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更新于：2025-12-06
Cabozantinib (s)-Malate
苹果酸卡博替尼
更新于：2025-12-06
概要
基本信息
药物类型 小分子化药 |
别名 cabozantinib、Cabozantinib Malate、Cabozantinib s-malate (USAN) + [10] |
作用方式 抑制剂、拮抗剂 |
作用机制 AXL抑制剂(AXL受体酪氨酸激酶抑制剂)、RET抑制剂(酪氨酸蛋白激酶受体RET抑制剂)、ROS1抑制剂(原癌基因酪氨酸蛋白激酶ROS抑制剂) |
在研适应症 |
原研机构 |
最高研发阶段批准上市 |
首次获批日期 美国 (2012-11-29), |
最高研发阶段(中国)临床3期 |
特殊审评优先审评 (美国)、突破性疗法 (美国)、快速通道 (美国)、孤儿药 (美国) |
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结构/序列
分子式C32H30FN3O10 |
InChIKeyHFCFMRYTXDINDK-WNQIDUERSA-N |
CAS号1140909-48-3 |
关联
274
项与 苹果酸卡博替尼 相关的临床试验NCT06900595
A Phase II Study of Cabozantinib in Combination With Cemiplimab (Cabo-Cemiplimab) Versus Cabozantinib Alone in Adolescents and Adults With Advanced Adrenocortical Cancer
This phase II trial compares the effect of giving cabozantinib with or without cemiplimab in patients with adrenocortical cancer that has spread to nearby tissue or lymph nodes (locally advanced), and that cannot be removed by surgery (unresectable) or that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Cabozantinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib with cemiplimab may kill more tumor cells in patients with locally advanced unresectable or recurrent/metastatic adrenocortical cancer.
开始日期2026-07-19 |
申办/合作机构 |
NCT07187869
Modulation of the Bone Immune Microenvironment Following Cabozantinib Treatment of Bone Metastatic Clear Cell Renal Cell Carcinoma: Proof of Concept Study
The goal of our study is to explore how treatments affect the bone immune microenvironment and determine the best treatment options for patients with metastatic kidney cancer to the bone. This could prevent skeletal complications and improve patient outcomes.
开始日期2026-03-31 |
NCT07077161
Cabozantinib Dose Skipping as an Alternative to Dose Reductions
The goal of this study is to determine if an alternative cabozantinib dosing regimens results in a similar drug exposure compared to the standard regimens in patients with metastatic renal cell carcinoma (mRCC). All dosages of cabozantinib (20 ,40, 60mg) have the same price, and cabozantinib is eliminated very slowly by the body. This means that using fewer tablets could potentially lead to cost savings, while remaining equally effective.
The main questions it aims to answer are:
* Is the drug exposure from our experimental regimens similar to the standard dosing regimens?
* Do the experimental regimens affect the number of side effect and the patients' quality of life?
Participants will:
* Take cabozantinib according to either the experimental or standard dosage regimen for 4 weeks
* After 4 weeks: visit the clinic to collect some blood samples and complete two questionnaires.
* 1 and 3 days after this visit: visit the clinic to collect 1 blood sample.
* The day after the hospital visit: switch to the other dosing regimen and according to that regimen for another 4 weeks.
* After 4 weeks: visit the clinic to collect some blood samples and complete two questionnaires
* 1 and 3 days after this visit: visit the clinic to collect 1 blood sample.
The main questions it aims to answer are:
* Is the drug exposure from our experimental regimens similar to the standard dosing regimens?
* Do the experimental regimens affect the number of side effect and the patients' quality of life?
Participants will:
* Take cabozantinib according to either the experimental or standard dosage regimen for 4 weeks
* After 4 weeks: visit the clinic to collect some blood samples and complete two questionnaires.
* 1 and 3 days after this visit: visit the clinic to collect 1 blood sample.
* The day after the hospital visit: switch to the other dosing regimen and according to that regimen for another 4 weeks.
* After 4 weeks: visit the clinic to collect some blood samples and complete two questionnaires
* 1 and 3 days after this visit: visit the clinic to collect 1 blood sample.
开始日期2026-01-01 |
申办/合作机构- |
100 项与 苹果酸卡博替尼 相关的临床结果
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100 项与 苹果酸卡博替尼 相关的转化医学
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100 项与 苹果酸卡博替尼 相关的专利（医药）
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2,359
项与 苹果酸卡博替尼 相关的文献（医药）2026-02-01·INTERNATIONAL JOURNAL OF CANCER
Metastatic osteosarcoma, patterns of care and outcomes of patients in a real‐life national setting over a decade
Article
作者: Narciso, Berengère ; Bonneau, Maeva ; Marec‐Berard, Perrine ; Gantzer, Justine ; Bellio, Hélène ; Toulmonde, Maud ; Bompas, Emmanuelle ; Duong, Romain ; Goldwasser, François ; Brahmi, Mehdi ; Piperno‐Neumann, Sophie ; Le Cesne, Axel ; Brunet, Maxime ; Boudou‐Rouquette, Pascaline ; Dinart, Derek ; Winter, Sarah ; Gaspar, Nathalie ; Jean‐Denis, Myriam ; Nannini, Simon ; Anract, Philippe ; Valentin, Thibaud ; Reich, Mathilde ; Bellera, Carine ; Perret, Raul ; Berchoud, Juliane
Abstract:
Metastatic osteosarcoma (MOS) has a poor prognosis, and few treatment options. This multicentre observational study provides real‐world data on treatment patterns of patients with MOS in France. The primary objective was to describe treatment modalities of patients with MOS aged ≥12 years treated in 11 reference network centers. Secondary objectives were to assess time to next treatment (TTNT), overall survival (OS) and prognostic factors for TTNT and OS. From 2008 to 2018, 262 patients with MOS were included; 88 patients were metastatic at diagnosis, and 174 patients had a metastatic relapse. Median age at diagnosis was 26 (12–86). A total of 227 (86.6%) patients received systemic treatment in the metastatic setting, and 75 (28.6%) patients received more than two lines. Overall, 153 (58.4%) patients underwent at least a loco‐regional procedure, and 50 patients (19.1%) participated in a clinical trial in the metastatic setting. Median OS from metastasis diagnosis was 21.5 months [95% CI 18.9–27.0], 23.0 months [95% CI 15.0–31.1] in the synchronous cohort, and 21.4 months [95% CI 18.7–29.7] in the metachronous cohort. Median TTNT was 8.2 months [95% CI 6.7–9.9], 5.7 months [95% CI 4.2–7.2], 3.7 months [95% CI 3.0–4.3], and 2.9 months [95% CI 1.8–3.9] in first, second, third, and fourth line. It was 7.6 months [95% CI 5.1–12.5], 6 months [95% CI 3.6–8.7], and 4.8 months [95% CI 2.9–7.5] for tyrosine kinase inhibitors such as regorafenib or cabozantinib in first, second, and third line. In MOS, the benefit of chemotherapy after first line is limited. TKIs show encouraging activity from first line. Inclusion in clinical trials should be prioritized.
2026-01-01·DRUG DISCOVERY TODAY
Integrated therapies for targeting the microenvironment of hepatocellular carcinoma
Review
作者: Cheetiyar, Anusha Lakshmi ; Bhaskar, Lvks ; Ghanta, Mohan Krishna ; Nagaraju, Ganji Purnachandra ; Karunakaran, Shriraam
Hepatocellular carcinoma (HCC) microenvironments (MEs) are composed of immune and non-immune components that drive tumor progression and treatment resistance. This narrative review summarizes recent progress in systemic therapies combined with liver-directed approaches as a new frontier in metastatic HCC treatment. Immune checkpoint inhibitors (tremelimumab and durvalumab) in combination with small- molecule agents (lenvatinib and cabozantinib) enhance T-cell activation and improve progression-free survival in HCC. Epigenetic inhibitors and RNA-based therapeutics target the HCC ME and increase the efficacy of immunotherapy. Additionally, cellular therapy targeting agents like glypican-3 (GPC3) for chimeric antigen receptor T (CAR-T) cells have shown promising results. HCC ME has distinct immune subtypes exhibiting different responses to treatments, which complicates biomarker selection and treatment timing. Personalized therapy based on ME is the future path in HCC management.
