2011年3月25日，美国FDA于2011年3月25日批准ipilimumab（商标名称为Yervoy）用于治疗晚期黑色素瘤。
黑色素瘤是最危险的一种皮肤癌，也是最主要的一种致死性皮肤病。据美国国立癌症研究院统计，2010年全美国总共诊断出68130例黑色素瘤新病例，全年有8700人死于该病。
据FDA相关主管官员介绍，晚期黑色素瘤具有毁灭性，治疗药物极少，而且无一能有效延长患者寿命。

Yervoy是FDA批准的第一种确实能延长患者寿命的治疗晚期黑色素瘤药物。
Yervoy是一种单克隆抗体，能有效阻滞一种叫做细胞毒性T细胞抗原-4（CTLA-4）的分子。CTLA-4会影响人体的免疫系统，削弱其杀死癌细胞的能力。Yervoy的作用机制可能是帮助人体免疫系统识别、瞄准并攻击黑色素瘤癌细胞。其给药方式是静脉注射。

Yervoy的安全性与有效性经过一项单一的国际性研究得到验证。该项研究有676名黑色素瘤患者参加，所有的受试对象都对常用治疗药物无反应，并且癌细胞已经扩散或者无法通过手术予以切除。

该研究的主要目的是确定患者的生存期限，即开始服药至患者死亡的时间。
受试患者被随机分成三组：
第一组服用Yervoy加一种叫做gp100的试验性癌症疫苗；
第二组单独服用Yervoy；
第三组单独服用gp100。
试验结果是：同时服用Yervoy和gp100的患者及单独服用Yervoy的患者平均可生存大约10个月，而且单独服用gp100的串者平均生存期限只有6.5个月。
Yervoy的常见副作用（主要因自身免疫反应而引致）包括：疲乏、腹泻、皮肤红疹、内分泌不足、肠道炎症（结肠炎）等。12.9%的受试患者会发生致命性的自身免疫反应。一旦发生严重副作用，则立即停止服用Yervoy并使用皮质类固醇进行治疗，但此措施并不是对所有病人有效。由于Yervoy具有上述非同寻常且极严重的副作用，FDA要求医护人员及患者都应对此严重风险有足够的认识。
Yervoy由位于纽约市的布迈施贵宝公司（Bristol-Myers Squibb）销售
适应证和用途
YERVOY是一种人类的细胞毒性T淋巴细胞抗原4(CTLA-4)-阻断抗体适用于治疗不可切除的或转移黑色素瘤。

批准日期：2011年3月25日；公司：百时美施贵宝Bristol-Myers Squibb

部分中文Yervoy处方资料（仅供参考）

剂量和给药方法
（1）YERVOY 3 mg/kg静脉历时90分钟给予每3周总共四剂。
（2）对严重不良反应永远终止。

剂型和规格
（1）50 mg/10 mL(5 mg/mL)
（2）200 mg/40 mL(5 mg/mL)

禁忌证
无。

警告和注意事项
免疫介导不良反应：对严重反应永远终止。对中度免疫介导不良反应不给药直至返回基线，改善至轻度严重性，或完全解决，和患者正在接受低于7.5 mg泼尼松[prednisone]或等同物每天。对严重，持久，或复发性免疫介导反应给予全身高剂量皮质激素。
（1）免疫介导肝炎：每次YERVOY给药前评价肝功能检验。
（2）免疫介导内分泌病变：每次给药前监查甲状腺功能试验和临床化学。每次随访时对内分泌病变体征和症状评价。需要时开始激素替代治疗。

不良反应
最常见不良反应(≥5%)是疲乏，腹泻，瘙痒，皮疹，和结肠炎。

特殊人群中使用
（1）妊娠：根据动物资料，YERVOY可能致胎儿危害。
（2）哺乳母亲：终止哺乳或终止YERVOY。

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原产地英文商品名:
YERVOY 5mg/ml 200mg/vial
原产地英文药品名:
IPILIMUMAB
中文参考商品译名:
YERVOY 5毫克/毫升 200毫克/瓶
中文参考药品译名:
伊匹单抗
生产厂家中文参考译名:
百时美施贵宝
生产厂家英文名:
BRISTOL MYERS SQUIBB

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原产地英文商品名:
YERVOY 5mg/ml 50mg/vial
原产地英文药品名:
IPILIMUMAB
中文参考商品译名:
YERVOY 5毫克/毫升 50毫克/瓶
中文参考药品译名:
伊匹单抗
生产厂家中文参考译名:
百时美施贵宝
生产厂家英文名:
BRISTOL MYERS SQUIBB

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Bristol-Myers Squibb announced that Yervoy (ipilimumab injection) has been approved for the treatment of late stage (metastatic) melanoma. This approval was based on data from a study conducted in 676 patients with melanoma who had stopped responding to other FDA-approved or commonly used treatments for melanoma, and had disease that had spread or could not be surgically removed. Patients received Yervoy plus an experimental tumor vaccine called gp100, Yervoy alone, or the vaccine alone. Patients who received the combination of Yervoy plus the vaccine or Yervoy alone lived an average of about 10 months, while those who received only the experimental vaccine lived an average of 6.5 months.

Yervoy is a monoclonal antibody that blocks a molecule known as cytotoxic T-lymphocyte antigen (CTLA-4). CTLA-4 may play a role in slowing down or turning off the body's immune system, affecting its ability to fight off cancerous cells. Yervoy may work by allowing the body's immune system to recognize, target, and attack cells in melanoma tumors.

