Human Normal Immunoglobulin (The Japan Blood Products Organization)

在神经免疫领域中，重症肌无力（MG）的诊疗既需要扎实的理论基础，又需要精细的临床决策。MG的治疗目标已从单纯的“改善症状”转变为“达到最小症状表现或更好状态（MMS），同时实现无激素或最小剂量激素维持”。MG的药物治疗策略，从经典到前沿，从原则到细节有了好多认识的更新。 第一部分：治疗基石与核心原则 首先，我们必须明确：MG是一种由抗体介导、细胞免疫依赖、补体参与的获得性自身免疫病。治疗的根本是免疫调节/免疫抑制，而不仅仅是症状对抗。诊断时需明确抗体类型（AChR、MuSK、LRP4、血清阴性）、临床分型（如MGFA分型）及有无胸腺异常，这是所有治疗决策的起点。 核心治疗策略金字塔： 症状控制：胆碱酯酶抑制剂。 快速诱导缓解：免疫抑制（激素、静脉用丙种球蛋白、血浆置换）。 长期维持缓解：激素节省治疗（传统免疫抑制剂、靶向生物制剂）。 病因治疗：胸腺切除（针对AChR抗体阳性全身型MG，尤其伴胸腺瘤或药物难治者）。第二部分：药物详解与临床应用一、一线与基础用药 1. 胆碱酯酶抑制剂：症状治疗的“冲锋枪” 代表药物：溴吡斯的明。 作用机制：抑制乙酰胆碱酯酶，增加神经肌肉接头处ACh浓度，暂时改善肌力。 临床定位：所有类型MG的基础对症治疗，不能改变免疫病理过程。适用于新发诊断的初始症状控制、轻型眼肌型MG的长期治疗，以及重症患者免疫治疗起效前的“桥梁”。 用法用量： 起始：30-60mg，每日3-4次，根据症状调整。 最大剂量一般不超过480mg/日。剂量个体化差异大，“恰到好处”是关键。 操作要点： 必须向患者强调：这是“治标不治本”的药物，不能单独用于中重度MG。 副作用（腹痛、腹泻、分泌物增多）是剂量限制因素。可同时给予山莨菪碱或洛哌丁胺对抗。 MuSK-MG患者可能对其反应不佳或出现严重副作用，需慎用或小剂量起始。 危象时，可鼻饲或静脉注射（剂量约为口服的1/30）。 2. 糖皮质激素：免疫抑制的“主力军” 代表药物：泼尼松（龙）。 临床定位：最有效、最经济的一线免疫抑制药物，尤其用于快速控制病情。 用法用量（经典小剂量递增法，适用于门诊中重度患者）： 起始：10-20mg/日，每3-5天增加5-10mg，直至症状明显改善或达到目标剂量（通常为0.75-1 mg/kg/日，最大不超过100mg/日）。 病情稳定4-8周后，开始缓慢减量：每2-4周减5mg，至30mg/日后，减量速度需更慢（如每4-8周减2.5-5mg），寻找最低有效维持剂量（通常≤10mg/日）。 操作要点： 激素副作用教育至关重要：向患者详细解释库欣貌、血糖升高、高血压、骨质疏松、感染风险等，并提前预防（如补充钙剂、维生素D）。 警惕“一过性加重”：约50%患者在开始大剂量激素治疗的1-2周内可能出现一过性肌无力加重，甚至诱发危象。对中重度患者，起始治疗建议住院进行，或先使用IVIG/PE桥接。 监测血糖、血压、电解质、骨密度。二、二线/激素节省治疗（STS）药物 当激素减量困难、副作用无法耐受或需快速减停激素时启用。 1. 传统口服免疫抑制剂 硫唑嘌呤（AZA）： 定位：经典的激素节省剂，一线STS选择。 用法：起始25-50mg/日，每周增加25mg，直至目标剂量2-3 mg/kg/日。 关键操作：用药前检测TPMT基因型或活性。定期监测血常规、肝功能（前3个月每月，之后每3月）。起效慢（4-12个月），需耐心。 霉酚酸酯（MMF）： 定位：有效的一线STS，对淋巴细胞选择性较高。 用法：常用剂量1.5-2g/日，分两次口服。 注意：起效相对较快（2-6个月）。需监测血常规、感染风险。备孕女性禁用（致畸）。 他克莫司： 定位：对MuSK-MG有较好疗效；也用于难治性AChR-MG。 用法：起始1-2mg/日，根据血药浓度（目标谷浓度3-8ng/mL）和肾功能调整。 优势：起效较快（1-3个月）。监测肾功能、血糖、血压。 环孢素A：因肾毒性、高血压等副作用，现已较少作为一线STS。 甲氨蝶呤（MTX）：可作为经济有效的STS选择，尤其对AZA不耐受者。需补充叶酸，监测肝功、血常规。 2. 生物制剂（靶向治疗）这部分是近年来MG治疗的革命性进展。 CD20单抗：利妥昔单抗 定位：MuSK-MG的一线免疫抑制治疗；难治性AChR-MG的二线或三线选择。 用法：标准方案为375mg/m²，每周1次，连续4周；或固定剂量1000mg，2周后重复1次。后续按需或每6-12个月重复。 操作要点：用药前需筛查乙肝、结核。预防输液反应。监测B细胞水平（CD19+）指导再治疗。感染风险（尤其是PJP肺炎）需警惕，必要时预防。 补体C5抑制剂：依库珠单抗 定位：用于难治性AChR抗体阳性全身型MG成人患者。 机制：抑制补体终末膜攻击复合物形成，直接作用于病理核心。 用法：负荷剂量后每周维持，皮下注射剂型已上市更方便。 关键：必须进行脑膜炎球菌疫苗接种（至少提前2周）并全程预防。价格昂贵，需严格把握适应证。 FcRn拮抗剂（最新突破） Efgartigimod（艾加莫德α）：已在国内获批上市。皮下注射，每周一次，首个疗程4周，后续根据病情按周期使用。起效快（1-2周），安全性好。 Ravulizumab：长效C5抑制剂，每8周给药一次。 Batoclimab等：多个同类药物在临床试验中。 机制：通过阻断新生儿Fc受体（FcRn），加速致病性IgG抗体降解。 代表药物： 定位：为难治性、中重度MG提供了快速、强效、无需长期全面免疫抑制的新选择。可用于急性加重期的快速控制，或作为长期维持治疗。三、急性加重与危象的抢救治疗 静脉注射丙种球蛋白（IVIG）： 剂量：0.4g/kg/日，连续5天。 适用：中重度加重、术前准备、激素冲击前的桥接。起效时间约1-2周。 注意：肾功能不全、高凝状态患者慎用。 血浆置换（PE）： 方案：隔日一次，共5-6次。 适用：危象、快速恶化、对IVIG反应不佳者。起效最快（数天）。 注意：血流动力学不稳定者操作需谨慎。需建立中心静脉通路。第三部分：特殊人群用药考量 儿童MG： 溴吡斯的明是首选。激素仍是主流免疫治疗，但需严格评估生长发育影响。 IVIG和PE安全有效。AZA、MMF在儿童中应用数据增多。胸腺切除需更谨慎。 生物制剂应用需基于充分评估。 妊娠期与哺乳期MG： 原则：孕前达到稳定缓解是保障孕期平稳的关键。 相对安全：溴吡斯的明、激素、AZA（大量数据支持）、IVIG、PE。 避免使用：MMF、MTX、环孢素（致畸）。他克莫司数据有限，需权衡。 哺乳：溴吡斯的明、激素分泌至乳汁量极少，通常可哺乳。 老年MG： 合并症多，药物相互作用复杂。 免疫抑制剂选择需更关注肝肾功能、感染风险、骨质疏松基础。 他克莫司、MMF可能比AZA（骨髓抑制、肝损伤风险）更具优势。激素剂量宜更低，减量宜更缓。 警惕肿瘤筛查。 合并其他自身免疫病： 如合并甲状腺疾病、风湿病等，治疗需统筹兼顾，可能与风湿免疫科共管。免疫抑制剂（如MMF、AZA）可能“一石二鸟”。第四部分：临床实战场景与决策路径 场景一：新诊断的AChR抗体阳性全身型MG（MGFA IIb型） 起始：溴吡斯的明对症 + 口服泼尼松（小剂量递增）。若症状较重，可住院启动治疗，或先用IVIG桥接再启动激素。 维持：症状稳定后（约4-8周），在激素减量前，加用AZA或MMF作为激素节省剂。 评估胸腺：CT/MRI检查，若伴胸腺瘤，计划胸腺切除；若无胸腺瘤但药物控制不佳，可考虑胸腺切除。 难治情况：若上述方案效果不佳，评估依从性后，升级为他克莫司，或启动靶向治疗（如FcRn拮抗剂、利妥昔单抗）。 场景二：MuSK-MG患者 慎用/小剂量起始溴吡斯的明。 免疫抑制首选：利妥昔单抗是一线选择，疗效卓越。若不可及，激素联合他克莫司是有效的口服方案。 对IVIG反应可能优于PE。 场景三：MG危象（呼吸衰竭） 立即转入ICU，呼吸支持是首位。 急性期治疗“二选一”：PE（优先）或IVIG。 同时启动大剂量激素冲击（甲泼尼龙500-1000mg/日，3-5天后改为口服）。 感染灶的排查与控制至关重要。MG的治疗已进入“精准靶向、个体化全程管理”的时代。我们的工具箱日益丰富： 基石仍是溴吡斯的明和激素。 骨干是各类传统免疫抑制剂，需熟知其特性。 尖刀是各类生物制剂，为难治性患者带来曙光。 成功的治疗离不开：准确的初始评估、清晰的治疗目标、耐心的剂量滴定、细致的副作用监测、持续的患者教育以及多学科协作（呼吸科、ICU、胸外科、康复科）。