2025-12-03·JAPANESE JOURNAL OF CLINICAL ONCOLOGY
Efficacy and safety of a reduced starting dose of cabozantinib (20 mg) plus nivolumab for renal cell carcinoma in real-world practice
Article
作者: Nagaoka, Kotaro ; Pae, Sangjon ; Toma, Kohei ; Onoda, Yusuke ; Watanabe, Yuri ; Sakamoto, Shinichi ; Yokochi, Fumiya ; Saito, Shinpei ; Imamura, Yusuke ; Yamada, Yasutaka ; Ando, Keisuke ; Sato, Kodai ; Sazuka, Tomokazu
Abstract:
Background:
In systemic treatment for renal cell carcinoma, some patients require dose reduction to prevent adverse events. However, there is currently almost no evidence to support a reduced starting dose for cabozantinib + nivolumab (C + N) in clinical practice.
Methods:
We retrospectively analyzed single-institution data for patients with renal cell carcinoma with an assessed response to C + N. The starting dose was determined during a multidisciplinary meeting for each patient by considering the following patient characteristics: age, performance status, body weight, and medical history. In all cases, the dosage and schedule of nivolumab could not be modified. Efficacy and adverse events were examined.
Results:
Fourteen and eighteen patients, respectively, received 20 (reduced dose) and 40 mg (standard dose) of cabozantinib in C + N treatment. The median age was 79.5 years in the reduced-dose group and 69.5 years in the normal-dose group (P < .0001). The objective response rate was 71% in the reduced-dose group and 78% in the normal-dose group (P = .6807). There were no significant differences in progression-free survival and overall survival, nor in the overall and grade ≥ 3 adverse events rates between the groups. Liver dysfunction of any grade occurred significantly more frequently in the normal-dose group (61%) versus the reduced-dose group (21%) (P = .0247).
Conclusions:
A 20-mg starting dose of cabozantinib in C + N therapy can achieve almost the same efficacy as a normal starting dose for patients who are hesitant to start treatment at the normal 40-mg dose.
778
项与 苹果酸卡博替尼 相关的新闻（医药）2025-12-04
本文刊登在《现代泌尿外科杂志》2025年11期专家论坛栏目，点击文末的“阅读原文”按钮，直达本刊官网，下载本文PDF。
引用此文：张海梁,叶定伟,艾合太木江·安外尔.肾癌靶免联合药物安全性管理[J].现代泌尿外科杂志,2025,30(11):911-917.
作者简介
张海梁：主任医师、教授、博士生导师,复旦大学附属华东医院泌尿外科主任,中国泌尿肿瘤精准诊疗与微创手术领域领军专家,长期专注于肾癌、前列腺癌及膀胱癌的综合治疗与机器人辅助手术研究。主持多项国家自然科学基金及省部级重点课题,在泌尿系统肿瘤的免疫微环境与耐药机制研究方面取得重要突破,成果发表于《Molecular Cancer》《Journal of Hematology & Oncology》《Molecular Cancer》《Cancer Research》《Nature Communications》《Theranostics》等国际顶级期刊。现任上海抗癌协会泌尿肿瘤专业委员会副主任委员、中国抗癌协会泌尿男生殖系统肿瘤专委会秘书长等学术职务。任《Phenomics》青年编委、《Journal of the National Cancer Center》客座编辑、《Journal of Clinical Oncology》中文版编委。曾获国家科学技术进步奖一等奖、上海市科技进步一等奖、教育部科技进步一等奖等多项殊荣。
肾癌靶免联合药物安全性管理
张海梁，叶定伟，艾合太木江·安外尔
复旦大学附属肿瘤医院泌尿外科,上海市泌尿生殖系统肿瘤研究所,复旦大学上海医学院肿瘤学系
摘要：近年来，肾癌靶向治疗与免疫治疗联合应用已成为各大指南推荐的晚期肾癌治疗方案。然而，靶免联合治疗虽然有显著的疗效和生存优势，但也伴随着多种不容忽视的不良反应。因此，如何在靶免联合治疗中有效管理不良反应，确保患者的治疗安全性，成为肾癌临床治疗中的核心问题之一。本文主要介绍肾癌靶免联合药物治疗中的常见不良反应及其管理策略，探讨了不良反应的早期识别、监测方法、个体化治疗方案的设计及未来发展趋势，旨在为临床实践提供切实可行的安全性管理指导，同时探索靶免联合治疗的发展方向。
关键词：肾癌；靶向治疗；免疫治疗；不良反应；安全性管理
随着靶向治疗和免疫疗法的不断发展，肾癌(renal cell carcinoma, RCC)的治疗策略发生了显著变化。靶向药物如血管内皮生长因子(vascular endothelial growth factor, VEGF)抑制剂(舒尼替尼、培唑帕尼、阿昔替尼、仑伐替尼、伏罗尼布、安罗替尼等)和哺乳动物雷帕霉素靶蛋白(mechanistic target of rapamycin, mTOR)抑制剂(依维莫司)以及免疫检查点抑制剂[程序性死亡受体-1(programmed cell death-1,PD-1)抑制剂，如帕博利珠单抗、纳武利尤单抗等，程序性死亡-配体1(programmed cell death ligand 1,PD-L1)抑制剂 ,如阿替利珠单抗、阿维鲁单抗等]已成为临床上治疗晚期RCC的主流药物[1-3]。此外，靶向治疗联合免疫治疗，展现出优异的疗效，显著改善了患者的生存期和生活质量。然而，这种联合治疗模式也带来了新的挑战，尤其是安全性管理方面。靶免联合治疗过程中，患者可能会同时或异时出现免疫相关不良反应(immune-related adverse events, irAEs)和靶向治疗相关不良反应(如高血压、肝损伤等)[4-5]。如何高效、精准地管理这些不良反应，已经成为提高治疗效果和改善患者生活质量的重要任务。本文系统回顾并总结RCC靶免联合治疗的不良反应管理现状，分析其常见不良反应的特点、相关不良反应管理策略及未来的研究方向。
PART.1
RCC靶免联合治疗的现状
1.1 输尿管腔内治疗
1.1 靶向治疗药物概述