Drug type

• A targeted T-cell antibody

• Recombinant, human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking monoclonal antibody

Indications

• Treatment of unresectable or metastatic melanoma

Mechanism of action

• CTLA-4 is a negative regulator of T-cell activation

• Ipilimumab binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86.

• Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation

• Proposed mechanism of action is indirect, possibly through T-cell-mediated antitumor immune responses

• IgG1 kappa immunoglobulin with an approximate molecular weight of 148 kd; produced in mammalian (Chinese hamster ovary) cell culture

Dosage and administration

• IV solution

— 50 mg/10 mL (5 mg/mL)

— 200 mg/40 mL (5 mg/mL)

• 3 mg/kg IV every 3 weeks for a total of four doses

— infuse over 90 minutes

• Geriatric dosing

— No overall differences in safety or efficacy were reported in elderly patients

• Pediatric dosing

— Safety and efficacy not established

Pregnancy and lactation

• Pregnancy Category: C

— Use only if potential benefit justifies potential risk to fetus

— Human IgG1 is known to cross placental barrier; ipilimumab is an IgG1.

— Potential for drug to be transmitted from mother to developing fetus

• Lactation

— Unknown whether distributed in breast milk

— Because of potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue ipilimumab, taking into account importance of therapy to the mother

Black box warnings

• Severe and fatal immune-mediated adverse reactions due to T-cell activation and proliferation may involve any organ system

• Most common severe immune-mediated adverse reactions: dermatitis (including toxic epidermal necrolysis), endocrinopathy, enterocolitis, hepatitis, and neuropathy

• Reactions typically manifest during treatment but may occur weeks to months after discontinuation

• If severe immune-mediated reactions occur, permanently discontinue ipilimumab and initiate systemic high-dose corticosteroid therapy

• Assess signs and symptoms of dermatitis, endocrinopathy, enterocolitis, neuropathy

— Evaluate clinical chemistries, including liver function

• Other immune-mediated adverse reactions (<1%): hemolytic anemia, iritis, meningitis, nephritis, pericarditis, pneumonitis, uveitis

Cautions

• Withhold dose for moderate immune-mediated adverse reactions until return to baseline, improvement to mild severity, or complete resolution, and patient is receiving <7.5 mg/d prednisone or equivalent

• Administer systemic high-dose corticosteroids for severe, persistent, or recurring immune-mediated reactions

• Evaluate liver function before each dose

• Monitor thyroid function and clinical chemistries prior to each dose

• Evaluate at each visit for signs and symptoms of endocrinopathy and institute hormone replacement therapy (HRT) as needed

• Binding antibodies against ipilimumab may develop

Adverse effects

• Most frequent: dermatitis (immune-mediated manifestations), diarrhea, fatigue, pruritus, rash

• Less frequent: colitis, endocrinopathies including adrenal insufficiency, immune-mediated enterocolitis, immune-mediated hepatitis, hypogonadism, hypothyroidism

• Rare: angiopathy, arthritis, autoimmune thyroiditis, conjunctivitis, erythema multiforme, meningitis, myocarditis, pancreatitis, pericarditis, polymyalgia rheumatica, psoriasis, temporal arteritis, vasculitis

— Nephrotic immune-mediated manifestations: nephritis

— Neurologic immune-mediated manifestations: Guillain-Barré syndrome, peripheral motor neuropathy

— Ocular immune-mediated manifestations: iritis, uveitis

— Pulmonary immune-mediated manifestations: pneumonitis

Drug interactions

• Ipilimumab is a human monoclonal antibody not metab­olized by cytochrome P450 enzymes or other drug-metabolizing enzymes; therefore, it is not expected to inhibit or induce CYPs or other drug-metabolizing enzymes.

— Caution should be used with immunosuppressants such as corticosteroids, tacrolimus, cyclosporine, etc.

— Use the Nursing Immune-mediated Adverse Reaction checklist from Bristol-Myers Squibb at www.yervoy.com/hcp/pdf/rems-nursing-checklist.pdf before administering this drug.

What to tell your patient

• You have been prescribed ipilimumab, which is a monoclonal antibody. It attaches to cancer cells so your body's immune system can fight them.

• Ipilimumab is given as an infusion through a vein (intravenously or IV).

• Your doctor has prescribed this medication because he or she has judged that the benefit is greater than the risk of side effects.

• Ipilimumab can cause serious side effects in many parts of your body that can lead to death. Call your health care provider immediately if you experience any of the following symptoms.

— Stomach and bowel: blood in the stool or dark, tarry, sticky stool; diarrhea (loose stools) or more bowel movements than usual; stomach or abdominal pain or tenderness

— Eyes: blurry vision, double vision, or other vision problems; eye pain or redness

— Skin: blisters and/or peeling, mouth sores, skin rash with or without itching

— General: bleeding or bruising more easily than normal; changes in behavior, such as less sex drive, being irritable, or forgetful; dark urine; dizziness or fainting; feeling tired; fever; headache; nausea or vomiting; numbness or tingling in hands or feet; weakness of legs, arms, or face; yellowing of your skin or the whites of your eyes

• Even seemingly mild symptoms can lead to severe conditions if not treated promptly and appropriately.

• You should not treat any of these symptoms with over-the-counter (OTC) medications, dietary supplements, or prescription medications until you discuss the symptoms with your health care provider and he or she approves the use of these products.

• Be sure to tell all health care providers that you are being treated with ipilimumab. ONA