Follow-up data from CARTITUDE-4 show at least 80 percent of as-treated standard-risk patients remained progression and treatment-free following a single infusion as early as second line Data suggest stronger immune fitness in earlier lines may be associated with longer progression free survival ORLANDO, Fla., Dec. 6, 2025 /PRNewswire/ -- Johnson & Johnson (NYSE: JNJ) announced today updated results from the Phase 3 CARTITUDE-4 study supporting durable treatment-free remissions as early as second line treatment with CARVYKTI® (ciltacabtagene autoleucel; cilta-cel). In 80 percent of as-treated patients with relapsed or refractory multiple myeloma (RRMM) and standard-risk cytogenetics who were treated with CARVYKTI® as early as first relapse, the disease did not progress and no further treatment was required at 2.5 years (30 months).1 These results add to the body of clinical and real-world experience established across more than 9,000 patients treated with CARVYKTI® globally.1 Additional translational analyses demonstrated that patients receiving CARVYKTI® in earlier lines had improved immune fitness, which suggests a correlation with longer progression-free survival (PFS).1 These data (Abstracts #92, #94) were featured in oral presentations at the 2025 American Society of Hematology (ASH) Annual Meeting. "These data suggest that a single infusion of CARVYKTI for standard-risk patients may provide additional benefit to patients as early as second line of therapy," said Luciano J. Costa, M.D., Ph.D.,* Professor of Medicine at the University of Alabama and principal investigator of the CARTITUDE-4 study. "Treating patients with multiple myeloma after first relapse offers the opportunity to achieve deeper and more durable responses, shifting the treatment paradigm closer to the possibility of long-term remission and, ultimately, cure." "Our goal is to treat patients as early as possible, when they have the best chance for lasting remission," said Jordan Schecter, M.D., Vice President, Research & Development, Multiple Myeloma, Johnson & Johnson Innovative Medicine. "With more than 9,000 patients treated globally, CARVYKTI has demonstrated robust efficacy as soon as first relapse and is the first and only CAR-T to significantly extend overall survival versus standard therapies." In the analysis of CARTITUDE-4 data, 176 patients received CARVYKTI® as early as second line and 59 of those patients had standard-risk cytogenetics.1 At a median follow-up of 33.6 months, the 30-month PFS rate among the standard-risk patients in the as-treated population appeared to plateau at 80.5 percent (95 percent CI, 67.2–88.8) following a single infusion of CARVYKTI®.1 Notably, all 26 patients (100%) from this group who achieved minimal residual disease (MRD)-negative complete response at 12 months following CARVYKTI® infusion remained progression-free at 30 months.1 Additionally, a translational analysis evaluated the relationship between immune