靶向治疗药物的应用是近年来肿瘤治疗的重大突破之一，它通过特异性作用于肿瘤细胞特定分子靶点，干扰其生长、增殖和转移过程，从而达到精准杀伤肿瘤细胞的效果，已经成为治疗包括RCC在内多种癌症的标准疗法。在RCC的靶向治疗中，针对血管生成和细胞生长调控的两大类靶点药物尤为重要：一类是以VEGF及VEGF受体(VEGF receptor, VEGFR)为靶点的药物，另一类是以mTOR为靶点的药物。
VEGF及VEGFR是调控肿瘤新生血管生成的关键因子，肿瘤细胞通过分泌VEGF促进血管生成，为肿瘤的生长提供营养支持[6]。目前，以舒尼替尼、培唑帕尼、阿昔替尼、仑伐替尼、索拉非尼、伏罗尼布、安罗替尼等为代表的小分子酪氨酸蛋白抑制剂，可有效抑制VEGFR信号通路，对晚期RCC的疗效显著。mTOR通路是肿瘤细胞生长、增殖和存活的重要调控通路[7]。mTOR抑制剂通过阻断这一通路，能够有效抑制肿瘤细胞增殖，延缓肿瘤进展。依维莫司作为最常用的mTOR抑制剂，是晚期RCC的二线标准治疗药物，适用于既往接受舒尼替尼或索拉非尼治疗失败的成人患者。临床研究显示，其可通过抑制mTOR信号通路和肿瘤细胞增殖，显著延长患者的无进展生存期(progression-free survival, PFS)。1.2 免疫治疗药物概述
免疫治疗是通过激活和增强机体免疫反应，利用患者自身的免疫系统识别并清除肿瘤细胞的一种方式。20世纪90年代，免疫检查点抑制剂，如PD-1、PD-L1、细胞毒性T淋巴细胞相关蛋白4(cytotoxic T-lymphocyte-associated protein 4,CTLA-4)逐渐成为癌症治疗的重要组成部分，也为RCC的治疗带来了革命性进展。
纳武利尤单抗和帕博利珠单抗是目前全球范围内应用最广泛的PD-1抑制剂，其可通过解除肿瘤细胞对T细胞的免疫逃逸机制，从而恢复机体免疫系统对肿瘤的攻击[8]。研究表明，PD-1/PD-L1抑制剂在RCC等多种癌症中疗效显著。而CTLA-4类免疫检查点抑制剂如伊匹单抗，可通过阻断T细胞上的CTLA-4分子，以增强T细胞的免疫功能。伊匹单抗与纳武利尤单抗的联合方案(“O+Y”方案)在CheckMate 214研究中显示出显著的临床获益，而“O+Y”方案已被美国国立综合癌症网络(National Comprehensive Cancer Network, NCCN)指南推荐为晚期RCC的一线治疗选择之一[9]。1.3 RCC靶免联合治疗的进展
随着PD-1/PD-L1抑制剂的相继上市，免疫治疗已经成为RCC治疗的常规选择之一。CheckMate 025临床试验结果显示，与依维莫司相比，纳武利尤单抗在延长晚期RCC二线治疗生存期方面具有显著优势[中位总生存期(overall survival, OS)25个月vs. 19.6个月][10]。KEYNOTE-426临床试验发现，帕博利珠单抗联合阿昔替尼相较于舒尼替尼单药治疗的中位PFS更长(12.9个月vs.8.3个月)[11],该研究为免疫治疗在RCC中的应用奠定了基础，并改写了晚期RCC一线治疗的指南推荐。CheckMate 9ER研究是一项关键的Ⅲ期临床试验，评估了纳武利尤单抗(抗PD-1抗体)联合卡博替尼(Cabozantinib, 抗VEGFR2抑制剂)在晚期RCC中的疗效，研究结果显示，联合方案显著提高了患者的PFS和OS,该方案在所有预设亚组中均显示出一致获益，特别是在接受过抗血管生成治疗的患者中，联合治疗相较于舒尼替尼单药治疗，具有更好的疗效和安全性[12]。上述成果为免疫检查点抑制剂联合靶向药物治疗在RCC中的应用奠定了基础。Renotorch研究是一项随机、开放、Ⅲ期研究，主要用于评估特瑞普利单抗(Toripalimab)联合阿昔替尼一线治疗中、高危不可切除或转移性RCC患者的有效性和安全性，对于未接受任何治疗的中高危转移性RCC患者，Toripalimab联合阿昔替尼方案无论是在次要研究终点还是主要研究终点指标方面均具有优异的疗效获益，并且安全性可控[13]。CLEAR研究是一项国际多中心Ⅲ期临床试验，比较了阿维鲁单抗(抗PD-L1抗体)联合阿昔替尼(抗VEGFR抑制剂)与单用舒尼替尼在治疗晚期RCC中的效果，研究结果显示，阿维鲁单抗联合阿昔替尼治疗相较于单用舒尼替尼，在PFS和OS方面均表现出显著的临床优势[14],故该联合方案被认为是一种具有潜力的一线治疗方案，尤其是在VEGF通路和免疫通路双重靶向的背景下，疗效更加持久。
上述研究表明，免疫检查点抑制剂与靶向治疗的联合方案在RCC的治疗中取得了显著进展。尽管各项研究的具体药物组合有所不同，但其共同的特点是通过同时作用于肿瘤的免疫逃逸机制和血管生成通路，特别是对一些高风险或耐药患者，具有显著的疗效。然而，安全性仍然是值得考量的重要因素之一，尤其是在联合治疗中可能增加的irAEs和靶向相关不良反应，需要进一步关注和管理。
PART.2
RCC靶免联合治疗的不良反应管理
2.1 免疫相关不良反应2.1.1免疫相关不良反应的定义
irAEs是指由免疫检查点(如PD-1、PD-L1、CTLA-4)抑制剂等免疫治疗药物引起的不良反应，其通过解除肿瘤细胞对免疫系统的抑制作用，激活机体免疫系统，从而增强抗肿瘤免疫反应。然而，免疫检查点抑制剂作用范围广，激活的T细胞、B细胞、树突状细胞等也可能误伤正常组织，导致免疫系统自我攻击，引发多器官系统的损害，包括皮肤、胃肠道、内分泌系统、肝脏、肺脏等，严重时甚至危及生命。值得注意的是，免疫检查点抑制剂的疗效与不良反应之间存在一定的关联。研究表明，部分患者出现irAEs可能与更好的抗肿瘤疗效有关，提示免疫系统激活程度与治疗效果密切相关。然而，这种关联并非绝对，部分患者可能因免疫应答过度而引发严重不良反应，甚至需要中断治疗。因此，临床实践中需要在疗效与安全性之间寻求平衡，通过早期识别、及时干预和个体化管理，最大限度地发挥免疫治疗的疗效，同时降低irAEs的发生率和严重程度[15-16]。2.1.2免疫相关不良反应的危害2.1.2.1器官损害
irAEs可能导致多种器官的损害，严重时会引发不可逆的损伤，如免疫性心肌炎、免疫性肺炎、免疫性肝炎、免疫性肾炎等，如果不及时处理，可能导致器官功能衰竭并危及生命。2.1.2.2影响治疗耐受性
irAEs可能影响患者继续接受免疫治疗的耐受性，部分不良反应甚至需要停药或中断治疗，从而影响治疗效果。2.1.2.3生存率下降
尽管免疫治疗的疗效显著，但严重的irAEs会对患者的生存期产生负面影响。研究发现，irAEs的严重程度和持续时间与患者的生存期有一定关联。2.1.2.4对生活质量的影响
irAEs可能引发长期的健康问题，影响患者的生活质量，如免疫性甲状腺功能不全、肾上腺功能不全、糖尿病、免疫性皮疹、关节炎等症状可能对患者日常生活造成显著影响。2.1.3常见irAEs及其发生率
irAEs种类繁多，常见的有皮肤反应、肝脏损伤、肺部疾病、胃肠道症状等[17]。表1列出了部分常见irAEs及其发生率、临床表现。
表1 常见免疫相关不良反应及其发生率、临床表现
2.2 靶向治疗相关不良反应2.2.1靶向治疗相关不良反应的定义和机制
靶向治疗不良反应是指由靶向治疗药物引起的不良反应，靶向药物通过特定的分子靶点作用于肿瘤细胞，阻止其增殖或扩散。然而，靶向药物对肿瘤细胞的特异性不足时会产生脱靶效应，同样可能作用于正常组织中的相关靶点，导致不良反应的发生。靶向治疗的不良反应通常与靶点的选择、药物的使用剂量及患者的个体差异有关。以RCC治疗中最常用的抗VEGFR药物为例，其通过抑制VEGFR来阻止肿瘤的血管生成，但也可能影响正常血管，导致高血压、出血等不良反应[21-22]。2.2.2靶向治疗相关不良反应的危害2.2.2.1器官损害
一些靶向药物可能导致器官损害，如肝功能损害(尤以mTOR抑制剂为典型)、心脏损害、高血压等。长期不加以干预的情况下，可能对患者的整体健康状况造成不良影响。2.2.2.2血液系统不良反应
靶向药物可能导致贫血、白细胞减少或血小板减少等血液系统问题，严重时可能影响治疗的持续性和患者的生存期。2.2.2.3影响疗效
患者因靶向药物产生不良反应而减量，无法达到有效的血药浓度，导致治疗效果减弱，无法有效控制肿瘤，进而影响临床疗效。2.2.3常见靶向治疗相关不良反应及其发生率
高血压、手足综合征、胃肠道不良反应、出血、肝功能损害、蛋白尿等是靶向治疗常见的不良反应，其中手足综合征发生率较高为30%～40%[23]。上述各种不良反应的发生率及临床表现详见表2。
表2 常见靶向治疗相关不良反应及其发生率、临床表现
2.3 其他不良反应
除了靶向治疗和免疫治疗药物的特定不良反应外，肿瘤治疗过程中还可能会出现一些其他的不良反应，影响治疗的效果和患者的生活质量，如疲劳、贫血等。疲劳是所有癌症治疗中最常见的不良反应之一，几乎所有肿瘤患者都会经历不同程度的疲劳。疲劳可能由于肿瘤本身、化疗、靶向治疗或免疫治疗等多种因素引起，发生率为40%～70%[23，26]。贫血会影响患者的生活质量，严重时甚至需要输血治疗，其在接受治疗的RCC患者中较为常见，尤其是在接受靶向治疗的患者中，发生率为30%～40%[23-24]。
