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更新于：2025-12-07
Methoxy Polyethylene Glycol-Epoetin Beta
甲氧聚二醇重组人促红素
更新于：2025-12-07
概要
基本信息
最高研发阶段批准上市 |
首次获批日期 欧盟 (2007-07-20), |
最高研发阶段(中国)批准上市 |
特殊审评- |
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结构/序列
Sequence Code 8988
来源: *****
关联
121
项与 甲氧聚二醇重组人促红素 相关的临床试验CTRI/2025/01/078921
A randomized, observer blind, parallel-group, active controlled, single dose study to compare pharmacokinetic, pharmacodynamic, safety and immunogenicity of Pegylated Erythropoietin 100 mcg/0.3 ml injection (PEG-EPO) of Incepta and Methoxy Polyethylene Glycol-Epoetin Beta 100 micrograms/0.3 ml solution for injection of Roche (Mircera) in healthy adult human subjects. - NIL
开始日期2025-01-21 |
申办/合作机构 |
TCTR20190718006
A RANDOMIZED, CONTROLLED, OPEN-LABEL, SINGLE-CENTER, PARALLEL GROUP STUDY TO ASSESS THE EFFECT OF MIRCERA ON DELAYING DIALYSIS IN ANEMIC PATIENTS WITH STAGE 5 CHRONIC KIDNEY DISEASE NOT ON DIALYSIS
开始日期2019-03-19 |
申办/合作机构- |
NCT03552393
An Open-Label, Single-Arm, Multicenter Study to Ascertain the Optimal Starting Dose of MIRCERA® Given Subcutaneously for the Maintenance Treatment of Anemia in Pediatric Patients With Chronic Kidney Disease on Dialysis or Not Yet on Dialysis.
Ascertain the starting dose of Mircera given subcutaneously for the maintenance treatment of anemia in pediatric participants with chronic kidney disease (CKD) on dialysis or not yet on dialysis when switching from stable subcutaneous (SC) maintenance treatment with epoetin alfa, epoetin beta, or darbepoetin alfa.
开始日期2018-08-03 |
申办/合作机构 |
100 项与 甲氧聚二醇重组人促红素 相关的临床结果
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100 项与 甲氧聚二醇重组人促红素 相关的转化医学
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100 项与 甲氧聚二醇重组人促红素 相关的专利（医药）
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474
项与 甲氧聚二醇重组人促红素 相关的文献（医药）2026-01-01·TALANTA
Selection, characterization and the application of the RNA aptamer in the capture assay of Erythropoietin (EPO)
Article
作者: Gopinath, Subash C B ; Citartan, Marimuthu ; Shuid, Ahmad Naqib ; Tang, Thean-Hock
Erythropoietin (EPO) is an erythropoietic growth factor that induces the production of red blood cells. However, this protein is also extensively manipulated by athletes to illegally enhance their performance, a phenomenon known as doping. Generating a feasible molecular recognition element against EPO would be beneficial for doping detection. In this study, we have successfully isolated an RNA aptamer against EPO using SELEX. Termed REPORA-6, this RNA aptamer has an estimated binding affinity of 25 ± 1 nM. REPORA-6 RNA aptamer also retains its binding against degylosylated EPO and interacts with both Epoetin Beta and Mircera, suggesting that this aptamer binds to the protein domain of the recombinant EPO despite the variation in the glycosylation side chains. Ethylnitrosourea mapping, in-line probing assay and docking revealed important nucleotides for interaction with EPO. Capitalizing these findings, a truncated RNA aptamer was derived, REPORA-6b RNA. This aptamer has an improved binding affinity of 22 ± 2 nM. We have incorporated this aptamer into a capture assay and found out that the limit of detection achieved was 19.6 pM. REPORA-6b RNA has an immense potential in applications involving doping detection of EPO.
2026-01-01·JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
Aptamer enrichment strategy for the detection of erythropoietin-receptor agonists in blood samples: A potential alternative to antibody-based assays
Article
作者: Somay Selbes, Yeşim
Optimal detection of Erythropoietin receptor agonists (ERAs) in anti-doping analyses relies heavily on efficient immunopurification (IP) strategies. While antibody-based IP is routinely applied, aptamers have emerged as promising alternatives. This proof-of-principle study investigated the applicability of an anti-EPO DNA aptamer for ERA enrichment in serum, followed by Sarkosyl-Polyacrylamide Gel Electrophoresis (SAR-PAGE) analysis. The aptamer-based method successfully captured recombinant ERA variants (rEPO, dEPO, EPO-Fc, CERA) with defined limits of detection (LOD) in serum: 10 mIU/mL for rEPO, 10 pg/mL for dEPO, and 25 pg/mL for EPO-Fc and CERA. In comparison, the antibody-based method achieved lower serum LODs of 5 mIU/mL for rEPO, 5 pg/mL for dEPO, and 12.5 pg/mL for EPO-Fc and CERA. Both methods demonstrated good selectivity, as no non-specific bands were detected in blank serum matrices. However, endogenous blood EPO (bEPO) was not enriched by the aptamer, likely reflecting glycosylation-related structural differences between endogenous and recombinant isoforms. These findings highlight that aptamers can provide highly specific recognition of recombinant ERAs without cross-reactivity to bEPO, which may simplify interpretation in doping control analyses. Nonetheless, further optimization-such as refining immobilization chemistries, incorporating differently glycosylated EPO forms during SELEX, and sequence improvements-is required to enhance capture of native isoforms. Overall, this study establishes a foundation for aptamer-based enrichment as a complementary alternative to antibody-based methods in anti-doping applications.
2025-12-31·RENAL FAILURE
Optimizing hemodialysis management using bioelectrical impedance analysis: emphasizing the significance of the phase angle
Review
作者: Kim, Hongtae ; Son, Hyung-Eun ; Jeon, Hae Eun ; Hwang, Jin Ho ; Shin, Jungho ; Kim, Su Hyun ; Kwon, Soie ; Cho, Semin ; Cho, Jeong Min
Patients undergoing hemodialysis (HD) often experience complications, such as severe malnutrition, muscle wasting, and fluid overload, which significantly affect survival rates and quality of life. Accurate assessment and management of nutritional status and fluid retention are essential for improving patient outcomes. Bioelectrical impedance analysis (BIA), a noninvasive and practical tool, is increasingly used to assess body composition and fluid distribution in patients undergoing HD. The phase angle (PhA), a BIA parameter, reflects cellular integrity and serves as a reliable indicator of nutritional status and clinical prognosis. This review discusses the clinical utility of BIA in assessing nutritional status, fluid retention, and body composition in patients undergoing maintenance HD, with a particular focus on the PhA. The role of the PhA in predicting survival, frailty, sarcopenia, and erythropoiesis-stimulating agent resistance was explored. The application of personalized dry weight management guided by BIA has been proposed to optimize the care of patients undergoing HD. Despite limitations, including inter-device variability, lack of standardized cutoff values, and limited evidence, BIA represents a promising tool that may enhance clinical outcomes if integrated into routine clinical practice.
44
项与 甲氧聚二醇重组人促红素 相关的新闻（医药）2025-12-07
·罗氏制药
根据国家医保局2025年12月7日的公告，罗氏制药中国三款创新药，伊赫莱®（伊那利塞片）、高罗华®（格菲妥单抗注射液）、罗可适®（奥瑞利珠单抗注射液）首次纳入新版国家医保目录。
⚫︎ 伊赫莱®（伊那利塞片），首个精准靶向PIK3CA突变乳腺癌的药物。
⚫︎ 高罗华®（格菲妥单抗注射液），首个针对复发/难治弥漫大B细胞淋巴瘤进行固定周期治疗的双抗类T细胞疗法。
⚫︎ 罗可适®（奥瑞利珠单抗注射液），填补原发进展型多发性硬化（PPMS）的空白。
另有七款创新药，罗视佳®（法瑞西单抗注射液）、赫赛汀®（曲妥珠单抗注射液（皮下注射））、安圣莎®（盐酸阿来替尼胶囊）、罗圣全®（恩曲替尼胶囊）、佳罗华®（奥妥珠单抗注射液）、安适平®（萨特利珠单抗注射液）、美信罗®（甲氧聚二醇重组人促红素注射液）新增适应症及成功续约。
中国首个、目前唯一精准靶向PIK3CA突变的乳腺癌（HR+/HER2-）药物，获中美两国突破性疗法认定，于今年3月按1类新药在中国获批，几乎与全球同步上市。此次成功纳入医保更是实现了当年获批、当年纳入医保的中国速度。伊赫莱®作为首个纳入医保的PI3Kα抑制剂及突变体降解剂，不仅惠及HR+分型患者，也将加速推动乳腺癌治疗从“一刀切”的广谱方案，转向“以患者为中心”的精准分子靶向治疗，开启乳腺癌精准诊疗新格局。