biomarkers and PFS in patients treated with CARVYKTI® in CARTITUDE-1 and CARTITUDE-4.2 Using CARVYKTI® after one or two prior lines of therapy demonstrated stronger immune fitness versus patients with three or more prior lines of therapy, characterized by increased baseline CD4⁺ naïve T cells (a type of immune cell that has not encountered an antigen) in peripheral blood.2 Bone marrow tumor analyses from patients treated with CARVYKTI® in CARTITUDE-4 also demonstrated a more immune-activated profile in patients treated after one prior line of therapy versus three.2 These biomarker data identify potential immunologic factors associated with longer PFS and support the improved survival outcomes exhibited with CARVYKTI® for patients treated as early as second line.2 As CARVYKTI® use has broadened across academic centers and community practices, Johnson & Johnson continues to collect and analyze clinical and real-world data to further characterize long-term remission outcomes and safety trends. This comprehensive experience across diverse patient populations provides an important foundation for expanding use into earlier treatment settings. About the CARTITUDE-1 Study CARTITUDE-1 (NCT03548207) is a Phase 1b/2, open-label, multicenter study that evaluated the efficacy and safety of cilta-cel in adults with relapsed and/or refractory multiple myeloma (RRMM), 99 percent of whom were refractory to the last line of treatment; 88 percent of whom were triple-class refractory, meaning their cancer did not or no longer responds to an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody.3 The primary objective of the Phase 1b portion of the study, involving 29 patients, was to characterize the safety and confirm the dose of cilta-cel, informed by the first-in-human study with LCAR-B38M CAR-T cells (LEGEND-2). Based on the safety profile observed in this portion of the study, outpatient dosing is being evaluated in additional CARTITUDE studies. The Phase 2 portion of the study is evaluating the efficacy of cilta-cel with overall response as the primary endpoint. The study involved patients with heavily pretreated RRMM who historically have an expected median PFS of <6 months and median overall survival of ~1 year. About the CARTITUDE-4 Study CARTITUDE-4 (NCT04181827) is the first randomized Phase 3 study evaluating the efficacy and safety of CARVYKTI®. The study compares CARVYKTI® with standard of care treatments PVd or DPd in adult patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy. The primary endpoint of the study is PFS; safety, OS, minimal residual disease negative rate and overall response rate are secondary endpoints. About CARVYKTI ® (ciltacabtagene autoleucel; cilta-cel) CARVYKTI® (cilta-cel) received U.S. Food and Drug Administration approval in February 2022 for the treatment of adults with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.4 In April 2024, CARVYKTI® was approved as the first and only cell therapy in the U.S. for treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor, an immunomodulatory agent, and who are refractory to lenalidomide. In April 2024, the European Medicines Agency (EMA) approved a Type II variation for CARVYKTI® for the treatment of adults with relapsed and refractory multiple myeloma who