PART.3
不良反应的分级及处理指引
在靶向治疗和免疫治疗过程中，不良反应的严重性和影响因患者个体差异而不同。因此，不良反应的处理策略应根据不良反应的严重程度进行分级，并依据分级采取不同的干预措施。不良反应的分级通常遵循美国国家癌症研究所(National Cancer Institute, NCI)常见不良事件标准(Common Terminology Criteria for Adverse Events, CTCAE)[27]。该标准将不良反应分为5个等级(表3)。
表3 靶向治疗及免疫治疗过程中不良反应的分级标准
PART.4
不良反应的监测、早期识别及处理方式
4.1 不良反应的监测原则
不良反应的监测是RCC靶向治疗和免疫治疗过程中至关重要的环节，及时发现并有效处理不良反应能够显著提高治疗的安全性与患者的生活质量[28]。不良反应的监测应遵循以下原则：①个体化监测。根据患者的治疗方案、疾病状态及既往健康情况，制定个性化的不良反应监测计划。每例患者可能对药物的反应不同，因此需要结合其治疗方案(如靶向药物类型、免疫治疗方案)进行有针对性的监测。②系统化监测。建立系统化的不良反应监测流程，定期检查和跟踪患者的健康状况，特别是可能与治疗相关的器官(如心脏、肝脏、肺部、肾脏、胃肠道等)。监测应定期进行，也应根据患者出现的临床症状进行动态调整。③早期发现、及时干预。不良反应的早期发现对于减少治疗相关危害至关重要，能有效避免不良反应的恶化，减少患者的住院率和治疗中断率。④多学科合作。不良反应的监测与管理应通过多学科协作进行，特别是在复杂不良反应出现时(如irAEs),不同科室的医生应共同参与治疗和管理。⑤患者自我监测与报告。除了临床监测外，患者及其家属也应接受相关培训，了解可能出现的不良反应及其初期症状，应主动报告不良反应，帮助医生及时调整治疗方案。4.2 不良反应早期识别的意义
早期识别不良反应有助于降低严重不良反应的风险、改善治疗顺应性、保护患者的生活质量、优化治疗方案。首先，及时识别并管理不良反应，能有效防止其进一步恶化，避免发生危及生命的严重不良反应，如免疫性肺炎、肝炎等。其次，不良反应的早期干预能够降低患者因不良反应过重而中断治疗的可能性，从而提高治疗的整体效果和患者的生存率。再次，早期识别并处理能够减少不良反应对患者日常生活的干扰，提高治疗期间的舒适度。最后，通过对不良反应的监测与管理，医生可以根据患者的反应调整治疗方案，使治疗更符合患者的需求，避免药物使用不当或用药剂量不当。4.3 靶免联合治疗中不良反应的监测手段及处理策略
靶向治疗和免疫治疗常见的不良反应涉及多个系统，需要采取多种检查手段进行监测，如血液常规、肝功能、肾功能检查等。而irAEs如免疫性肝炎、肺炎、皮炎、肠炎的处理需按照不良反应等级进行。Grade 1:通常不需要特殊处理，但需定期监测；Grade 2:暂停免疫治疗，使用低剂量的糖皮质激素(如泼尼松)控制症状，待症状缓解后可恢复治疗；Grade 3及以上：立即暂停免疫治疗，使用高剂量糖皮质激素治疗(如泼尼松、甲基泼尼松龙),在症状恢复后评估是否需要重新开始免疫治疗[29-31]。其他不良反应的处理详见表4。
表4 靶免联合治疗中不良反应的监测手段及处理策略
4.4 不良反应的多学科联合处理策略
在靶向治疗和免疫治疗过程中，不良反应的出现常常涉及多个器官，特别是irAEs, 可能同时影响皮肤、胃肠、肺部、肝脏等多个器官。因此，不良反应的处理不仅依赖于单一学科的治疗，还需要通过多学科合作的方式优化不良反应管理，确保治疗效果并最大限度地减少不良反应。
靶向治疗与免疫治疗的多学科协同管理对优化患者治疗至关重要。首先，由于靶向治疗和免疫治疗常引发多系统不良反应(如免疫性肺炎、肝炎、肠炎等),需要不同领域的专家共同参与诊断和治疗，实现对复杂症状的全面评估与精准干预。其次，免疫治疗相关不良反应具有急性发作和快速进展的特点，多学科协作能通过快速信息共享和联合判断显著提高早期识别效率，从而早期干预，避免不良反应的进一步恶化。再次，每例患者的治疗方案和不良反应不同，因此不良反应的管理需要根据患者的具体情况进行调整。多学科专家可以制定个体化的治疗和管理方案，提高不良反应处理的针对性和效果。最后，针对其可能导致的长期或持续性的健康问题(如免疫性内分泌紊乱或慢性肾损伤),多学科联合治疗有助于从早期着手，进行长期监测和管理，最大限度地减少不良反应对患者生存质量的远期影响。多学科联合处理模式不仅提升了不良反应处理的效率，也为患者生存质量提供了保障。
PART.5
不良反应管理策略和管理展望
随着靶向治疗和免疫治疗在RCC等恶性肿瘤治疗中的广泛应用，不良反应的管理日益成为患者治疗过程中的关键挑战。尽管目前已有多种不良反应管理策略和多学科联合治疗模式，但随着新药物的不断推出和治疗方案的不断发展，靶向治疗与免疫治疗的不良反应管理仍面临一系列复杂的问题。未来，随着技术进步和临床经验的积累，不良反应的预防、识别与管理将趋向精准化和个性化。5.1 个体化不良反应管理策略的进一步完善
随着精准医学的发展，未来靶向治疗和免疫治疗的不良反应管理将更趋于个体化。基因组学和蛋白质组学将有助于预测患者的治疗反应，例如通过深入了解患者基因突变、免疫环境、药物代谢等特征，可以预测免疫治疗或靶向治疗的不良反应风险，从而在治疗前制定个性化的不良反应管理方案。此外，药物基因组学的发展有望帮助优化靶向药物的剂量和选择，减少不良反应发生的可能性。
未来有关免疫治疗的研究可能聚焦于irAEs早期标志物的识别。通过液体活检或组织学检查，开发出能够检测免疫激活状态的生物标志物，为临床医生提供早期预警信号，从而能够在不良反应发生进展之前采取干预措施。5.2 靶向治疗与免疫治疗的联合方案的不良反应管理
随着靶向治疗和免疫治疗联合应用的逐渐普及，如何有效管理联合治疗带来的复合不良反应是未来的一个关键挑战。靶向治疗和免疫治疗具有不同的不良反应谱，二者联合使用可能会导致意料之外的不良反应，如irAEs和靶向药物引起的心血管、肝脏或胃肠道不良反应的交叉影响。因此，未来的不良反应管理策略不仅要根据单一药物的不良反应进行调整，还需要系统性地考虑两者联合治疗的潜在风险。
目前，多学科联合治疗已经成为管理复合不良反应的重要手段，未来，随着更多临床研究的开展，可能会有更多基于联合治疗的不良反应管理标准和指南出台。这些指南将为不同治疗方案的不良反应评估、监测和干预提供更加细致的指导，从而确保联合治疗的安全性和效果。5.3 不良反应监测对临床试验和新药研发的推动作用
未来临床试验的设计不仅要关注疗效，还需要注重药物不良反应的评估和管理，尤其是在治疗靶点和机制上较为创新的药物。新药研发过程中，应加强对其产生的不良反应机制的研究，尽可能减少药物对正常组织的毒性作用，提高安全性。
此外，越来越多的临床试验将聚焦于不同治疗组合的不良反应谱，以便为临床提供更好的指导。例如，靶向治疗与免疫治疗联合应用的不良反应管理方案需要通过大规模的临床研究数据来优化，并制定标准化的处理流程，以便广泛应用到临床实践中。
PART.6
小 结
靶向联合免疫治疗在改善RCC患者生存期和生活质量方面展现出显著的疗效，但也伴随着多种不良反应。合理有效的不良反应管理对于确保患者的安全性、提高治疗效果及减轻治疗负担具有至关重要的作用。当前的不良反应管理策略强调早期识别、个体化干预和多学科合作，为临床实践提供了宝贵的指导。未来的研究应进一步探索如何优化不良反应监测和管理策略，发展更具针对性的个体化治疗方法，以最大程度发挥靶免联合治疗的疗效，并减少不良反应对患者的负面影响。
参考文献：
[1]YOUNG M,JACKSON-SPENCE F,BELTRAN L,et al.Renal cell carcinoma[J].Lancet,2024,404(10451):476-491.
[2] LJUNGBERG B,ALBIGES L,ABU-GHANEM Y,et al.European Association of Urology Guidelines on renal cell carcinoma:the 2022 update[J].Eur Urol,2022,82(4):399-410.
[3] TANG Y,SHEN Y,WANG Z,et al.Next-generation sequencing-guided personalized therapy in renal cell carcinoma[J].Holistic Integrative Oncol,2024,3(1):4.
[4] MOTZER R,ALEKSEEV B,RHA SY,et al.Lenvatinib plus Pembrolizumab or Everolimus for advanced renal cell carcinoma[J].N Engl J Med,2021,384(14):1289-1300.