即用型T细胞疗法（TCE）、国内1类新药、且获得CDE突破性疗法认定，本品用于复发/难治弥漫大B细胞淋巴瘤（DLBCL），至多给药12个周期。此次纳入医保目录具有双重里程碑意义：一方面，实现了T细胞疗法在国家基本目录中“从0到1”的突破，填补了基本医保对于此类疗法的保障空白；另一方面，极大地提升了该创新疗法的临床可及性，为在复发/难治性DLBCL患者带来突破性的创新治疗选择。
全球首个且目前唯一获批可同时用于治疗成人原发进展型和复发型多发性硬化(RMS）的疾病修饰治疗药物，于2025年3月在中国获批。此次成功纳入国家医保目录，罗可适®将填补PPMS的保障空白，开启高效治疗时代，1年仅需用药2次，提高患者用药依从性，助力我国进一步提高罕见病用药保障水平。
此前罗氏已纳入国家医保目录的药品，也在本次医保目录调整中成功新增适应症和续约。
罗圣全®（恩曲替尼胶囊）成功续约并新增NTRK基因融合阳性的1月龄以上至12岁以下儿童实体瘤适应症。另外，全球首个获批的眼科双特异性抗体药物罗视佳®（法瑞西单抗注射液）成功新增了“继发于视网膜中央静脉阻塞（CRVO）或半侧视网膜静脉阻塞（HRVO）的黄斑水肿”的适应症，其突破创新的双通路机制可实现更快的积液消除和视力提升，为这部分眼底病患者带来创新的治疗方案，助力我国眼健康事业持续高质量发展。
同时，赫赛汀®（曲妥珠单抗注射液（皮下注射））、安圣莎®（盐酸阿来替尼胶囊）、佳罗华®（奥妥珠单抗注射液）、安适平®（萨特利珠单抗注射液）、美信罗®（甲氧聚二醇重组人促红素注射液）成功续约，继续造福广大HER2阳性乳腺癌、ALK阳性非小细胞肺癌、滤泡性淋巴瘤及视神经脊髓炎谱系疾病（NMOSD）及肾性贫血患者。
“在2025年国家医保目录调整周期内，罗氏3款创新药及适应症首次通过医保谈判顺利准入，另有多款创新药成功新增适应症和续约，将惠及更多中国患者。进入国家医保目录将进一步提升创新药品的可及性和可负担性，不仅彰显了中国政府提升中国老百姓健康福祉的决心，也体现了政府和企业携手持续提升人民群众用药保障水平所作出的共同努力。秉承‘先患者之需而行’的理念，罗氏将继续积极与政府部门、医疗机构和社会组织合作，让更多中国患者接受创新的个体化治疗方案，并助力‘健康中国2030’目标早日实现。”
2025-12-03
·知芽汇
“炎症”通常意味着红肿热痛——比如喉咙发炎、皮肤感染，但你是否想过，大脑也可能“发炎”，这种看不见摸不着的“神经炎症”，可能正是自闭症、多动症、抽动症，甚至某些孩子突然出现的强迫行为、情绪崩溃、恐惧进食背后的共同推手。
过去几十年，医学界普遍将这些行为问题归为“心理障碍”或“教养问题”，然而，近年来越来越多的研究揭示：免疫系统不仅守护身体免受病毒细菌侵袭，也深度参与了大脑的发育与功能调节。当免疫反应失调，尤其在生命早期关键窗口期（如孕期或婴幼儿阶段）出现免疫异常激活，就可能干扰神经回路的正常构建，埋下神经发育障碍的种子。
2025年8月，一项发表于国际权威期刊《国际分子科学杂志》的重要综述研究（Gagliano et al., 2025）系统梳理了神经发育障碍（NDDs）与儿童急性发作神经精神综合征（PANS）之间免疫-炎症联系。
这项由意大利、美国等多国科学家合作完成的研究，整合了来自全球上百项高质量研究，提出一个颠覆性观点：这些看似不同的精神行为问题，可能共享一条“免疫-神经炎症”的致病通路。
一、免神经发育障碍(NDDs)：真的是“心理问题”吗？
▸ 神经发育障碍(NDDs)
根据《精神障碍诊断与统计手册》（DSM-5），神经发育障碍 （NDDs）是一大类在儿童期起病、影响大脑发育和功能的疾病统称，主要包括：
· 自闭症谱系障碍(ASD):社交沟通困难、重复刻板行为、兴趣狭窄
· 注意缺陷多动障碍(ADHD):注意力难以集中、坐不住、冲动行事
· 抽动障碍/图雷特综合征(TD/TS):不自主地眨眼、耸肩、清嗓子，甚至发出怪声
· 智力障碍(ID):学习能力、生活自理能力显著低于同龄人
· 特定学习障碍(SLDs):阅读、书写或数学能力严重落后,智力通常正常
长期以来，这些障碍主要依靠行为观察和临床评估来诊断，缺乏明确的生物学标志物，因此，社会上常存在误解：认为这些问题源于“父母管教不当”“孩子懒惰”或“性格古怪”，许多家庭因此承受巨大压力，甚至陷入自责。
▸ 神经发育障碍(NDDs)生理共患病
现代神经科学证实，这些障碍源于大脑结构与功能的生物学差异，更关键的是，大量研究发现，神经发育障碍（NDDs）患者常常伴随其他身体问题：
· 过敏、湿疹、哮喘
· 自身免疫病（如1型糖尿病、桥本甲状腺炎、银屑病）
· 胃肠道问题（如便秘、腹泻、食物不耐受）
· 睡眠障碍、免疫力低下等
这种“共病现象”强烈提示：问题可能不止在大脑，而涉及全身性的生理失衡——尤其是免疫系统的异常，换句话说，孩子的“行为问题”，可能是身体内部“炎症风暴”的外在表现。
二、免疫系统：不只是“卫士”，更是大脑“建筑师”
要理解这一点，我们必须更新对免疫系统的认知，传统观念认为，大脑是一个“免疫豁免”器官——血脑屏障像一道坚固的城墙，将多数免疫细胞和炎症因子挡在外面，确保大脑环境稳定，但近二十年的研究不断完善并修正了这一看法：血脑屏障并非绝对“不可逾越”。
▸ 小胶质细胞：大脑的“常驻免疫工程师”
大脑中有一种特殊的免疫细胞，叫小胶质细胞，它们从胎儿期就开始工作，不仅是“哨兵”，更是“建筑师”：
1. 在发育早期,它们帮助神经元迁移到正确位置
2. 在儿童期，它们“修剪”多余的突触连接,让神经网络更高效
3. 它们还参与髓鞘形成（神经信号的“绝缘层”）,星形胶质细胞调控等关键过程
可以说，没有小胶质细胞的精准调控，就无法形成健康的大脑网络，但如果小胶质细胞被过度激活（如感染或毒素刺激），它们就会从“建设者”变成“破坏者”，释放大量炎症因子，损伤神经元，干扰突触可塑性。
▸ 免疫-脑对话：细胞因子是“信使”
免疫系统通过释放细胞因子（如IL-6、TNF-α、IL-17）等信号分子，与神经元“对话”，这些细胞因子：
1. 影响多巴胺、血清素等神经递质的合成与释放
2. 调节情绪、注意力、冲动控制
3. 改变神经回路的兴奋性与连接强度
因此，免疫系统不仅是防御者，更是大脑发育“合作者”甚至“指挥者”之一。
▸ 关键窗口期：生命最初1000天
从怀孕到孩子2岁，被称为“生命最初1000天”，这一时期，大脑以惊人速度发育，每天生成数百万神经元，建立万亿级连接，而免疫系统与大脑的互动尤为密切。
任何干扰（如母亲感染、压力、营养不良、环境污染）都可能通过免疫机制“编程”胎儿的大脑，使其在出生后对压力、感染等刺激更为敏感，更容易出现神经精神症状。
三、母体免疫激活：孩子大脑健康的“第一道警报”
综述中最引人注目的发现之一，是母亲在怀孕期间的免疫状态对孩子神经发育具有决定性影响。
▸ 什么是“母体免疫激活”（Maternal Immune Activation, MIA）？
当孕妇遭遇以下情况时，免疫系统会被激活，释放大量促炎细胞因子（如IL-6、TNF-α）：
· 感染（如流感、尿路感染、新冠）
· 自身免疫病（如系统性红斑狼疮、桥本甲状腺炎）
· 慢性炎症状态（如肥胖、哮喘、过敏）
这些炎症因子虽不能直接穿过胎盘，却可以：
· 改变胎盘功能，影响营养和氧气供应
· 激活胎儿自身的免疫系统
· 通过表观遗传机制（如DNA甲基化、microRNA调控）“标记”胎儿基因，使其在出生后长期处于高敏状态
▸ 科学证据有多强？
动物实验：
给怀孕小鼠注射模拟病毒的物质，其后代会出现社交退缩、重复行为、注意力缺陷——酷似人类ASD和ADHD。
人群研究：
1. 孕期母体IL-6水平升高，与孩子日后患自闭症、多动症、精神分裂症的风险显著相关
2. 母亲患有哮喘+极度肥胖，女婴患自闭症的风险可增加近17倍
3. 孕期C反应蛋白（CRP，炎症标志物）水平高，孩子10岁时被诊断为ADHD的几率上升40%
这些发现指向一个核心机制：母体的炎症信号“编程”了胎儿的免疫系统和大脑，为其一生埋下神经发育脆弱性的种子。
这解释了为何许多神经发育障碍(NDDs)患者具有家族聚集性——并非单纯遗传“精神病基因”，而是遗传了对免疫失调的易感性。
四、PANS——神经炎症“急先锋”：从慢性波动到急性爆发
如果说自闭症、多动症等是“慢性神经炎症”的表现，那么儿童急性神经精神综合征（PANS）则是其“急性暴发”形式。
▸ PANS是什么？家长如何识别？
PANS是一种突然发作（通常在数小时至数天内）的综合征，表现为：
·强迫症状：如反复洗手、检查门窗、害怕污染
·严重进食障碍：拒绝进食，担心食物有毒、噎住或“不干净”
·同时伴随至少两种以下症状：
1. 极度焦虑、情绪失控、易怒、攻击行为
2. 行为退化(如婴儿式说话、粘人、尿床)
3. 注意力涣散、记忆力下降、学业骤降
4. 运动协调障碍、字迹变差、感觉异常
5. 睡眠紊乱(失眠或嗜睡)、噩梦
6. 尿频、遗尿、瞳孔散大、心跳过快等自主神经症状
很多PANS患儿在发病前有感染史（如链球菌咽炎、流感、新冠），但并非所有病例都能找到明确病原体，因此，PANS的诊断不依赖特定感染，而强调“急性发作+多系统症状”。
▸ PANS与免疫有何关系？
研究发现，PANS患儿普遍存在：
·血清和脑脊液中炎症因子升高（如IL-17、TNF-α、IL-1β）
·针对基底神经节（大脑控制运动、习惯、情绪的区域）的自身抗体
·补体系统激活（免疫清除机制过度活跃，产生C4a等炎症介质）
·低水平自身免疫证据（如抗核抗体阳性、甲状腺抗体升高、乳糜泻筛查阳性）
·家族中自身免疫病高发（如多发性硬化、类风湿关节炎、红斑狼疮）
特别值得注意的是，约22%-71%的PANS患儿本身就有ADHD、ASD等神经发育障碍背景，这提示：PANS并非孤立疾病，而可能是已有神经发育脆弱性的孩子，在感染或应激触发下，免疫系统“过激反应”导致的症状急性恶化。
科学家提出“双重打击”模型：
第一次打击（孕期MIA或遗传易感）→ 大脑发育基础薄弱
第二次打击（儿童期感染/应激）→ 免疫系统失控，攻击神经回路 →PANS急性发作
五、跨越诊断界限：一个共享的“免疫—神经炎症”谱系
通常，医生按症状将孩子分门别类：自闭症、多动症、强迫症等等……但新研究证据表明，这些障碍在免疫机制上高度重叠，综述通过系统分析发现，各类障碍在以下六个维度上存在共性：
1. 遗传免疫相关改变
多个调控免疫反应与突触形成的基因（如SHANK3、NLRC4、SYNGAP1、PPM1D）在ASD、ADHD、PANS中均被发现存在变异，这些基因如同“双面开关”，既影响免疫细胞功能，又调控神经连接。
2. 家族自身免疫病史
几乎所有NDDs和PANS患者的家庭中，自身免疫病（如甲状腺炎、1型糖尿病、银屑病）的患病率都显著高于普通人群，PANS尤为突出——70%有家族史，20%的母亲患有严重自身免疫病。
3. 母体免疫激活（MIA）
孕期感染、炎症或自身抗体，是ASD、ADHD、精神分裂症的共同风险因素，虽然PANS尚无直接证据，但其相关基因在胎盘和脑血管中表达，暗示MIA可能奠定易感基础。
4. 炎症生物标志物
患者血清或脑脊液中普遍存在促炎因子（IL-6、TNF-α等）升高，且水平常与症状严重程度相关，PANS患者还表现出独特的代谢谱（如甘氨酸、谷氨酰胺异常），反映神经炎症与氧化应激。
5. 小胶质细胞失调
尸检和影像学研究证实，ASD、精神分裂症患者大脑中存在持续性小胶质细胞激活，动物模型显示，PANS相关的Th17/IL-17通路可直接激活小胶质细胞，破坏突触。
6. 血脑屏障功能障碍
虽然证据强弱不一，但ADHD、ASD、PANS均提示血脑屏障可能存在“漏洞”，使外周炎症因子或自身抗体得以进入中枢神经系统，引发“低级别神经炎症”。
因此，这些障碍不是彼此割裂的疾病，而是一个“免疫-神经炎症”谱系的不同表现，未来的精神疾病分类或许不再以症状为主，而转向基于生物学机制的“维度模型”——正如美国国立精神卫生研究所（NIMH）倡导的“研究领域标准”（RDoC）。
六、治疗新思路：从“压制症状”到“调节免疫”
目前，NDDs和PANS的主流治疗仍以行为干预和药物（如兴奋剂、抗精神病药）为主，但效果有限，且部分患者对药物反应不佳，甚至出现副作用，全球多项研究提示：对于存在免疫炎症证据的亚群，免疫调节可能成为关键突破口。
▸ 已有探索：
·抗生素/抗感染治疗：针对链球菌感染相关的PANDAS（PANS的一个亚型），青霉素等可预防复发
·静脉注射免疫球蛋白（IVIG）：通过调节抗体和免疫细胞，已在部分PANS和自闭症患儿中显示疗效，改善强迫、焦虑和认知功能
·皮质类固醇激素：如甲泼尼龙短期使用可快速抑制炎症，缓解急性症状
·血浆置换（Plasmapheresis）：清除循环中的致病性自身抗体，用于重症PANS
·靶向细胞因子药物：如抗IL-6（托珠单抗）、抗TNF-α（英夫利昔单抗）等生物制剂，正在临床试验中
然而，目前缺乏大规模随机对照试验（RCT）验证这些疗法的有效性与安全性，原因在于：
1.患者异质性高：并非所有ADHD或ASD都由免疫驱动
2.缺乏可靠生物标志物：难以精准识别“免疫亚型”
3.血脑屏障限制：许多药物难以进入中枢神经系统
▸ 未来方向：
·开发多模态生物标志物组合（如细胞因子+自身抗体+脑成像+代谢组学）
·根据免疫表型分层治疗（如“高炎症型” vs “免疫缺陷型”）
·在生命早期窗口期进行预防性干预（如优化孕期营养、控制母体炎症、调节肠道菌群）
七、给家长启示：关注“身体健康”，而不是仅仅“特殊教育”
如果你的孩子被诊断为神经发育障碍（NDDs），或出现突发性行为改变，请记住：
1. 这不是你的错，也不是孩子的“不听话”
背后可能有复杂的生物学机制，责备自己或强迫孩子“坚强一点”往往适得其反。
2. 全面体检很重要
建议排查：
·过敏原、食物不耐受
·自身免疫指标（如抗核抗体ANA、甲状腺抗体TPO-Ab）
·炎症标志物（C反应蛋白CRP、血沉ESR）
·维生素D、铁、锌等营养素水平
·肠道健康（如肠道菌群检测、乳糜泻筛查）
3. 记录症状与感染/应激事件的关系
如果每次感冒后抽动加重，或发烧后出现强迫行为，务必详细记录并告知医生，这可能是识别“免疫亚型”的关键线索。
4. 不要盲目尝试“消炎”
阿司匹林、布洛芬等非处方药对神经炎症作用有限，且可能有副作用，应在专业医生（如儿科神经免疫专家）指导下评估免疫干预的必要性。
5. 重视“生命最初1000天”
计划怀孕的女性建议如下：
·管理好慢性病（如哮喘、甲状腺疾病）
·保持健康体重，避免肥胖
·均衡饮食，补充叶酸、Omega-3
·减少压力，保证睡眠
·避免不必要的抗生素和环境毒素暴露
结语：“免疫神经精神病学”时代
长期以来，受身心二元论的影响，人们习惯于将“心理”与“生理”视为彼此分离的领域，然而，当代科学研究正不断打破这一传统界限，大脑并非孤立运作的器官，而是持续与免疫、代谢以及肠道微生态等系统进行复杂的动态的交互，共同构成一个高度整合的身心整体。
神经发育障碍（NNDs）和儿童急性神经精神综合征（PANS）的研究，不仅揭示了免疫炎症的核心作用，更呼吁我们要采用跨学科、多视角来看待儿童神经发育障碍，未来的诊疗，或将从“你是哪种病？”转向“你的免疫-神经网络发生了什么？”
正如该综述所言：“我们需要一场范式转变——承认大脑如同心脏、肝脏一样，也会因炎症而“生病”，并值得同样严谨的医学对待”。
这条路还很长——目前仍缺乏大规模的临床实验，免疫治疗也尚未成为标准方案，但每一步进展，都在为千万家庭带来新的希望！
参考文献：（向上滑动阅览）
向上滑动阅览
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2025-12-01
PRINCETON, N.J.--(BUSINESS WIRE)--Bristol Myers Squibb (NYSE: BMY) today announced the presentation of more than 95 data disclosures, including 27 oral presentations, across company-sponsored studies and external collaborations at the 67th American Society of Hematology (ASH) Annual Meeting, representing exciting advancements in the company’s next-generation hematology portfolio.
$BMY to present data across key research platforms in hematologic diseases at #ASH25.
Data from the company’s targeted protein degradation and cell therapy research platforms, as well as other hematology programs, will highlight development across key disease areas including multiple myeloma, lymphomas and myeloid diseases.
Key Presentations Include:
Golcadomide Delivers Durable Responses in Lymphoma Two-year follow-up confirms continued efficacy of first-in-class lymphoma CELMoD agent golcadomide + R-CHOP in previously untreated aggressive B-cell lymphoma, with high complete response rates (Oral presentation #476) Extended follow-up of golcadomide with or without rituximab shows promising activity in relapsed/refractory follicular lymphoma (FL) and diffuse-large B-cell lymphoma (DLBCL) (Oral presentations #1006 and #479)
Breyanzi ® Reinforces Long-Term Benefit in LBCL and FL Three-year Phase 2 TRANSCEND FL data show sustained safety and high efficacy of Breyanzi ® (lisocabtagene maraleucel) in third-line or later R/R FL, including high-risk subgroups (Oral presentation #467) Four-year follow-up from Phase 3 TRANSFORM confirms durable clinical benefit of Breyanzi in second-line R/R large B-cell lymphoma (LBCL) (Poster presentation #3710)
“Our goal is to deliver transformative medicines to help patients living with hematologic diseases and I am proud of the rich research we are showcasing at ASH this year,” said Cristian Massacesi, Executive Vice President, Chief Medical Officer and Head of Development, Bristol Myers Squibb. “Specifically, the data we will present from our targeted protein degradation research platform, with multiple drugs such as iberdomide, mezigdomide, golcadomide and BCL6 LDD, may redefine the treatment paradigm for many blood cancers. In addition, new liso-cel data support long-lasting benefit to patients, while novel cell therapy pipeline assets expand our effort across diseases.”
Select BMS studies presented at the 2025 ASH Annual Meeting:
Abstract Title
Author/
Presenter
Presentation
Type #
Session Date/Time (ET)
Mosunetuzumab (mosun) or glofitamab (glofit) in combination with golcadomide (Golca) demonstrated a manageable safety profile and encouraging efficacy in patients with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) (partner study)
Charalambos Andreadis
Oral Presentation #66
Saturday,
December 6,
2025: 09:30 AM - 11:00 AM ET
Safety and efficacy of elranatamab in combination with iberdomide in patients with relapsed or refractory multiple myeloma: Results from the phase 1b MagnetisMM-30 trial (partner study)
Attaya Suvannasankha
Oral Presentation #100
Saturday,
December 6,
2025: 10:15 AM - 10:30 AM ET
EMN26 trial (ISR): Phase II study of Iberdomide maintenance after autologous stem-cell transplantation in NDMM: Updated analyses
Niels W.C.J. van de Donk
Oral Presentation #101
Saturday, December 6, 10:30 AM - 10:45 AM ET
Impact of lenalidomide pre-apheresis on markers of T cell fitness and pharmacodynamic biomarkers in newly diagnosed multiple myeloma patients with suboptimal response to autologous stem cell transplantation
Debashree Basudhar
Oral Presentation #95
Saturday,
December 6,
2025: 10:30 AM - 10:45 AM ET
3-Year Follow-up of the S1826 Study Demonstrated Improved Progression-Free Survival with Nivolumab-AVD Compared to Brentuximab Vedotin-AVD in Advanced Stage Classic Hodgkin Lymphoma
Alex Herrera
Oral Presentation #151
Saturday December 6, 2025: 12:00 PM - 12:15 PM ET
ALLG MM25 (Viber-M; ISR): Phase Ib/II study of Venetoclax, Iberdomide and Dexamethasone in pts with t(11;14) RRMM: Interim analysis
Shirlene Sim
Oral Presentation #249
Saturday, December 6, 2:30 PM - 2:45 PM ET
Longitudinal analysis of MRD negativity and immune dynamics in patients with transplant-ineligible newly diagnosed multiple myeloma treated with iberdomide, daratumumab, and dexamethasone from the CC-220-MM-001 trial
Danny Jeyaraju
Poster Presentation #2255
Saturday, December 6, 2025: 5:30 PM - 7:30 PM ET
Assessment of pharmacodynamic efficacy biomarkers from a phase 1, first-in-human study of arlocabtagene autoleucel (arlo-cel) in relapsed and refractory multiple myeloma (RRMM)
Jesús Berdeja
Poster Presentation #2223
Saturday, December 6, 2025: 5:30 - 7:30 PM ET
Golcadomide (GOLCA), a potential, first-in-class, oral CELMoD agent, plus R-CHOP in patients (Pts) with previously untreated aggressive B-cell lymphoma (a-BCL): 24-month efficacy results
Grzegorz Nowakowski
Oral Presentation #476
Sunday,
December 7,
2025: 9:45 AM - 10:00 AM ET
Mezigdomide overcomes CRBN mutations emerging post IMiD Therapy
Edmond Watson
Oral Presentation #436
Sunday,
December 7,
2025: 10:15 AM - 10:30 AM ET
Golcadomide (GOLCA), a potential, first-in-class, oral CELMoD agent, ± rituximab (R) in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): Phase 1/2 study extended follow-up results
Marc Hoffmann
Oral Presentation #479
Sunday,
December 7,
2025: 10:30 AM - 10:45 AM ET
Three-year efficacy and longitudinal safety of lisocabtagene maraleucel (liso-cel) in patients with third-line or later (3L+) follicular lymphoma (FL) from TRANSCEND FL
Sairah Ahmed
Oral Presentation #467
Sunday,
December 7,
2025: 10:30 AM - 10:45 ET
BMS-986458, a potential first-in-class, bifunctional cereblon-dependent ligand-directed degrader of B-cell lymphoma 6 (BCL6) in patients with Relapsed/Refractory (R/R) non-Hodgkin lymphoma (NHL): Updated results from the phase 1 dose escalation study
Franck Morschhauser
Oral Presentation #480
Sunday,
December 7,
2025: 10:45 AM - 11:00 AM ET
Patient-reported outcomes (PROs) with lisocabtagene maraleucel (liso-cel) in patients with third line or later (3L+) R/R MZL from the phase 2 TRANSCEND FL study
Reem Karmali
Oral Presentation #709
Sunday,
December 7,
2025: 4:30 PM - 4:45 PM ET
Lisocabtagene maraleucel (liso-cel) versus standard of care (SOC) for second-line relapsed or refractory large b-cell lymphoma (LBCL): First results from long-term follow-up of TRANSFORM
Manali Kamdar
Poster Presentation #3710
Sunday,
December 7,
2025: 6:00 - 8:00 PM ET
Golcadomide (GOLCA), a potential, first-in-class, oral CELMoD agent, ± rituximab (R) in patients with relapsed/refractory follicular lymphoma (R/R FL): Phase 1/2 study extended follow-up results
Julio Chavez
Oral Presentation #1006
Monday,
December 8,
2025: 5:15 PM - 5:30 PM ET
Luspatercept initiated at the maximum-approved dose in transfusion-dependent lower-risk myelodysplastic syndromes: Interim analysis from MAXILUS
Amer Zeidan
Oral Presentation #789
Monday,
December 8,
2025: 11:00 - 11:15 AM ET
Clinical benefit of luspatercept in erythropoiesis-stimulating agent (ESA)-naive patients (pts) with early disease characteristics and very low-, low-, or intermediate-risk myelodysplastic syndromes (LR-MDS)-associated anemia: A post hoc analysis from the COMMANDS trial
Valeria Santini
Oral Presentation #792
Monday,
December 8,
2025: 11:45 - 12:00 PM ET
BMS-986458, a potential first-in-class, highly selective, and potent ligand-directed degrader (LDD) of B-cell lymphoma 6 (BCL6) combined with T-cell engagers (TCEs) demonstrates preclinical synergistic antitumor efficacy for the treatment of B-cell non-Hodgkin lymphoma (NHL)
Gauri Deb
Poster Presentation #5090
Monday, December 8, 2025: 6:00 PM - 8:00 PM ET
About Breyanzi
Breyanzi is a CD19-directed CAR T cell therapy with a 4-1BB costimulatory domain, which enhances the expansion and persistence of the CAR T cells. Breyanzi is made from a patient’s own T cells, which are collected and genetically reengineered to become CAR T cells that are then delivered via infusion as a one-time treatment. The treatment process includes blood collection, CAR T-cell creation, potential bridging therapy, lymphodepletion, administration, and side-effect monitoring.