have received at least one prior therapy, including an immunomodulatory agent and a proteasome inhibitor, have demonstrated disease progression on the last therapy, and are refractory to lenalidomide. CARVYKTI® is a BCMA-directed, genetically modified autologous T-cell immunotherapy that involves reprogramming a patient's own T-cells with a transgene encoding chimeric antigen receptor (CAR) that directs the CAR-positive T cells to eliminate cells that express BCMA. BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B cells and plasma cells. The CARVYKTI® CAR protein features two BCMA-targeting single domains designed to confer high avidity against human BCMA. Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells. In December 2017, Janssen Biotech, Inc., a Johnson & Johnson company, entered into an exclusive worldwide license and collaboration agreement with Legend Biotech USA, Inc. to develop and commercialize CARVYKTI®. For more information, visit . About Multiple Myeloma Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.5 In multiple myeloma, these plasma cells proliferate and spread rapidly and replace normal cells in the bone marrow with tumors.6 Multiple myeloma is the third most common blood cancer worldwide and remains an incurable disease.7 In 2024, it was estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 people would die from the disease.8 People living with multiple myeloma have a 5-year survival rate of 59.8 percent.9 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels and kidney problems or infections.10,11 CARVYKTI® IMPORTANT SAFETY INFORMATION INDICATIONS AND USAGE CARVYKTI® (ciltacabtagene autoleucel) is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory multiple myeloma, who have received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Increased early mortality. In CARTITUDE-4, a (1:1) randomized controlled trial, there was a numerically higher percentage of early deaths in patients randomized to the CARVYKTI® treatment arm compared to the control arm. Among patients with deaths occurring within the first 10 months from randomization, a greater proportion (29/208; 14%) occurred in the CARVYKTI® arm compared to (25/211; 12%) in the control arm. Of the 29 deaths that occurred in the CARVYKTI® arm within the first 10 months of randomization, 10 deaths occurred prior to CARVYKTI® infusion, and 19 deaths occurred after CARVYKTI® infusion. Of the 10 deaths that occurred prior to CARVYKTI® infusion, all occurred due to disease progression, and none occurred due to adverse events. Of the 19 deaths that occurred after CARVYKTI® infusion, 3 occurred due to disease progression, and 16 occurred due to adverse events. The most common adverse events were due to infection (n=12). Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with CARVYKTI®. Among patients receiving CARVYKTI® for RRMM in the CARTITUDE-1 & -4 studies (N=285), CRS occurred in 84% (238/285), including ≥ Grade 3 CRS (ASTCT 2019) in 4% (11/285) of patients. Median time to onset of CRS, any grade, was 7 days (range: 1 to 23 days). CRS resolved in 82% with a median duration of 4 days (range: 1 to 97 days). The most common manifestations of CRS in all patients combined (≥10%) included fever (84%), hypotension (29%) and aspartate aminotransferase increased (11%). Serious events that may be associated with CRS include pyrexia, hemophagocytic lymphohistiocytosis, respiratory failure, disseminated intravascular coagulation, capillary leak syndrome, and supraventricular and ventricular tachycardia. CRS occurred in 78% of patients in CARTITUDE-4 (3% Grade 3 to 4) and in 95% of patients in CARTITUDE-1 (4% Grade 3 to 4). Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of HLH/MAS, and the physiology of the syndromes may overlap. HLH/MAS is a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS. Confirm that a minimum of 2 doses of tocilizumab are available prior to infusion of CARVYKTI®. Of the 285 patients who received CARVYKTI® in clinical trials, 53% (150/285) patients received tocilizumab; 35% (100/285) received a single dose, while 18% (50/285) received more than 1 dose of tocilizumab. Overall, 14% (39/285) of patients received at least 1 dose of corticosteroids for treatment of CRS. Monitor patients at least daily for 7 days following CARVYKTI® infusion for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 2 weeks after infusion. At the first sign of CRS, immediately institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. Neurologic toxicities, which may be severe, life-threatening, or fatal, occurred following treatment with CARVYKTI®. Neurologic toxicities included ICANS, neurologic toxicity with signs and symptoms of Parkinsonism, GBS, immune mediated myelitis, peripheral neuropathies, and cranial nerve palsies. Counsel patients on the signs and symptoms of these neurologic toxicities, and on the delayed nature of onset of some of these toxicities. Instruct patients to seek immediate medical attention for further assessment and management if signs or symptoms of any of these neurologic toxicities occur at any time. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies for RRMM, one or more neurologic toxicities occurred in 24% (69/285), including ≥ Grade 3 cases in 7% (19/285) of patients. Median time to onset was 10 days (range: 1 to 101) with 63/69 (91%) of cases developing by 30 days. Neurologic toxicities resolved in 72% (50/69) of patients with a median duration to resolution of 23 days (range: 1 to 544). Of patients developing neurotoxicity, 96% (66/69) also developed CRS. Subtypes of neurologic toxicities included ICANS in 13%, peripheral neuropathy in 7%, cranial nerve palsy in 7%, parkinsonism in 3%, and immune mediated myelitis in 0.4% of the patients. Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS): Patients receiving CARVYKTI® may experience fatal or life-threatening ICANS following treatment with CARVYKTI®, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. Among patients receiving CARVYKTI® in the CARTITUDE-1 & -4 studies, ICANS occurred in 13% (36/285), including Grade ≥3 in 2% (6/285) of the patients. Median time to onset of ICANS was 8 days (range: 1 to 28 days). ICANS resolved in 30 of 36 (83%) of patients, with a median time to resolution of 3 days (range: 1 to 143 days). Median duration of ICANS was 6 days (range: 1 to 1229 days) in all patients, including those with ongoing neurologic events at the time of death or data cutoff. Of patients with ICANS, 97% (35/36) had CRS. The onset of ICANS occurred during CRS in 