[5] CHOUEIRI TK,POWLES T,BUROTTO M,et al.Nivolumab plus Cabozantinib versus Sunitinib for advanced renal-cell carcinoma[J].N Engl J Med,2021,384(9):829-841.
[6] FOGLI S,PORTA C,DEL RM,et al.Optimizing treatment of renal cell carcinoma with VEGFR-TKIs:a comparison of clinical pharmacology and drug-drug interactions of anti-angiogenic drugs[J].Cancer Treat Rev,2020,84:101966.
[7] FENG YN,XIAO L,XIE GY.Adjuvant everolimus after renal cell carcinoma nephrectomy[J].Lancet,2024,404(10465):1809-1810.
[8] WU Q,JIANG L,LI SC,et al.Small molecule inhibitors targeting the PD-1/PD-L1 signaling pathway[J].Acta Pharmacol Sin,2021,42(1):1-9.
[9] KORMAN AJ,GARRETT-THOMSON SC,LONBERG N.The foundations of immune checkpoint blockade and the Ipilimumab approval decennial[J].Nat Rev Drug Discov,2022,21(7):509-528.
[10] MOTZER RJ,ESCUDIER B,GEORGE S,et al.Nivolumab versus everolimus in patients with advanced renal cell carcinoma:updated results with long-term follow-up of the randomized,open-label,phase 3 CheckMate 025 trial[J].Cancer,2020,126(18):4156-4167.
[11] BEDKE J,RINI BI,PLIMACK ER,et al.Health-related quality of life analysis from KEYNOTE-426:Pembrolizumab plus Axitinib versus Sunitinib for advanced renal cell carcinoma[J].Eur Urol,2022,82(4):427-439.
[12] MOTZER RJ,POWLES T,BUROTTO M,et al.Nivolumab plus cabozantinib versus sunitinib in first-line treatment for advanced renal cell carcinoma(CheckMate 9ER):long-term follow-up results from an open-label,randomised,phase 3 trial[J].Lancet Oncol,2022,23(7):888-898.
[13] YAN XQ,YE MJ,ZOU Q,et al.Toripalimab plus Axitinib versus Sunitinib as first-line treatment for advanced renal cell carcinoma:RENOTORCH,a randomized,open-label,phaseⅢ study[J].Ann Oncol,2024,35(2):190-199.
[14] MOTZER RJ,ROBBINS PB,POWLES T,et al.Avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma:biomarker analysis of the phase 3 JAVELIN Renal 101 trial[J].Nat Med,2020,26(11):1733-1741.
[15] BAXI S,YANG A,GENNARELLI RL,et al.Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs:systematic review and meta-analysis[J].BMJ,2018,360:k793.
[16] POTO R,TROIANI T,CRISCUOLO G,et al.Holistic approach to immune checkpoint inhibitor-related adverse events[J].Front Immunol,2022,13:804597.
[17] YAN T,YU L,ZHANG J,et al.Achilles' Heel of currently approved immune checkpoint inhibitors:immune related adverse events[J].Front Immunol,2024,15:1292122.
[18] MOTZER RJ,PENKOV K,HAANEN J,et al.Avelumab plus Axitinib versus Sunitinib for advanced renal-cell carcinoma[J].N Engl J Med,2019,380(12):1103-1115.
[19] MOTZER RJ,RINI BI,MCDERMOTT DF,et al.Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma:extended follow-up of efficacy and safety results from a randomised,controlled,phase 3 trial[J].Lancet Oncol,2019,20(10):1370-1385.
[20] CHOUEIRI TK,TOMCZAK P,PARK SH,et al.Adjuvant Pembrolizumab after nephrectomy in renal-cell carcinoma[J].N Engl J Med,2021,385(8):683-694.
[21] LEE N,LEE JL,LEE JY.Analysis of anti-angiogenesis-related adverse events associated with vascular endothelial growth factor receptor-tyrosine kinase inhibitors(VEGFR-TKIs)in patients with metastatic renal cell carcinoma[J].Target Oncol,2023,18(2):247-255.
[22] NARAYAN V,LIU T,SONG Y,et al.Early increases in blood pressure and major adverse cardiovascular events in patients with renal cell carcinoma and thyroid cancer treated with VEGFR TKIs[J].J Natl Compr Canc Netw,2023,21(10):1039-1049.
[23] MOTZER RJ,HUTSON TE,TOMCZAK P,et al.Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma[J].J Clin Oncol,2009,27(22):3584-3590.
[24] POWLES T,PLIMACK ER,SOULIERES D,et al.Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma(KEYNOTE-426):extended follow-up from a randomised,open-label,phase 3 trial[J].Lancet Oncol,2020,21(12):1563-1573.