Breyanzi is approved in the U.S. for the treatment of relapsed or refractory large B-cell lymphoma (LBCL) after at least one prior line of therapy, has received accelerated approval for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior lines of therapy and relapsed or refractory follicular lymphoma (FL) after two or more prior lines of systemic therapy, and is approved for the treatment of relapsed or refractory mantle cell lymphoma (MCL) after at least two prior lines of systemic therapy. Breyanzi is also approved in Japan, the European Union (EU), Switzerland, Israel, the United Kingdom, and Canada for the treatment of relapsed or refractory LBCL after at least one prior line of therapy; in Japan for the treatment of patients with relapsed or refractory high-risk FL after one prior line of systemic therapy, and in patients with relapsed or refractory FL after two or more lines of systemic therapy; in the EU, Switzerland and the UK for the treatment of relapsed or refractory FL after two or more lines of systemic therapy; and in the EU for relapsed or refractory MCL after at least two lines of systemic therapy including a Bruton’s tyrosine kinase (BTK) inhibitor.
Bristol Myers Squibb’s clinical development program for Breyanzi includes clinical studies in several types of lymphoma. For more information, visit clinicaltrials.gov.
Breyanzi U.S. FDA-Approved Indications
BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:
adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have: refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or relapsed or refractory disease after two or more lines of systemic therapy.
refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or
refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or
relapsed or refractory disease after two or more lines of systemic therapy.
Limitations of Use: BREYANZI is not indicated for the treatment of patients with primary central nervous system lymphoma.
adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
adult patients with relapsed or refractory follicular lymphoma (FL) who have received 2 or more prior lines of systemic therapy. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least 2 prior lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor.
Breyanzi U.S. Important Safety Information
WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, AND SECONDARY HEMATOLOGICAL MALIGNANCIES
Cytokine Release Syndrome
Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI. In clinical trials of BREYANZI, which enrolled a total of 702 patients with non-Hodgkin lymphoma (NHL), CRS occurred in 54% of patients, including ≥ Grade 3 CRS in 3.2% of patients. The median time to onset was 5 days (range: 1 to 63 days). CRS resolved in 98% of patients with a median duration of 5 days (range: 1 to 37 days). One patient had fatal CRS and 5 patients had ongoing CRS at the time of death. The most common manifestations of CRS (≥10%) were fever, hypotension, tachycardia, chills, hypoxia, and headache.
Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, diffuse alveolar damage, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).
Ensure that 2 doses of tocilizumab are available prior to infusion of BREYANZI.
Neurologic Toxicities
Neurologic toxicities that were fatal or life-threatening, including immune effector cell-associated neurotoxicity syndrome (ICANS), occurred following treatment with BREYANZI. Serious events including cerebral edema and seizures occurred with BREYANZI. Fatal and serious cases of leukoencephalopathy, some attributable to fludarabine, also occurred.
In clinical trials of BREYANZI, CAR T cell-associated neurologic toxicities occurred in 31% of patients, including ≥ Grade 3 cases in 10% of patients. The median time to onset of neurotoxicity was 8 days (range: 1 to 63 days). Neurologic toxicities resolved in 88% of patients with a median duration of 7 days (range: 1 to 119 days). Of patients developing neurotoxicity, 82% also developed CRS.
The most common neurologic toxicities (≥5%) included encephalopathy, tremor, aphasia, headache, dizziness, and delirium.
CRS and Neurologic Toxicities Monitoring
Monitor patients daily for at least 7 days following BREYANZI infusion for signs and symptoms of CRS and neurologic toxicities and assess for other causes of neurological symptoms. Continue to monitor patients for signs and symptoms of CRS and neurologic toxicities for at least 2 weeks after infusion and treat promptly. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated. Manage neurologic toxicity with supportive care and/or corticosteroid as needed. Advise patients to avoid driving for at least 2 weeks following infusion. Counsel patients to seek immediate medical attention should signs or symptoms of CRS or neurologic toxicity occur at any time.
Hypersensitivity Reactions
Allergic reactions may occur with the infusion of BREYANZI. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO).
Serious Infections
Severe infections, including life-threatening or fatal infections, have occurred in patients after BREYANZI infusion. In clinical trials of BREYANZI, infections of any grade occurred in 34% of patients, with Grade 3 or higher infections occurring in 12% of all patients. Grade 3 or higher infections with an unspecified pathogen occurred in 7%, bacterial infections in 3.7%, viral infections in 2%, and fungal infections in 0.7% of patients. One patient who received 4 prior lines of therapy developed a fatal case of John Cunningham (JC) virus progressive multifocal leukoencephalopathy 4 months after treatment with BREYANZI. One patient who received 3 prior lines of therapy developed a fatal case of cryptococcal meningoencephalitis 35 days after treatment with BREYANZI.
Febrile neutropenia developed after BREYANZI infusion in 8% of patients. Febrile neutropenia may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as medically indicated.
Monitor patients for signs and symptoms of infection before and after BREYANZI administration and treat appropriately. Administer prophylactic antimicrobials according to standard institutional guidelines. Avoid administration of BREYANZI in patients with clinically significant, active systemic infections.
Viral reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells. In clinical trials of BREYANZI, 35 of 38 patients with a prior history of HBV were treated with concurrent antiviral suppressive therapy. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing. In patients with prior history of HBV, consider concurrent antiviral suppressive therapy to prevent HBV reactivation per standard guidelines.
Prolonged Cytopenias
Patients may exhibit cytopenias not resolved for several weeks following lymphodepleting chemotherapy and BREYANZI infusion. In clinical trials of BREYANZI, Grade 3 or higher cytopenias persisted at Day 29 following BREYANZI infusion in 35% of patients, and included thrombocytopenia in 25%, neutropenia in 22%, and anemia in 6% of patients. Monitor complete blood counts prior to and after BREYANZI administration.
Hypogammaglobulinemia
B-cell aplasia and hypogammaglobulinemia can occur in patients receiving BREYANZI. In clinical trials of BREYANZI, hypogammaglobulinemia was reported as an adverse reaction in 10% of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion, was reported in 30% of patients. Monitor immunoglobulin levels after treatment with BREYANZI and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement as clinically indicated.
Live vaccines: The safety of immunization with live viral vaccines during or following BREYANZI treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during BREYANZI treatment, and until immune recovery following treatment with BREYANZI.
Secondary Malignancies
Patients treated with BREYANZI may develop secondary malignancies. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including BREYANZI. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes. Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Bristol Myers Squibb at 1-888-805-4555 for reporting and to obtain instructions on collection of patient samples for testing.
Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome (IEC-HS)
Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome (IEC-HS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI. Three of 89 (3%) safety evaluable patients with R/R CLL/SLL developed IEC-HS. Time to onset of IEC-HS ranged from 7 to 18 days. Two of the 3 patients developed IEC-HS in the setting of ongoing CRS and 1 in the setting of ongoing neurotoxicity. IEC-HS was fatal in 2 of 3 patients. One patient had fatal IEC-HS and one had ongoing IEC-HS at time of death. IEC-HS is a life-threatening condition with a high mortality rate if not recognized and treated early. Treatment of IEC-HS should be administered per current practice guidelines.
Adverse Reactions
The most common adverse reaction(s) (incidence ≥30%) in:
LBCL are fever, cytokine release syndrome, fatigue, musculoskeletal pain, and nausea. The most common Grade 3-4 laboratory abnormalities include lymphocyte count decrease, neutrophil count decrease, platelet count decrease, and hemoglobin decrease.
CLL/SLL are cytokine release syndrome, encephalopathy, fatigue, musculoskeletal pain, nausea, edema, and diarrhea. The most common Grade 3-4 laboratory abnormalities include neutrophil count decrease, white blood cell decrease, hemoglobin decrease, platelet count decrease, and lymphocyte count decrease.
FL is cytokine release syndrome. The most common Grade 3-4 laboratory abnormalities include lymphocyte count decrease, neutrophil count decrease, and white blood cell decrease.
MCL are cytokine release syndrome, fatigue, musculoskeletal pain, and encephalopathy. The most common Grade 3-4 laboratory abnormalities include neutrophil count decrease, white blood cell decrease, and platelet count decrease.
Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.
Reblozyl U.S. FDA-Approved Indications
REBLOZYL® (luspatercept-aamt) is indicated for the treatment of anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions.
REBLOZYL® (luspatercept-aamt) is indicated for the treatment of anemia without previous erythropoiesis stimulating agent use (ESA-naïve) in adult patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) who may require regular red blood cell (RBC) transfusions.
REBLOZYL® (luspatercept-aamt) is indicated for the treatment of anemia failing an erythropoiesis stimulating agent and requiring 2 or more red blood cell (RBC) units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).
REBLOZYL is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia.
Reblozyl U.S. Important Safety Information
WARNINGS AND PRECAUTIONS
Thrombosis/Thromboembolism
In adult patients with beta thalassemia, thromboembolic events (TEE) were reported in 8/223 (3.6%) of REBLOZYL-treated patients. TEEs included deep vein thrombosis, pulmonary embolus, portal vein thrombosis, and ischemic stroke. Patients with known risk factors for thromboembolism (splenectomy or concomitant use of hormone replacement therapy) may be at further increased risk of thromboembolic conditions. Consider thromboprophylaxis in patients at increased risk of TEE. Monitor patients for signs and symptoms of thromboembolic events and institute treatment promptly.
