体抑制剂）的复发难治性多发性骨髓瘤（RRMM）成人患者。Sarclisa有望不久将在美国上市。
多发性骨髓瘤（MM）是第二常见的血液癌症，在美国影响了超过13万患者，每年约有3.2万美国人被诊断为多发性骨髓瘤。大多数患者最终不幸复发，对目前可用的疗法难治。Sarclisa联合泊马度胺和地塞米松（pom-dex）方案，将为这些患者提供一个重要的新治疗选择。
批准日期：2020年3月3日 公司：赛诺菲-安万特
SARCLISA（isatuximab-irfc）注射液，静脉使用
美国初次批准：2020年
作用机理
Isatuximab-irfc是IgG1衍生的单克隆抗体，可与造血和肿瘤细胞（包括多发性骨髓瘤细胞）表面表达的CD38结合。Isatuximab-irfcin诱导肿瘤细胞凋亡并激活免疫效应机制，包括抗体依赖性细胞介导的细胞毒性（ADCC），抗体依赖性细胞吞噬作用（ADCP）和补体依赖性细胞毒性（CDC）。Isatuximab-irfc抑制CD38的ADP-核糖基环化酶活性。Isatuximab-irfc可以在不存在CD38阳性靶肿瘤细胞的情况下激活自然杀伤（NK）细胞，并抑制CD38阳性T调节细胞。在单独的多发性骨髓瘤异种移植模型中，与单独的isatuximab-irfc相比，isatuximab-irfc和pomalidomide的组合增强了ADCC活性和直接肿瘤细胞杀伤力，与单独的isatuximab-irfc或pomalidomide的活性相比，增强了抗肿瘤活性。
适应症和用途
SARCLISA是针对CD38的溶细胞抗体，与波马利度和地塞米松联用，可用于治疗多发性骨髓瘤的成年患者，这些患者已接受至少两种先前的治疗方法，包括来那度胺和蛋白酶体抑制剂。
剂量和给药
•与地塞米松，对乙酰氨基酚，H2拮抗剂和苯海拉明一起使用。
•SARCLISA的推荐剂量为每周4周静脉输注10mg/kg，然后每2周与pomalidomide和地塞米松联合使用，直至疾病进展或出现无法接受的毒性。
•有关准备和管理的说明，请参阅“完整处方信息”。
剂量形式和强度
注射：
•单剂量小瓶中的100mg/5mL（20mg/mL）溶液
•单剂量小瓶中的500mg/25mL（20mg/mL）溶液
禁忌症
对isatuximab-irfc或其任何辅料严重过敏的患者。
警告和注意事项
•输液相关反应：中断SARCLISA并进行医疗处理。≥3级反应永久停止。
•中性粒细胞减少症：在治疗期间定期监测全血细胞计数。监测中性粒细胞减少症患者的感染迹象。
可能需要使用SARCLISA剂量延迟和使用集落刺激因子以改善中性粒细胞计数。
•第二原发恶性肿瘤（SPM）：根据IMWG指南监测患者第二原发恶性肿瘤的发展。
•实验室测试干扰：
o干扰血清学测试（间接抗球蛋白测试）：在开始治疗前对患者进行分类和筛查。告知血库患者已收到SARCLISA。
o干扰血清蛋白电泳和免疫固定
测试：SARCLISA可能会干扰用于监测M蛋白的检测方法，这可能会影响完全应答的确定。
•胚胎-胎儿毒性：可引起胎儿伤害。
不良反应
最常见的不良反应（≥20％的患者）是中性粒细胞减少，输注相关反应，肺炎，上呼吸道感染和腹泻。
血液学实验室最常见的异常（≥80％的患者）为贫血，中性粒细胞减少，淋巴细胞减少和血小板减少。
要报告可疑的不良反应，请与sanofi-aventisU.S。联系。LLC，请致电1-800-633-1610或FDA，请致电1-800-FDA-1088或www.fda.gov/medwatch。
在特定人群中的使用
哺乳期：建议不要母乳喂养。
包装供应/存储和处理方式
供应方式
SARCLISA（isatuximab-irfc）注射液为澄清至微乳白色，无色至微黄色溶液，基本不含可见颗粒，提供如下：
•纸箱中的一个100mg/5mL单剂量小瓶：NDC 0024-0654-01
•纸箱中的一个500mg/25mL单剂量小瓶：NDC 0024-0656-01
存储
将其存放在原始纸箱中36°F至46°F（2°C至8°C）的冰箱中，以避光。
不要冻结。不要摇晃。
处理与处置
丢弃溶液中未使用的部分。所有用于稀释和给药的材料均应按照标准程序进行处理。
完整说明资料附件：
http://products.sanofi.us/Sarclisa/sarclisa.pdf
FDA approves Sarclisa(isatuximab-irfc)for patients with relapsed refractory multiple myeloma
Sarclisa in combination with pomalidomide and dexamethasone(pom-dex)significantly reduced the risk of disease progression or death by 40% compared to pom-dex alone in a pivotal trial*FDA approval based on data from the only randomized Phase 3trial(ICARIA-MM)to eva luate an anti-CD38 in combination with pom-dex that has presented results to date*Multiple myeloma is the second most common blood cancer, affecting more than 130000 patients in the U.S.;approximately 32000 Americans are diagnosed with multiple myeloma each year
About Sarclisa
Sarclisa is a monoclonal antibody (mAb) that binds to the CD38 receptor on multiple myeloma cells.It is designed to induce programmed tumor cell death (apoptosis) and immunomodulatory activity.CD38 is highly and uniformly expressed on multiple myeloma cells and cell surface receptors, making it a potential target for antibody-based therapeutics such as Sarclisa.
Sarclisa has Orphan Drug Designation status from the FDA and the European Medicines Agency(EMA).In the second quarter of 2019, the EMA accepted for review the Marketing Authorization Application for use of Sarclisa in combination with pom-dex for the treatment of certain patients with RRMM. The safety and efficacy of Sarclisa has not been fully eva luated by any regulatory authority outside of the U.S.
Sarclisa continues to be eva luated in multiple ongoing Phase 3clinical trials in combination with current standard treatments for people with relapsed refractory or newly diagnosed multiple myeloma.It is also under investigation for the treatment of other blood cancer types(hematologic malignancies)and solid tumors.
IMPORTANT SAFETY INFORMATION AND INDICATION FOR U.S.PATIENTS
What is SARCLISA?
SARCLISA is a prescription medicine used in combination with pomalidomide and dexamethasone to treat adults who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor, to treat multiple myeloma.
It is not known if SARCLISA is safe and effective in children.
Do not receive SARCLISA if you have a history of severe allergic reaction to isatuximab-irfc or any of the ingredients in SARCLISA(see the list of ingredients in full Prescribing Information).
Before receiving SARCLISA, tell your healthcare provider about all of your medical conditions, including if you:
are pregnant or plan to become pregnant. SARCLISA may harm your unborn baby. You should not receive SARCLISA during pregnancy. 
Females who are able to become pregnant should use an effective method of birth control during treatment and for 5months after your last dose of SARCLISA. Talk to your healthcare provider about birth control methods that you can use during this time.
Tell your healthcare provider right away if you think you are pregnant or become pregnant during treatment with SARCLISA.
are breastfeeding or plan to breastfeed. It is not known if SARCLISA passes into your breast milk. You should not breastfeed during treatment with SARCLISA.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.