[25] MOTZER RJ,ESCUDIER B,MCDERMOTT DF,et al.Nivolumab versus Everolimus in advanced renal-cell carcinoma[J].N Engl J Med,2015,373(19):1803-1813.
[26] CHOUEIRI TK,POWLES T,PELTOLA K,et al.Belzutifan versus everolimus for advanced renal-cell carcinoma[J].N Engl J Med,2024,391(8):710-721.
[27] BASCH E,REEVE BB,MITCHELL SA,et al.Development of the National Cancer Institute's patient-reported outcomes version of the common terminology criteria for adverse events(PRO-CTCAE)[J].J Natl Cancer Inst,2014,106(9):dju244.
[28] EIGENTLER TK,HASSEL JC,BERKING C,et al.Diagnosis,monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy[J].Cancer Treat Rev,2016,45:7-18.
[29] MOTZER RJ,TANNIR NM,MCDERMOTT DF,et al.Nivolumab plus Ipilimumab versus Sunitinib in advanced renal-cell carcinoma[J].N Engl J Med,2018,378(14):1277-1290.
[30] HAANEN J,OBEID M,SPAIN L,et al.Management of toxicities from immunotherapy:ESMO clinical practice guideline for diagnosis,treatment and follow-up[J].Ann Oncol,2022,33(12):1217-1238.
[31] WANCHOO R,KARAM S,UPPAL NN,et al.Adverse renal effects of immune checkpoint inhibitors:a narrative review[J].Am J Nephrol,2017,45(2):160-169.
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2025-12-02
原研药🆚仿制药原创发明 vs 合法复刻 【原研药】- 10年+研发，数十亿投入- 价格昂贵，专利保护20年- 创新担当，设定黄金标准
【仿制药】- 快速上市，成本大幅降低- 价格仅原研30%-80%- 惠民先锋，促进药物可及性👩🏻⚕️记住：活性成分一样！但辅料和外观可以不同。关键是有“药品一致性评价”为仿制药质量护航！
55家大型外国药企汇总🌈美国（14家）：辉瑞、强生、礼来 、美国默克（默沙东）、百时美施贵宝、雅培、安进、吉利德 、艾伯维、百健、艾尔建、再生元 、新基、亚力兄制药……日本（12家）：武田 、第一三共、安斯泰来、大冢制药、中外制药、卫材、住友制药、三菱田边、协和发酵麒麟、小野药品、 参天制药 、帝人制药、东和药品……瑞士（6家）：罗氏、诺华、辉凌、萌蒂、雪兰诺（被默克收购）雀巢……法国（3家）：赛诺菲 施维雅 益普生德国（4家）：拜耳 德国默克 费森尤斯卡比 勃林格殷格翰英国（3家）：葛兰素史克 阿斯利康 夏尔（被武田收购）荷兰（2家）：迈兰、纽迪希亚意大利（1家）：美纳里尼印度（1家）：太阳制药南非（1家）：Aspen 爱施健以色列（1家）：梯瓦丹麦（2家）：诺和诺德、灵北制药比利时（1家）：优时比韩国（1家）：韩美药业澳大利亚（1家）：CSL加拿大（1家）：威朗制药西班牙（1家）：盖立复
✨ 为什么敢说印度药靠谱？看完你就明白了🏆 第一梯队：全球规则的参与者太阳制药：印度“药王”，专科药强大，收购国际公司是家常便饭。雷迪博士：最早与国际接轨，对全球药监法规门儿清，质量体系过硬。西普拉：传奇企业，让全球用上低价抗艾药，吸入剂技术全球领先。
💪 第二梯队：供应链的支柱赫托集团：全球抗艾滋药核心供应商，只是不爱打广告。奥罗宾多：产品线极广，从原料到成品一条龙，是很多大药厂的幕后供应商。鲁宾：在呼吸、结核病等专科领域是专家，受主流市场认可。
🔬 第三梯队：技术创新的先锋百康：生物药领域的王者，技术门槛极高。Divi‘s实验室：顶级药企的“御用”原料供应商，质量是金字招牌。卡迪拉：能研发出DNA疫苗，创新能力毋庸置疑。 总结一下，让你放心的核心原因：1.法规严格：这些企业全面遵守WHO-GMP、美国FDA、欧盟EMA等国际最高生产规范。2.技术顶尖：在复杂的吸入剂、生物药、疫苗等领域都拥有全球领先技术。3.全球认可：它们的产品畅销欧美等全球最严格的市场，品质经过双重认证。 所以，许多印度版药和原研药有效成分相同，且出自这些国际巨头之手，其质量是值得信赖的理性选择。
💊 不只有印度！土耳其也是制药宝藏之地！提到海外药，别只盯着印度了！🇹🇷 土耳其作为横跨欧亚的桥梁，它的制药业水平超乎你想象——它可是众多全球顶尖药企的“欧洲生产基地”！ 今天就带大家盘点土耳其的十大药厂，看完你就明白为什么土耳其版本的药品值得信赖了！👇 🏆 第一部分：跨国巨头在土耳其的“王牌部队”这些公司你肯定听过，它们在土耳其设厂生产，标准全球统一！辉瑞、诺华（山德士）、阿斯利康、赛诺菲、拜耳：全是世界TOP级药企！它们在土耳其拥有生产基地和临床研究中心，产品供应欧洲及全球，品质无需置疑。
🌟 第二部分：土耳其本土的“精英代表队”本土药企同样强大，严格遵循国际标准，更是出口佼佼者！Abdi İbrahim：土国“药王”，产品线最广，正大力进军生物创新药。DEVA Holding：历史最久、规模最大，以高质量原料药和制剂闻名，是出口冠军。Bilim İlaç：“技术流”代表，专注慢性病研发，有自己的专利产品。Ilsan İlaç：专注高价值领域（如肿瘤药），与国际药企合作紧密。Nobel İlaç：仿制药巨头，拥有符合国际标准的生产设施。 💎 总结：选择土耳其药的信心来源1.高标准：无论是跨国巨头还是本土精英，均遵守欧盟GMP等国际严格生产规范。2.强监管：作为欧盟候选国和重要市场，土耳其的药品监管体系非常严格。3.国际化：本土企业大量出口欧美，其质量经过更严苛市场的检验。 因此，许多土耳其版药品与原研药同生产线、同标准生产，其质量是可靠的选择。
全球抗癌药市场正迎来一场静默革命。随着欧美药企专利悬崖逼近、仿制药需求激增，东南亚药企以“高性价比+国际认证”的组合拳，悄然成为抗癌药领域的破局者。从印度🇮🇳孟加拉🇧🇩的仿制药巨头到老挝的跨境合作先锋，东南亚药企正以创新模式和区域协同，重塑全球药品供应格局。
根据世界贸易组织（WTO）的规定，老挝作为欠发达成员国家，享有对发达国家医药产品和临床数据专利保护的豁免权。这意味着在老挝政府的有效监管下，该国的制药企业可以生产任意一款世界新药的仿制药。
代表企业：老挝卢修斯制药（Lucius Pharmaceutical）