Hypertension
Hypertension was reported in 11.4% (63/554) of REBLOZYL-treated patients. Across clinical studies, the incidence of Grade 3 to 4 hypertension ranged from 2% to 9.6%. In patients with beta thalassemia with normal baseline blood pressure, 13 (6.2%) patients developed systolic blood pressure (SBP) ≥130 mm Hg and 33(16.6%) patients developed diastolic blood pressure (DBP) ≥80 mm Hg. In ESA-refractory or -intolerant adult patients with MDS with normal baseline blood pressure, 26 (30%) patients developed SBP ≥130 mm Hg and 23(16%) patients developed DBP ≥80 mm Hg. In ESA-naïve adult patients with MDS with normal baseline blood pressure, 23 (36%) patients developed SBP ≥140 mm Hg and 11 (6%) patients developed DBP ≥80 mm Hg. Monitor blood pressure prior to each administration. Manage new or exacerbations of preexisting hypertension using anti-hypertensive agents.
Extramedullary Hematopoietic (EMH) Masses
In adult patients with transfusion-dependent beta thalassemia, EMH masses were observed in 3.2% of REBLOZYL-treated patients, with spinal cord compression symptoms due to EMH masses occurring in 1.9% of patients (BELIEVE and REBLOZYL long-term follow-up study). In a study of adult patients with non-transfusion-dependent beta thalassemia, a higher incidence of EMH masses was observed in 6.3% of REBLOZYL-treated patients vs. 2% of placebo-treated patients in the double-blind phase of the study, with spinal cord compression due to EMH masses occurring in 1 patient with a prior history of EMH. REBLOZYL is not indicated for use in patients with non-transfusion-dependent beta thalassemia.
Possible risk factors for the development of EMH masses in patients with beta thalassemia include history of EMH masses, splenectomy, splenomegaly, hepatomegaly, or low baseline hemoglobin (<8.5 g/dL). Signs and symptoms may vary depending on the anatomical location. Monitor patients with beta thalassemia at initiation and during treatment for symptoms and signs or complications resulting from the EMH masses and treat according to clinical guidelines. Discontinue treatment with REBLOZYL in case of serious complications due to EMH masses. Avoid use of REBLOZYL in patients requiring treatment to control the growth of EMH masses.
Embryo-Fetal Toxicity
REBLOZYL may cause fetal harm when administered to a pregnant woman. REBLOZYL caused increased post-implantation loss, decreased litter size, and an increased incidence of skeletal variations in pregnant rat and rabbit studies. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 3 months after the final dose.
ADVERSE REACTIONS
Beta-Thalassemia
Serious adverse reactions occurred in 3.6% of patients on REBLOZYL. Serious adverse reactions occurring in1% of patients included cerebrovascular accident and deep vein thrombosis. A fatal adverse reaction occurred in 1 patient treated with REBLOZYL who died due to an unconfirmed case of acute myeloid leukemia (AML).
Most common adverse reactions (at least 10% for REBLOZYL and 1% more than placebo) were headache (26% vs 24%), bone pain (20% vs 8%), arthralgia (19% vs 12%), fatigue (14% vs 13%), cough (14% vs 11%), abdominal pain (14% vs 12%), diarrhea (12% vs 10%) and dizziness (11% vs 5%).
ESA-naïve adult patients with Myelodysplastic Syndromes
Grade ≥3 (≥2%) adverse reactions included hypertension and dyspnea.
The most common (≥10%) all-grade adverse reactions included diarrhea, fatigue, hypertension, peripheral edema, nausea, and dyspnea.
ESA-refractory or -intolerant adult patients with Myelodysplastic Syndromes
Grade ≥3 (≥2%) adverse reactions included fatigue, hypertension, syncope and musculoskeletal pain. A fatal adverse reaction occurred in 5 (2.1%) patients.
The most common (≥10%) adverse reactions included fatigue, musculoskeletal pain, dizziness, diarrhea, nausea, hypersensitivity reactions, hypertension, headache, upper respiratory tract infection, bronchitis, and urinary tract infection.
LACTATION
It is not known whether REBLOZYL is excreted into human milk or absorbed systemically after ingestion by a nursing infant. REBLOZYL was detected in milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because many drugs are excreted in human milk, and because of the unknown effects of REBLOZYL in infants, a decision should be made whether to discontinue nursing or to discontinue treatment. Because of the potential for serious adverse reactions in the breastfed child, breastfeeding is not recommended during treatment and for 3 months after the last dose.
DRUG ABUSE POTENTIAL
Abuse: Abuse of REBLOZYL may be seen in athletes for the effects on erythropoiesis. Misuse of drugs that increase erythropoiesis, such as REBLOZYL, by healthy persons may lead to polycythemia, which may be associated with life-threatening cardiovascular complications.
Please see U.S. Full Prescribing Information for REBLOZYL.
Opdivo U.S. Indications
OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.
OPDIVO® is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma.
OPDIVO® (nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC).
OPDIVO® (nivolumab) in combination with platinum-doublet chemotherapy, is indicated for neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements, followed by single-agent OPDIVO® as adjuvant treatment after surgery.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC).
OPDIVO® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
OPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.
OPDIVO® (nivolumab), in combination with cisplatin and gemcitabine, is indicated as first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC).
OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.
OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.
IMPORTANT SAFETY INFORMATION
Severe and Fatal Immune-Mediated Adverse Reactions
Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune-mediated adverse reactions.
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO or YERVOY. Early identification and management are essential to ensure safe use of OPDIVO and YERVOY. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and periodically during treatment with OPDIVO and before each dose of YERVOY. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO or YERVOY interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.
Immune-Mediated Pneumonitis
OPDIVO and YERVOY can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients receiving OPDIVO monotherapy, immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.9%), and Grade 2 (2.1%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 7% (31/456) of patients, including Grade 4 (0.2%), Grade 3 (2.0%), and Grade 2 (4.4%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 3.9% (26/666) of patients, including Grade 3 (1.4%) and Grade 2 (2.6%). In NSCLC patients receiving OPDIVO 3 mg/kg every 2 weeks with YERVOY 1 mg/kg every 6 weeks, immune- mediated pneumonitis occurred in 9% (50/576) of patients, including Grade 4 (0.5%), Grade 3 (3.5%), and Grade 2 (4.0%). Four patients (0.7%) died due to pneumonitis.
In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 6.0% (16/266) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 4.9% (13/266) of patients receiving OPDIVO, including Grade 3 (n=1) and Grade 2 (n=12).
Immune-Mediated Colitis
OPDIVO and YERVOY can cause immune-mediated colitis, which may be fatal. A common symptom included in the definition of colitis was diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients, including Grade 3 (1.7%) and Grade 2 (1%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated colitis occurred in 25% (115/456) of patients, including Grade 4 (0.4%), Grade 3 (14%) and Grade 2 (8%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated colitis occurred in 9% (60/666) of patients, including Grade 3 (4.4%) and Grade 2 (3.7%).
Immune-Mediated Hepatitis and Hepatotoxicity
OPDIVO and YERVOY can cause immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients, including Grade 4 (0.2%), Grade 3 (1.3%), and Grade 2 (0.4%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 15% (70/456) of patients, including Grade 4 (2.4%), Grade 3 (11%), and Grade 2 (1.8%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 7% (48/666) of patients, including Grade 4 (1.2%), Grade 3 (4.9%), and Grade 2 (0.4%).
OPDIVO in combination with cabozantinib can cause hepatic toxicity with higher frequencies of Grade 3 and 4 ALT and AST elevations compared to OPDIVO alone. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. In patients receiving OPDIVO and cabozantinib, Grades 3 and 4 increased ALT or AST were seen in 11% of patients.
Immune-Mediated Endocrinopathies
OPDIVO and YERVOY can cause primary or secondary adrenal insufficiency, immune-mediated hypophysitis, immune-mediated thyroid disorders, and Type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Withhold OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism; initiate hormone replacement as clinically indicated. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism; initiate hormone replacement or medical management as clinically indicated. Monitor patients for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated.
In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994), including Grade 3 (0.4%) and Grade 2 (0.6%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, adrenal insufficiency occurred in 8% (35/456), including Grade 4 (0.2%), Grade 3 (2.4%), and Grade 2 (4.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, adrenal insufficiency occurred in 7% (48/666) of patients, including Grade 4 (0.3%), Grade 3 (2.5%), and Grade 2 (4.1%). In patients receiving OPDIVO and cabozantinib, adrenal insufficiency occurred in 4.7% (15/320) of patients, including Grade 3 (2.2%) and Grade 2 (1.9%).
In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients, including Grade 3 (0.2%) and Grade 2 (0.3%).
In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypophysitis occurred in 9% (42/456), including Grade 3 (2.4%) and Grade 2 (6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypophysitis occurred in 4.4% (29/666) of patients, including Grade 4 (0.3%), Grade 3 (2.4%), and Grade 2 (0.9%).
In patients receiving OPDIVO monotherapy, thyroiditis occurred in 0.6% (12/1994) of patients, including Grade 2 (0.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, thyroiditis occurred in 2.7% (22/666) of patients, including Grade 3 (4.5%) and Grade 2 (2.2%).
In patients receiving OPDIVO monotherapy, hyperthyroidism occurred in 2.7% (54/1994) of patients, including Grade 3 (<0.1%) and Grade 2 (1.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hyperthyroidism occurred in 9% (42/456) of patients, including Grade 3 (0.9%) and Grade 2 (4.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hyperthyroidism occurred in 12% (80/666) of patients, including Grade 3 (0.6%) and Grade 2 (4.5%).
In patients receiving OPDIVO monotherapy, hypothyroidism occurred in 8% (163/1994) of patients, including Grade 3 (0.2%) and Grade 2 (4.8%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypothyroidism occurred in 20% (91/456) of patients, including Grade 3 (0.4%) and Grade 2 (11%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypothyroidism occurred in 18% (122/666) of patients, including Grade 3 (0.6%) and Grade 2 (11%).
In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients, including Grade 3 (0.4%) and Grade 2 (0.3%), and 2 cases of diabetic ketoacidosis. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, diabetes occurred in 2.7% (15/666) of patients, including Grade 4 (0.6%), Grade 3 (0.3%), and Grade 2 (0.9%).
Immune-Mediated Nephritis with Renal Dysfunction
OPDIVO and YERVOY can cause immune-mediated nephritis. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.5%), and Grade 2 (0.6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated nephritis with renal dysfunction occurred in 4.1% (27/666) of patients, including Grade 4 (0.6%), Grade 3 (1.1%), and Grade 2 (2.2%).
Immune-Mediated Dermatologic Adverse Reactions
OPDIVO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes.
YERVOY can cause immune-mediated rash or dermatitis, including bullous and exfoliative dermatitis, SJS, TEN, and DRESS. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes.
Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).
In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients, including Grade 3 (1.1%) and Grade 2 (2.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated rash occurred in 28% (127/456) of patients, including Grade 3 (4.8%) and Grade 2 (10%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated rash occurred in 16% (108/666) of patients, including Grade 3 (3.5%) and Grade 2 (4.2%).
Other Immune-Mediated Adverse Reactions
The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received OPDIVO monotherapy or OPDIVO in combination with YERVOY or were reported with the use of other PD-1/PD-L1 blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions: cardiac/vascular: myocarditis, pericarditis, vasculitis; nervous system: meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; ocular: uveitis, iritis, and other ocular inflammatory toxicities can occur; gastrointestinal: pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis; musculoskeletal and connective tissue: myositis/polymyositis, rhabdomyolysis, and associated sequelae including renal failure, arthritis, polymyalgia rheumatica; endocrine: hypoparathyroidism; other (hematologic/immune): hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis (HLH), systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection.
In addition to the immune-mediated adverse reactions listed above, across clinical trials of YERVOY monotherapy or in combination with OPDIVO, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in <1% of patients unless otherwise specified: nervous system: autoimmune neuropathy (2%), myasthenic syndrome/myasthenia gravis, motor dysfunction; cardiovascular: angiopathy, temporal arteritis; ocular: blepharitis, episcleritis, orbital myositis, scleritis; gastrointestinal: pancreatitis (1.3%); other (hematologic/immune): conjunctivitis, cytopenias (2.5%), eosinophilia (2.1%), erythema multiforme, hypersensitivity vasculitis, neurosensory hypoacusis, psoriasis.
Some ocular IMAR cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada–like syndrome, which has been observed in patients receiving OPDIVO and YERVOY, as this may require treatment with systemic corticosteroids to reduce the risk of permanent vision loss.
Infusion-Related Reactions
OPDIVO and YERVOY can cause severe infusion-related reactions. Discontinue OPDIVO and YERVOY in patients with severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Interrupt or slow the rate of infusion in patients with mild (Grade 1) or moderate (Grade 2) infusion-related reactions. In patients receiving OPDIVO monotherapy as a 60-minute infusion, infusion-related reactions occurred in 6.4% (127/1994) of patients. In a separate trial in which patients received OPDIVO monotherapy as a 60-minute infusion or a 30-minute infusion, infusion-related reactions occurred in 2.2% (8/368) and 2.7% (10/369) of patients, respectively. Additionally, 0.5% (2/368) and 1.4% (5/369) of patients, respectively, experienced adverse reactions within 48 hours of infusion that led to dose delay, permanent discontinuation or withholding of OPDIVO. In melanoma patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 2.5% (10/407) of patients. In HCC patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 8% (4/49) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, infusion-related reactions occurred in 5.1% (28/547) of patients. In MSI- H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, infusion-related reactions occurred in 4.2% (5/119) of patients. In MPM patients receiving OPDIVO 3 mg/kg every 2 weeks with YERVOY 1 mg/kg every 6 weeks, infusion-related reactions occurred in 12% (37/300) of patients.
Complications of Allogeneic Hematopoietic Stem Cell Transplantation
Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with OPDIVO or YERVOY. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between OPDIVO or YERVOY and allogeneic HSCT.
Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with OPDIVO and YERVOY prior to or after an allogeneic HSCT.
Embryo-Fetal Toxicity
Based on its mechanism of action and findings from animal studies, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. The effects of YERVOY are likely to be greater during the second and third trimesters of pregnancy. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with OPDIVO and YERVOY and for at least 5 months after the last dose.
Increased Mortality in Patients with Multiple Myeloma when OPDIVO is Added to a Thalidomide Analogue and Dexamethasone
In randomized clinical trials in patients with multiple myeloma, the addition of OPDIVO to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.
Lactation
There are no data on the presence of OPDIVO or YERVOY in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 5 months after the last dose.
Serious Adverse Reactions
In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. In Checkmate 066, serious adverse reactions occurred in 36% of patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of patients receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). In Checkmate 067, serious adverse reactions (74% and 44%), adverse reactions leading to permanent discontinuation (47% and 18%) or to dosing delays (58% and 36%), and Grade 3 or 4 adverse reactions (72% and 51%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.2%), colitis (10% and 1.9%), and pyrexia (10% and 1.0%). In Checkmate 238, serious adverse reactions occurred in 18% of patients receiving OPDIVO (n=452). Grade 3 or 4 adverse reactions occurred in 25% of OPDIVO-treated patients (n=452). The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of OPDIVO-treated patients were diarrhea and increased lipase and amylase. In Checkmate 816, serious adverse reactions occurred in 30% of patients (n=176) who were treated with OPDIVO in combination with platinum-doublet chemotherapy. Serious adverse reactions in >2% included pneumonia and vomiting. No fatal adverse reactions occurred in patients who received OPDIVO in combination with platinum-doublet chemotherapy. In Checkmate 77T, serious adverse reactions occurred in 21% of patients who received OPDIVO in combination with platinum-doublet chemotherapy as neoadjuvant treatment (n=228). The most frequent (≥2%) serious adverse reactions was pneumonia. Fatal adverse reactions occurred in 2.2% of patients, due to cerebrovascular accident, COVID-19 infection, hemoptysis, pneumonia, and pneumonitis (0.4% each). In the adjuvant phase of Checkmate 77T, 22% of patients experienced serious adverse reactions (n=142). The most frequent serious adverse reaction was pneumonitis/ILD (2.8%). One fatal adverse reaction due to COVID-19 occurred. In Checkmate 227, serious adverse reactions occurred in 58% of patients (n=576). The most frequent (≥2%) serious adverse reactions were pneumonia, diarrhea/colitis, pneumonitis, hepatitis, pulmonary embolism, adrenal insufficiency, and hypophysitis. Fatal adverse reactions occurred in 1.7% of patients; these included events of pneumonitis (4 patients), myocarditis, acute kidney injury, shock, hyperglycemia, multi-system organ failure, and renal failure. In Checkmate 9LA, serious adverse reactions occurred in 57% of patients (n=358). The most frequent (>2%) serious adverse reactions were pneumonia, diarrhea, febrile neutropenia, anemia, acute kidney injury, musculoskeletal pain, dyspnea, pneumonitis, and respiratory failure. Fatal adverse reactions occurred in 7 (2%) patients, and included hepatic toxicity, acute renal failure, sepsis, pneumonitis, diarrhea with hypokalemia, and massive hemoptysis in the setting of thrombocytopenia. In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 057, fatal adverse reactions occurred; these included events of infection (7 patients, including one case of Pneumocystis jirovecii pneumonia), pulmonary embolism (4 patients), and limbic encephalitis (1 patient). In Checkmate 743, serious adverse reactions occurred in 54% of patients receiving OPDIVO plus YERVOY. The most frequent serious adverse reactions reported in ≥2% of patients were pneumonia, pyrexia, diarrhea, pneumonitis, pleural effusion, dyspnea, acute kidney injury, infusion-related reaction, musculoskeletal pain, and pulmonary embolism. Fatal adverse reactions occurred in 4 (1.3%) patients and included pneumonitis, acute heart failure, sepsis, and encephalitis. In Checkmate 214, serious adverse reactions occurred in 59% of patients receiving OPDIVO plus YERVOY (n=547). The most frequent serious adverse reactions reported in ≥2% of patients were diarrhea, pyrexia, pneumonia, pneumonitis, hypophysitis, acute kidney injury, dyspnea, adrenal insufficiency, and colitis. In Checkmate 9ER, serious adverse reactions occurred in 48% of patients receiving OPDIVO and cabozantinib (n=320). The most frequent serious adverse reactions reported in ≥2% of patients were diarrhea, pneumonia, pneumonitis, pulmonary embolism, urinary tract infection, and hyponatremia. Fatal intestinal perforations occurred in 3 (0.9%) patients. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In Checkmate 205 and 039, adverse reactions leading to discontinuation occurred in 7% and dose delays due to adverse reactions occurred in 34% of patients (n=266). Serious adverse reactions occurred in 26% of patients. The most frequent serious adverse reactions reported in ≥1% of patients were pneumonia, infusion-related reaction, pyrexia, colitis or diarrhea, pleural effusion, pneumonitis, and rash. Eleven patients died from causes other than disease progression: 3 from adverse reactions within 30 days of the last OPDIVO dose, 2 from infection 8 to 9 months after completing OPDIVO, and 6 from complications of allogeneic HSCT. In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO (n=236). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis. In Checkmate 275, serious adverse reactions occurred in 54% of patients receiving OPDIVO (n=270). The most frequent serious adverse reactions reported in ≥2% of patients receiving OPDIVO were urinary tract infection, sepsis, diarrhea, small intestine obstruction, and general physical health deterioration. In Checkmate 274, serious adverse reactions occurred in 30% of patients receiving OPDIVO (n=351). The most frequent serious adverse reaction reported in ≥2% of patients receiving OPDIVO was urinary tract infection. Fatal adverse reactions occurred in 1% of patients; these included events of pneumonitis (0.6%). In Checkmate 901, serious adverse reactions occurred in 48% of patients receiving OPDIVO in combination with chemotherapy. The most frequent serious adverse reactions reporting in ≥2% of patients who received OPDIVO with chemotherapy were urinary tract infection (4.9%), acute kidney injury (4.3%), anemia (3%), pulmonary embolism (2.6%), sepsis (2.3%), and platelet count decreased (2.3%). Fatal adverse reactions occurred in 3.6% of patients who received OPDIVO in combination with chemotherapy; these included sepsis (1%). OPDIVO and/or chemotherapy were discontinued in 30% of patients and were delayed in 67% of patients for an adverse reaction. In Checkmate 8HW, serious adverse reactions occurred in 46% of patients receiving OPDIVO in combination with ipilimumab. The most frequent serious adverse reactions reported in ≥1% of patients who received OPDIVO with ipilimumab were adrenal insufficiency (2.8%), hypophysitis (2.8%), diarrhea (2.0%), abdominal pain (2.0%), small intestinal obstruction (2.0%), pneumonia (1.7%), acute kidney injury (1.4%), immune mediated enterocolitis (1.4%), pneumonitis (1.4%), colitis (1.1%), large intestinal obstruction (1.1%), and urinary tract infection (1.1%). Fatal adverse reactions occurred in 2 (0.6%) patients who received OPDIVO in combination with ipilimumab; these included myocarditis and pneumonitis (1 each). In Checkmate 8HW, serious adverse reactions occurred in 39% of patients receiving OPDIVO alone. The most frequent serious adverse reactions reported in >1% of patients who received OPDIVO as a single agent were intestinal obstruction (2.3%), acute kidney injury (1.7%), COVID-19 (1.7%), abdominal pain (1.4%), diarrhea (1.4%), ileus (1.4%), subileus (1.4%), pulmonary embolism (1.4%), adrenal insufficiency (1.1%) and pneumonia (1.1%). Fatal adverse reactions occurring in 3 (0.9%) patients who received OPDIVO as a single agent; these included pneumonitis (n=2) and myasthenia gravis. In Checkmate 040, serious adverse reactions occurred in 59% of patients receiving OPDIVO with YERVOY (n=49). Serious adverse reactions reported in ≥4% of patients were pyrexia, diarrhea, anemia, increased AST, adrenal insufficiency, ascites, esophageal varices hemorrhage, hyponatremia, increased blood bilirubin, and pneumonitis. In Attraction-3, serious adverse reactions occurred in 38% of patients receiving OPDIVO (n=209). Serious adverse reactions reported in ≥2% of patients who received OPDIVO were pneumonia, esophageal fistula, interstitial lung disease, and pyrexia. The following fatal adverse reactions occurred in patients who received OPDIVO: interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock (0.5%), esophageal fistula (0.5%), gastrointestinal hemorrhage (0.5%), pulmonary embolism (0.5%), and sudden death (0.5%). In Checkmate 577, serious adverse reactions occurred in 33% of patients receiving OPDIVO (n=532). A serious adverse reaction reported in ≥2% of patients who received OPDIVO was pneumonitis. A fatal reaction of myocardial infarction occurred in one patient who received OPDIVO. In Checkmate 648, serious adverse reactions occurred in 62% of patients receiving OPDIVO in combination with chemotherapy (n=310). The most frequent serious adverse reactions reported in ≥2% of patients who received OPDIVO with chemotherapy were pneumonia (11%), dysphagia (7%), esophageal stenosis (2.9%), acute kidney injury (2.9%), and pyrexia (2.3%). Fatal adverse reactions occurred in 5 (1.6%) patients who received OPDIVO in combination with chemotherapy; these included pneumonitis, pneumatosis intestinalis, pneumonia, and acute kidney injury. In Checkmate 648, serious adverse reactions occurred in 69% of patients receiving OPDIVO in combination with YERVOY (n=322). The most frequent serious adverse reactions reported in ≥2% who received OPDIVO in combination with YERVOY were pneumonia (10%), pyrexia (4.3%), pneumonitis (4.0%), aspiration pneumonia (3.7%), dysphagia (3.7%), hepatic function abnormal (2.8%), decreased appetite (2.8%), adrenal insufficiency (2.5%), and dehydration (2.5%). Fatal adverse reactions occurred in 5 (1.6%) patients who received OPDIVO in combination with YERVOY; these included pneumonitis, interstitial lung disease, pulmonary embolism, and acute respiratory distress syndrome. In Checkmate 649, serious adverse reactions occurred in 52% of patients treated with OPDIVO in combination with chemotherapy (n=782). The most frequent serious adverse reactions reported in ≥2% of patients treated with OPDIVO in combination with chemotherapy were vomiting (3.7%), pneumonia (3.6%), anemia (3.6%), pyrexia (2.8%), diarrhea (2.7%), febrile neutropenia (2.6%), and pneumonitis (2.4%). Fatal adverse reactions occurred in 16 (2.0%) patients who were treated with OPDIVO in combination with chemotherapy; these included pneumonitis (4 patients), febrile neutropenia (2 patients), stroke (2 patients), gastrointestinal toxicity, intestinal mucositis, septic shock, pneumonia, infection, gastrointestinal bleeding, mesenteric vessel thrombosis, and disseminated intravascular coagulation. In Checkmate 76K, serious adverse reactions occurred in 18% of patients receiving OPDIVO (n=524). Adverse reactions which resulted in permanent discontinuation of OPDIVO in >1% of patients included arthralgia (1.7%), rash (1.7%), and diarrhea (1.1%). A fatal adverse reaction occurred in 1 (0.2%) patient (heart failure and acute kidney injury). The most frequent Grade 3-4 lab abnormalities reported in ≥1% of OPDIVO-treated patients were increased lipase (2.9%), increased AST (2.2%), increased ALT (2.1%), lymphopenia (1.1%), and decreased potassium (1.0%).
Common Adverse Reactions
In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse reactions (≥20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (62%), diarrhea (54%), rash (53%), nausea (44%), pyrexia (40%), pruritus (39%), musculoskeletal pain (32%), vomiting (31%), decreased appetite (29%), cough (27%), headache (26%), dyspnea (24%), upper respiratory tract infection (23%), arthralgia (21%), and increased transaminases (25%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO arm (n=313) were fatigue (59%), rash (40%), musculoskeletal pain (42%), diarrhea (36%), nausea (30%), cough (28%), pruritus (27%), upper respiratory tract infection (22%), decreased appetite (22%), headache (22%), constipation (21%), arthralgia (21%), and vomiting (20%). In Checkmate 238, the most common adverse reactions (≥20%) reported in OPDIVO-treated patients (n=452) vs ipilimumab-treated patients (n=453) were fatigue (57% vs 55%), diarrhea (37% vs 55%), rash (35% vs 47%), musculoskeletal pain (32% vs 27%), pruritus (28% vs 37%), headache (23% vs 31%), nausea (23% vs 28%), upper respiratory infection (22% vs 15%), and abdominal pain (21% vs 23%). The most common immune-mediated adverse reactions were rash (16%), diarrhea/colitis (6%), and hepatitis (3%). In Checkmate 816, the most common (>20%) adverse reactions in the OPDIVO plus chemotherapy arm (n=176) were nausea (38%), constipation (34%), fatigue (26%), decreased appetite (20%), and rash (20%). In Checkmate 77T, the most common adverse reactions (reported in ≥20%) in patients receiving OPDIVO in combination with chemotherapy (n= 228) were anemia (39.5%), constipation (32.0%), nausea (28.9%), fatigue (28.1%), alopecia (25.9%), and cough (21.9%). In Checkmate 227, the most common (≥20%) adverse reactions were fatigue (44%), rash (34%), decreased appetite (31%), musculoskeletal pain (27%), diarrhea/colitis (26%), dyspnea (26%), cough (23%), hepatitis (21%), nausea (21%), and pruritus (21%). In Checkmate 9LA, the most common (>20%) adverse reactions were fatigue (49%), musculoskeletal pain (39%), nausea (32%), diarrhea (31%), rash (30%), decreased appetite (28%), constipation (21%), and pruritus (21%). In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. In Checkmate 743, the most common adverse reactions (≥20%) in patients receiving OPDIVO plus YERVOY were fatigue (43%), musculoskeletal pain (38%), rash (34%), diarrhea (32%), dyspnea (27%), nausea (24%), decreased appetite (24%), cough (23%), and pruritus (21%). In Checkmate 214, the most common adverse reactions (≥20%) reported in patients treated with OPDIVO plus YERVOY (n=547) were fatigue (58%), rash (39%), diarrhea (38%), musculoskeletal pain (37%), pruritus (33%), nausea (30%), cough (28%), pyrexia (25%), arthralgia (23%), decreased appetite (21%), dyspnea (20%), and vomiting (20%). In Checkmate 9ER, the most common adverse reactions (≥20%) in patients receiving OPDIVO and cabozantinib (n=320) were diarrhea (64%), fatigue (51%), hepatotoxicity (44%), palmar-plantar erythrodysaesthesia syndrome (40%), stomatitis (37%), rash (36%), hypertension (36%), hypothyroidism (34%), musculoskeletal pain (33%), decreased appetite (28%), nausea (27%), dysgeusia (24%), abdominal pain (22%), cough (20%) and upper respiratory tract infection (20%). In Checkmate 025, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were fatigue (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 205 and 039, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=266) were upper respiratory tract infection (44%), fatigue (39%), cough (36%), diarrhea (33%), pyrexia (29%), musculoskeletal pain (26%), rash (24%), nausea (20%) and pruritus (20%). In Checkmate 141, the most common adverse reactions (≥10%) in patients receiving OPDIVO (n=236) were cough (14%) and dyspnea (14%) at a higher incidence than investigator’s choice. In Checkmate 275, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=270) were fatigue (46%), musculoskeletal pain (30%), nausea (22%), and decreased appetite (22%). In Checkmate 274, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=351) were rash (36%), fatigue (36%), diarrhea (30%), pruritus (30%), musculoskeletal pain (28%), and urinary tract infection (22%).In Checkmate 901, the most common adverse reactions (≥20%) were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, and peripheral neuropathy. In Checkmate 8HW, the most common adverse reactions reported in ≥20% of patients treated with OPDIVO in combination with ipilimumab were fatigue, diarrhea, pruritus, abdominal pain, musculoskeletal pain, and nausea. In Checkmate 8HW the most common adverse reaction reported in ≥20% of patients treated with OPDIVO as a single agent, were fatigue, diarrhea, abdominal pain, pruritus, and musculoskeletal pain. In Checkmate 040, the most common adverse reactions (≥20%) in patients receiving OPDIVO with YERVOY (n=49), were rash (53%), pruritus (53%), musculoskeletal pain (41%), diarrhea (39%), cough (37%), decreased appetite (35%), fatigue (27%), pyrexia (27%), abdominal pain (22%), headache (22%), nausea (20%), dizziness (20%), hypothyroidism (20%), and weight decreased (20%). In Attraction-3, the most common adverse reactions (≥20%) in OPDIVO-treated patients (n=209) were rash (22%) and decreased appetite (21%). In Checkmate 577, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=532) were fatigue (34%), diarrhea (29%), nausea (23%), rash (21%), musculoskeletal pain (21%), and cough (20%). In Checkmate 648, the most common adverse reactions (≥20%) in patients treated with OPDIVO in combination with chemotherapy (n=310) were nausea (65%), decreased appetite (51%), fatigue (47%), constipation (44%), stomatitis (44%), diarrhea (29%), and vomiting (23%). In Checkmate 648, the most common adverse reactions reported in ≥20% of patients treated with OPDIVO in combination with YERVOY were rash (31%), fatigue (28%), pyrexia (23%), nausea (22%), diarrhea (22%), and constipation (20%). In Checkmate 649, the most common adverse reactions (≥20%) in patients treated with OPDIVO in combination with chemotherapy (n=782) were peripheral neuropathy (53%), nausea (48%), fatigue (44%), diarrhea (39%), vomiting (31%), decreased appetite (29%), abdominal pain (27%), constipation (25%), and musculoskeletal pain (20%). In Checkmate 76K, the most common adverse reactions (≥20%) reported with OPDIVO (n=524) were fatigue (36%), musculoskeletal pain (30%), rash (28%), diarrhea (23%) and pruritis (20%).
Surgery Related Adverse Reactions
In Checkmate 77T, 5.3% (n=12) of the OPDIVO-treated patients who received neoadjuvant treatment, did not receive surgery due to adverse reactions. The adverse reactions that led to cancellation of surgery in OPDIVO- treated patients were cerebrovascular accident, pneumonia, and colitis/diarrhea (2 patients each) and acute coronary syndrome, myocarditis, hemoptysis, pneumonitis, COVID-19, and myositis (1 patient each).
Please see U.S. Full Prescribing Information for OPDIVO and YERVOY.