2020年，卢修斯制药（老挝）有限公司在老挝的首都万象建立生产园区，公司配备有现代化管理团队，仿制药生产能力超过10亿片/年，覆盖抗肿瘤、心血管等200+药品品类，主要市场印度，中国，中东，东南亚，东欧，非洲等国家。
1.老挝卢修斯制药：全球仿制药领域的“价格屠夫”
定位：老挝仿制药领军企业，以“让全球患者买得起优质药”为使命。
核心优势：
生产规模：工厂占地2.5万㎡，年产能超10亿片，覆盖抗肿瘤、心血管等200+药品品类。
质量认证：通过WHO-GMP认证，建立全流程质量追溯体系，确保疗效与原研药一致。
研发创新：成功仿制多款高价原研药，如抗癌药阿达格拉西布（价格仅为原研1/10）和抗病毒药万赛维（性价比全球领先）。
全球化布局：产品远销50+国家，与中日韩、东南亚等十余国建立合作。
案例：针对抗癌药价格高昂问题，卢修斯通过技术突破打破垄断，让患者以更低成本获得生存希望。
2.老挝大熊制药：专注抗癌与血液病的“技术先锋”
定位：老挝最大血液及抗病毒药物生产商，以“革新癌症治疗”为目标。
核心优势：
技术突破：推出全球首款图卡替尼仿制药，精准打击癌细胞且副作用更小，首月免费用药政策减轻患者负担。
生产体系：2021年成立后快速扩张，依托先进设备实现高效生产。
患者服务：提供灵活支付与物流支持，覆盖东南亚及非洲市场。
未来方向：持续深耕抗癌领域，推动更多高性价比药物上市。
3.老挝联合制药：东南亚最大综合药厂的“中国基因”
定位：中老合资企业，打造覆盖研发、生产、销售的全产业链。
核心优势：
产能规模：新厂投资1.5亿美元，占地35万㎡，配备14条生产线，预计年产值50亿元。
产品矩阵：涵盖抗病毒药（如莫那匹拉韦）、抗癌药（劳拉替尼、索托拉西布）及保健品，满足多元化需求。
质量标准：通过GMP和ISO9001认证，原料药产能达500吨/年。
地理优势：依托赛色塔开发区政策，降低运输成本，辐射东南亚及非洲市场。
愿景：未来十年内成为亚洲领先的科技制药企业，推动区域医疗普惠。
4.老挝第二制药厂（PHARMA 2 VIENTIANE）
成立时间：较早成立的国有企业主要产品：涵盖广泛的药物，包括癌症、心血管和消化系统疾病的治疗药物。特点：凭借高质量和合理的价格在当地市场中占据了一定份额。
5.老挝东盟制药（Tlph）成立时间：较新成立的制药企业主要产品：主要提供抗生素、消炎药及癌症治疗药物。特点：专注于满足国内和区域市场需求，药品质量经过多项认证。
6.老挝磨丁元素制药（ElementoPharma）
成立时间：较新成立的制药企业主要产品：生产多种治疗药物，包括癌症药物和普通药物。特点：致力于提高药品可及性，以满足日益增长的医疗需求。
孟加拉常见仿制药企
1.孟加拉碧康制药（Beacon Pharma） 成立时间：2002年 主要产品：包括奥希替尼、达拉非尼等靶向药物，专注于癌症治疗。 特点：在国际市场上享有良好声誉，产品覆盖多个国家和地区。
2.孟加拉伊思达制药（Incepta） 成立时间：2003年 主要产品：提供多种抗癌药物、疫苗和生物药品。 特点：拥有现代化生产设施和严格的质量控制体系。
3.孟加拉热维奥制药（Genvio） 成立时间：2011年 主要产品：生产多种抗癌药物及其他治疗药物。 特点：以质量为核心，持续推进药品研发和生产。
4.孟加拉耀品国际（DIL） 成立时间：1995年 主要产品：专注于生产多种靶向药物，特别是在癌症领域。 特点：凭借良好的产品质量和信誉，在国内外市场赢得了广泛的信赖，致力于创新药物的研发。
5.珠峰制药（Everest Pharmaceutical）
珠峰制药是一家新兴的仿制药企业，其总部位于孟加拉首都达卡。珠峰制药实力强劲，已上市数十款仿制药，生产的仿制药覆盖传染病、肿瘤等领域，其主要产品包括：奥希替尼（肺癌）、艾乐替尼（肺癌）、乐伐替尼（肝癌）、奥拉帕尼（卵巢癌）、尼拉帕尼（卵巢癌）、艾曲波帕（升血小板）、拉罗替尼（广谱抗癌药、需NTRK基因融合）。
孟加拉凭借“强制仿制”政策红利，成为全球抗癌仿制药的核心供应地。从原料药到制剂一体化生产，抗肿瘤药成本较印度低15%，吸引全球药企代工合作。
改写格局的底层逻辑
成本重构
东南亚人力成本仅为中国的1/3，叠加自贸区税收优惠，抗癌药综合成本比印度低10%-15%。
政策协同
东盟统一药品注册制度（ACSS）加速10国市场准入，单款药物上市周期缩短至8个月。
需求驱动
东南亚癌症发病率年增5%，但抗癌药支付能力仅为欧美1/10，本土药企更擅于平衡疗效与可及性。
从仿制到创新，从区域到全球，东南亚药企正以“蚂蚁雄兵”姿态重构抗癌药价值链。这场变革不仅关乎成本与供给，更预示着全球医药产业权力格局的深刻迁移。
小编给大家汇总一下印度、孟加拉、缅甸、老挝等地的仿制药～
肺癌
（1）吉非替尼Gefitinib
（2）厄洛替尼Erlotinib
（3）AZD9291/奥希替尼Osimertinib
（4）埃克替尼Icotinib
（5）阿法替尼Afatinib
（6）达克替尼Dacomitinib
（7）克唑替尼Crizotinib
（8）劳拉替尼Lorlatinib
（9）布格替尼/布加替尼Brigatinib
（10）阿来替尼/艾乐替尼alectinib
（11）色瑞替尼Ceritinib
（12）恩曲替尼Entrectinib
（13）达拉非尼Dabrafenib
（14）维莫非尼Vemurafenib
（15）曲美替尼Trametinib
（16）卡马替尼Capmatinib
（17）塞尔帕替尼Selpercatinib
（18）安罗替尼Anlotinib
（19）拉罗替尼Larotrectinib
白血病
（1）维奈克拉/维奈托克Venetoclax
（2）米哚妥林Midostaurin
（3）恩西地平Enasidenib
（4）艾伏尼布Ivosidenib
（5）吉列替尼Gilteritinib
（6）奎扎替尼Quizartinib
（7）格拉吉布Glasdegib
实体瘤
（1）恩曲替尼Entrectinib
（2）拉罗替尼Larotrectinib
肝癌
（1）瑞格非尼Regorafenib
（2）索拉非尼Sorafenib
（3）仑伐替尼/乐伐替尼Lenvatinib
（4）卡博替尼/卡赞替尼Cabozantinib
乳腺癌
（1）哌柏西利/帕博西尼Palbociclib
（2）奥拉帕利/奥拉帕尼Olaparib
（3）瑞博西林Ribociclib
（4）玻玛西林Abemaciclib
（5）图卡替尼Tucatinib
（6）拉帕替尼Lapatinib
（7）来那替尼neratinib
（8）吡咯替尼Pyrotinib
（9）依维莫司Everolimus
（10）阿培利司Alpelisib
前列腺癌
（1）阿比特龙Abiraterone
（2）奥拉帕利Olaparib
卵巢癌
（1）尼拉帕利/尼拉帕尼Niraparib
（2）奥拉帕利/奥拉帕尼Olaparib
（3）氟唑帕利Fluzoparib
（4）帕米帕利Pamiparib
肾上腺皮质癌
（1）米托坦/密妥坦mitotane
升血小板药物
（1）艾曲泊帕/艾曲波帕Eltrombopag
（2）海曲泊帕Herombopag
（3）阿伐曲泊帕Avatrombopag
（4）芦曲泊帕Lusutrombopag
（5）罗米司亭Romiplostim
其他药物
（1）甲状腺癌：索拉非尼、乐伐替尼、卡博替尼
（2）肾癌：索拉非尼、乐伐替尼、卡博替尼