Clinical Trials and Patient Populations
Checkmate 227-previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 649–previously untreated advanced or metastatic gastric cancer, gastroesophageal junction and esophageal adenocarcinoma; Checkmate 577–adjuvant treatment of esophageal or gastroesophageal junction cancer; Checkmate 238–adjuvant treatment of patients with completely resected Stage III or Stage IV melanoma; Checkmate 76K–adjuvant treatment of patients 12 years of age and older with completely resected Stage IIB or Stage IIC melanoma; Checkmate 274–adjuvant treatment of urothelial carcinoma; Checkmate 275–previously treated advanced or metastatic urothelial carcinoma; 8HW: Previously Checkmate 142–MSI-H or dMMR metastatic colorectal cancer in combination with YERVOY; 8HW: Previously Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent; Attraction-3–esophageal squamous cell carcinoma; Checkmate 648-previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma in combination with chemotherapy; Checkmate 648-previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma combination with YERVOY; Checkmate 040–hepatocellular carcinoma, in combination with YERVOY; Checkmate 743–previously untreated unresectable malignant pleural mesothelioma, in combination with YERVOY; Checkmate 037–previously treated metastatic melanoma; Checkmate 066-previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non- squamous non-small cell lung cancer; Checkmate 816–neoadjuvant non-small cell lung cancer, in combination with platinum-doublet chemotherapy; Checkmate 77T–Neoadjuvant treatment with platinum-doublet chemotherapy for non-small cell lung cancer followed by single-agent OPDIVO as adjuvant treatment after surgery; Checkmate 901–Adult patients with unresectable or metastatic urothelial carcinoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 025–previously treated renal cell carcinoma; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 9ER–previously untreated renal cell carcinoma, in combination with cabozantinib; Checkmate 205/039–classical Hodgkin lymphoma
Bristol Myers Squibb: Creating a Better Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research platforms uniquely position the company to approach cancer from every angle.
Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
About Targeted Protein Degradation and Distinct CELMoD Agents
Targeted protein degradation (TPD) is a core strength for Bristol Myers Squibb built on more than two decades of scientific expertise, providing new avenues to degrade therapeutically relevant proteins that were previously considered "undruggable." We are the only company that has successfully developed and commercialized protein degrader agents – immunomodulatory drugs (IMiD®) which helped establish the current standard of care in the treatment of multiple myeloma. We are building on this foundation with several investigational protein degraders in clinical trials, leveraging three different modalities including oral CELMoD agents, ligand-directed degraders (LDDs), and degrader antibody conjugates (DACs). This three-pronged approach allows us to match the right therapeutic modality to a molecular mechanism of action to modulate targets most effectively and ultimately provides more opportunities for potential breakthroughs that may offer meaningful new options for patients across a broad range of diseases, in and beyond hematology and oncology. Learn more about the science behind TPD at Bristol Myers Squibb here.
Bristol Myers Squibb: Unlocking the Full Potential of Cell Therapy
A pioneer in harnessing the immune system to fight cancer and an established leader in cell therapy, Bristol Myers Squibb is uniquely positioned to unlock the full potential of this technology across blood cancers and within new frontiers, including autoimmune disease.
Bristol Myers Squibb is currently the only company with two approved CAR T cell therapies with two distinct targets, available in major markets around the world. Our bold vision for the future is one in which hundreds of thousands of patients can be treated with cell therapy’s transformational potential.
The building blocks to realize this ambition - a promising and differentiated pipeline, extensive translational and clinical data sets, a deep bench of talent, and robust manufacturing capabilities - are in our cells. We are laser-focused on advancing the field of cell therapy toward a true revolution for patients. Learn more about the science behind cell therapy and ongoing progress at Bristol Myers Squibb here.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, X, YouTube, Facebook and Instagram.
Cautionary Statement Regarding Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2024, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.
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临床结果免疫疗法临床2期临床1期ASH会议
100 项与 甲氧聚二醇重组人促红素 相关的药物交易
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| - | 甲氧聚二醇重组人促红素 |
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 贫血 | 中国 | 2018-04-28 | |
| 肾性贫血 | 日本 | 2011-04-22 | |
| 伴随慢性肾病的贫血 | 澳大利亚 | 2009-07-28 | |
| 慢性肾衰竭贫血 | 欧盟 | 2007-07-20 | |
| 慢性肾衰竭贫血 | 冰岛 | 2007-07-20 | |
| 慢性肾衰竭贫血 | 列支敦士登 | 2007-07-20 | |
| 慢性肾衰竭贫血 | 挪威 | 2007-07-20 |
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 慢性肾病，V期 | 临床3期 | 美国 | 2007-03-01 | |
| 腹膜透析并发症 | 临床3期 | 日本 | 2007-02-01 | |
| 肾病 | 临床3期 | 日本 | 2007-01-01 | |
| 慢性肾病 | 临床3期 | 美国 | 2004-02-01 | |
| 慢性肾病 | 临床3期 | 巴西 | 2004-02-01 | |
| 慢性肾病 | 临床3期 | 加拿大 | 2004-02-01 | |
| 慢性肾病 | 临床3期 | 捷克 | 2004-02-01 | |
| 慢性肾病 | 临床3期 | 法国 | 2004-02-01 | |
| 慢性肾病 | 临床3期 | 德国 | 2004-02-01 | |
| 慢性肾病 | 临床3期 | 希腊 | 2004-02-01 |
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| 研究 | 分期 | 人群特征 | 评价人数 | 分组 | 结果 | 评价 | 发布日期 |
|---|
N/A | 229 | (Peritoneal Dialysis (PD)) | 膚鹽築鬱構艱繭憲積顧(範製簾願構淵襯鏇襯選) = 121 PD patients (68%) and 36 HD patients (69%) had ≥ 1 hospitalization, of whom 102/121 (84%) and 32/36 (89%), respectively, had non-elective hospitalizations. Median hospitalization surveillance time/patient was 13.5 months in the PD and 18.3 months in the HD cohorts. The most frequent causes for non-elective hospitalization were infections, reported as a cause in 56/177 (32%) patients in the PD cohort and 14/52 (27%) in the HD cohort and technique complications, in 41/177 (23%) patients in the PD cohort and 20/52 (38%) in the HD cohort. 艱齋範願選壓積壓繭艱 (夢觸繭憲壓壓膚簾憲簾 ) 更多 | 积极 | 2022-05-03 | ||
临床2期 | - | C.E.R.A. SC every 4 weeks | 醖蓋獵鏇構構願壓衊襯(獵築蓋糧簾築鑰獵簾鏇) = 顧淵鑰蓋網積夢壓糧齋 廠願廠夢鹽糧糧顧淵夢 (鏇選鹽襯蓋醖範膚齋願, 1.03) 更多 | 积极 | 2022-05-03 | ||
临床2期 | 40 | 顧艱齋窪鑰願願遞夢築(夢糧膚糧艱襯觸遞齋簾) = 廠顧築鬱壓齋餘網簾膚 糧遞觸鹹獵淵簾憲鹹蓋 (築網襯淵蓋顧衊夢選壓, 0.51) 更多 | - | 2022-03-07 | |||
临床4期 | 2,818 | 製築獵構繭選齋鏇糧範(衊廠繭積糧觸築糧夢襯): HR = 1.06 (95% CI, 0.94 ~ 1.19) 更多 | - | 2019-12-06 | |||
Reference Erythropoiesis-Stimulating Agents | |||||||
临床4期 | 87 | (Pre-dialysis, Sea Level) | 製築壓網觸願醖鬱艱醖(鬱構壓鹽憲製積鬱簾築) = 網鬱遞衊餘鹹餘選鑰窪 壓襯醖淵製窪壓餘簾糧 (願網簾膚衊艱窪選積壓, 69.0) 更多 | - | 2018-12-27 | ||
(Dialysis, Sea Level) | 製築壓網觸願醖鬱艱醖(鬱構壓鹽憲製積鬱簾築) = 餘淵鬱淵構廠築齋製遞 壓襯醖淵製窪壓餘簾糧 (願網簾膚衊艱窪選積壓, 214.2) 更多 | ||||||
临床4期 | 2,825 | (Erythropoiesis Stimulating Agents) | 願餘積夢襯積衊鹹選蓋(窪襯夢壓顧繭遞蓋鑰鑰) = 艱選觸獵鹹醖淵窪憲襯 網鹽衊醖窪繭壓願遞淵 (蓋願觸簾鹹襯製壓鬱膚, 餘構醖鹹壓範糧淵範製 ~ 蓋構範鏇蓋壓觸獵積醖) 更多 | - | 2018-08-15 | ||
(Methoxy Polyethylene Glycol-Epoetin Beta) | 願餘積夢襯積衊鹹選蓋(窪襯夢壓顧繭遞蓋鑰鑰) = 齋廠觸願窪夢艱窪獵窪 網鹽衊醖窪繭壓願遞淵 (蓋願觸簾鹹襯製壓鬱膚, 繭窪簾遞觸襯餘夢醖夢 ~ 膚壓範製夢憲顧餘廠鏇) 更多 | ||||||
临床2期 | 64 | 構鏇觸鏇蓋遞製獵鑰艱(選願積遞齋衊製製構鹹) = 製餘淵衊顧遞廠醖鏇夢 窪觸製遞襯襯願範糧鏇 (齋製築簾齋憲簾鑰網鹹, -0.45 ~ 0.26) 更多 | 积极 | 2018-01-06 | |||
临床2期 | 64 | (MIRCERA Group 1: Intermediate-Conversion-Factor Group) | 鑰蓋選願繭襯艱壓鹽製(選簾鏇鏇艱淵餘糧餘窪) = 繭艱窪膚築積淵獵廠糧 鏇構憲膚製糧鑰遞醖餘 (鑰觸鬱鏇醖鬱鹽憲鏇鹽, 0.496) 更多 | - | 2017-09-08 | ||
(MIRCERA Group 2: High-Conversion-Factor Group) | 鑰蓋選願繭襯艱壓鹽製(選簾鏇鏇艱淵餘糧餘窪) = 壓鏇蓋遞鬱願鏇鑰齋構 鏇構憲膚製糧鑰遞醖餘 (鑰觸鬱鏇醖鬱鹽憲鏇鹽, 0.493) 更多 | ||||||
临床2期 | 235 | erythropoiesis-stimulating agents | 觸壓壓齋網遞製簾觸鏇(簾構構築艱蓋鬱餘積獵) = 憲鏇範鹹鹽願窪鹽壓蓋 遞夢憲齋壓願淵製築衊 (糧醖憲簾憲夢遞窪簾衊, -2.2 ~ 3.8) 更多 | 不佳 | 2017-02-01 | ||
Placebo | 觸壓壓齋網遞製簾觸鏇(簾構構築艱蓋鬱餘積獵) = 構鬱簾淵鑰簾餘齋網襯 遞夢憲齋壓願淵製築衊 (糧醖憲簾憲夢遞窪簾衊, -2.0 ~ 3.2) 更多 | ||||||
临床3期 | 490 | 網觸獵鹽製範淵獵繭鹹 = 鏇築鹽艱鑰襯夢獵簾鏇 壓夢憲簾壓範淵積醖衊 (網獵選觸製獵顧網憲鑰, 衊繭構網繭築積齋憲積 ~ 鏇淵積糧醖醖襯蓋齋膚) 更多 | - | 2017-01-20 | |||
(Darbepoetin Alfa) | 網觸獵鹽製範淵獵繭鹹 = 夢製積構鹽觸積遞艱鑰 壓夢憲簾壓範淵積醖衊 (網獵選觸製獵顧網憲鑰, 餘齋蓋淵積襯製獵淵繭 ~ 醖鏇憲願壓廠廠網選繭) 更多 |
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