（3）胃癌：瑞格非尼
（4）淋巴瘤：依鲁替尼
（5）黑色素瘤：曲美替尼+达拉非尼、考比替尼
（6）多发性骨髓瘤：来那度胺、泊马度胺
（7）丙肝：索菲加达卡、吉二代、吉三代
（8）乙肝：TAF替诺福韦艾拉芬胺
（9）糖尿病：曲格列汀、恩格列净
（10）痛风：莱尔
（11）原发性胆汁胆管炎：奥贝胆酸
（12）特发性肺纤维化：尼达尼布
（13）预防血栓：艾普利
（14）心衰：莎韦坦
（15）肺动脉高压：玛希坦
（16）银屑病：阿普斯特
（17）减肥：奥利司他
（18）男科：他达拉非、西地拉非、达泊西汀
温馨提示：在医生指导下使用靶向药，切忌自行用药，否则有可能加重病情，具体遵照医生医嘱。
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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 苹果酸卡博替尼 相关的药物交易
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研发状态
批准上市
10 条最早获批的记录, 后查看更多信息
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 神经内分泌肿瘤 | 英国 | 2025-09-26 | |
| 高分化胰腺内分泌肿瘤 | 欧盟 | 2025-07-24 | |
| 高分化胰腺内分泌肿瘤 | 冰岛 | 2025-07-24 | |
| 高分化胰腺内分泌肿瘤 | 列支敦士登 | 2025-07-24 | |
| 高分化胰腺内分泌肿瘤 | 挪威 | 2025-07-24 | |
| 胰腺外神经内分泌肿瘤 | 澳大利亚 | 2018-01-19 | |
| 胰腺神经内分泌肿瘤 | 澳大利亚 | 2018-01-19 | |
| 分化型甲状腺癌 | 韩国 | 2017-09-26 | |
| 肾细胞癌 | 韩国 | 2017-09-26 | |
| 肝细胞癌 | 欧盟 | 2016-09-09 | |
| 肝细胞癌 | 冰岛 | 2016-09-09 | |
| 肝细胞癌 | 列支敦士登 | 2016-09-09 | |
| 肝细胞癌 | 挪威 | 2016-09-09 | |
| 晚期肾细胞癌 | 美国 | 2016-04-25 | |
| 甲状腺髓样癌 | 美国 | 2012-11-29 |
未上市
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 实体瘤 | 申请上市 | 中国 | 2020-09-28 | |
| 难治性分化型甲状腺癌 | 临床3期 | 美国 | 2024-08-22 | |
| 难治性甲状腺癌 | 临床3期 | 美国 | 2024-08-22 | |
| 转移性骨肉瘤 | 临床3期 | 美国 | 2023-03-03 | |
| 转移性骨肉瘤 | 临床3期 | 澳大利亚 | 2023-03-03 | |
| 转移性骨肉瘤 | 临床3期 | 加拿大 | 2023-03-03 | |
| 转移性骨肉瘤 | 临床3期 | 新西兰 | 2023-03-03 | |
| 晚期尿路上皮癌 | 临床3期 | 美国 | 2022-06-03 | |
| 晚期尿路上皮癌 | 临床3期 | 加拿大 | 2022-06-03 | |
| 膀胱癌 | 临床3期 | 美国 | 2022-06-03 |
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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 |
|---|
临床2期 | 21 | 製醖築網糧鹹夢憲鬱艱 = 鹽範範鹽鏇鹽糧鏇範鹽 艱積願衊襯獵窪淵構顧 (鑰獵範蓋齋願簾觸積構, 襯壓簾夢廠淵窪製獵醖 ~ 壓簾積範窪齋壓鏇艱鹽) 更多 | - | 2025-11-19 | |||
临床3期 | 晚期肾细胞癌 一线 | 540 | 糧製網鹽鬱餘憲鏇網築(艱簾憲壓顧糧範鹹範構) = 廠築製積艱顧鏇鑰餘蓋 鑰衊糧網夢鏇簾壓艱廠 (齋鬱淵顧鏇糧膚鏇獵鹹, 40.6 ~ 53.7) 更多 | 优效 | 2025-11-15 | ||
糧製網鹽鬱餘憲鏇網築(艱簾憲壓顧糧範鹹範構) = 鹽鹽築醖積醖鹹襯鹽選 鑰衊糧網夢鏇簾壓艱廠 (齋鬱淵顧鏇糧膚鏇獵鹹, 29.2 ~ 42.8) 更多 | |||||||
临床2期 | 肝细胞癌 新辅助 | 12 | 襯築壓顧糧憲蓋糧蓋鑰(觸築簾築鏇膚衊淵築膚) = 遞製鬱觸壓網憲艱範選 鏇齋範鬱鹹選艱製觸齋 (廠網壓鹹鹹衊膚夢糧蓋 ) | 积极 | 2025-11-05 | ||
临床2期 | 11 | 鹽鏇淵窪壓艱鹽壓壓鏇 = 積鬱憲糧構衊鹹觸獵鏇 構選構願範選餘鏇鬱醖 (蓋衊築窪廠製構糧壓壓, 壓餘齋窪鹽餘餘壓鏇網 ~ 構鹽獵選鑰築壓齋築襯) 更多 | - | 2025-10-31 | |||
N/A | 14 | 窪艱選製網繭製鏇願廠(衊鏇壓艱簾構選鹽夢顧) = 7.1% (G2) 醖網築蓋蓋範憲鹽膚觸 (積鹹廠築衊膚廠襯壓廠 ) 更多 | 积极 | 2025-10-17 | |||
N/A | 晚期肾细胞癌 一线 | 268 | 築艱築鑰餘願餘範繭顧(醖簾醖膚構製醖襯鹹遞) = similar 齋築齋餘餘積壓簾鹽鹽 (艱鏇鏇壓遞範壓選憲餘 ) 更多 | 积极 | 2025-10-17 | ||
临床2期 | 肝细胞癌 二线 | 40 | 鏇衊艱衊齋鹹蓋蓋憲構(窪蓋艱鹹衊獵蓋窪窪構) = 襯齋衊膚觸鹽糧構膚襯 積願膚網壓網範鹹繭蓋 (願醖蓋齋構膚餘夢夢淵 ) 更多 | 积极 | 2025-10-17 | ||
临床1/2期 | 42 | 觸繭醖夢鹽簾鹹鏇糧淵(襯製鹹構鏇築遞夢糧憲) = 廠餘蓋鹹膚觸蓋製蓋淵 齋鏇醖醖夢願鏇構齋淵 (獵繭窪繭網繭憲淵襯齋, 11.0 ~ 18.3) 更多 | 积极 | 2025-10-17 | |||
(pancreatic NET (panNET)) | 觸繭醖夢鹽簾鹹鏇糧淵(襯製鹹構鏇築遞夢糧憲) = 糧獵艱壓獵顧壓網憲艱 齋鏇醖醖夢願鏇構齋淵 (獵繭窪繭網繭憲淵襯齋 ) | ||||||
临床3期 | 49 | 膚鬱鏇簾願網窪積鹽遞(繭選獵鑰齋醖壓廠膚築) = fatigue (24%), hypertension (18%), diarrhea (9%), palmar plantar erythrodysesthesia (9%). 簾選壓構遞齋衊築觸壓 (觸製鏇願齋鬱鬱顧觸餘 ) 更多 | 积极 | 2025-10-17 | |||
placebo | |||||||
N/A | 1,736 | PRRT→Eve→Cabo | 憲襯鹹範選繭憲構壓齋(窪鹹鹽範顧鏇蓋鹹醖廠) = Delaying PRRT lowers the risk of MDS/AML, with the Eve→Cabo→PRRT strategy showing the lowest incidence (0.018). 鹹鹹壓簾糧製網艱鑰積 (鏇繭遞憲夢製艱壓鑰構 ) 更多 | 积极 | 2025-10-17 | ||
Eve→PRRT→Cabo |
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