69% of patients, before and after the onset of CRS in 14% of patients, respectively. Immune Effector Cell-associated Neurotoxicity Syndrome occurred in 7% of patients in CARTITUDE-4 (0.5% Grade 3) and in 23% of patients in CARTITUDE-1 (3% Grade 3). The most frequent (≥2%) manifestations of ICANS included encephalopathy (12%), aphasia (4%), headache (3%), motor dysfunction (3%), ataxia (2%), and sleep disorder (2%). Monitor patients at least daily for 7 days following CARVYKTI® infusion for signs and symptoms of ICANS. Rule out other causes of ICANS symptoms. Monitor patients for signs or symptoms of ICANS for at least 2 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed. Advise patients to avoid driving for at least 2 weeks following infusion. Parkinsonism: Neurologic toxicity with parkinsonism has been reported in clinical trials of CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & -4 studies, parkinsonism occurred in 3% (8/285), including Grade ≥3 in 2% (5/285) of the patients. Median time to onset of parkinsonism was 56 days (range: 14 to 914 days). Parkinsonism resolved in 1 of 8 (13%) of patients with a median time to resolution of 523 days. Median duration of parkinsonism was 243.5 days (range: 62 to 720 days) in all patients, including those with ongoing neurologic events at the time of death or data cutoff. The onset of parkinsonism occurred after CRS for all patients and after ICANS for 6 patients. Parkinsonism occurred in 1% of patients in CARTITUDE-4 (no Grade 3 to 4) and in 6% of patients in CARTITUDE-1 (4% Grade 3 to 4). Manifestations of parkinsonism included movement disorders, cognitive impairment, and personality changes. Monitor patients for signs and symptoms of parkinsonism that may be delayed in onset and managed with supportive care measures. There is limited efficacy information with medications used for the treatment of Parkinson's disease for the improvement or resolution of parkinsonism symptoms following CARVYKTI® treatment. Guillain-Barré syndrome: A fatal outcome following GBS occurred following treatment with CARVYKTI® despite treatment with intravenous immunoglobulins. Symptoms reported include those consistent with Miller-Fisher variant of GBS, encephalopathy, motor weakness, speech disturbances, and polyradiculoneuritis. Monitor for GBS. Evaluate patients presenting with peripheral neuropathy for GBS. Consider treatment of GBS with supportive care measures and in conjunction with immunoglobulins and plasma exchange, depending on severity of GBS. Immune mediated myelitis: Grade 3 myelitis occurred 25 days following treatment with CARVYKTI® in CARTITUDE-4 in a patient who received CARVYKTI® as subsequent therapy. Symptoms reported included hypoesthesia of the lower extremities and the lower abdomen with impaired sphincter control. Symptoms improved with the use of corticosteroids and intravenous immune globulin. Myelitis was ongoing at the time of death from other cause. Peripheral neuropathy occurred following treatment with CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & -4 studies, peripheral neuropathy occurred in 7% (21/285), including Grade ≥3 in 1% (3/285) of the patients. Median time to onset of peripheral neuropathy was 57 days (range: 1 to 914 days). Peripheral neuropathy resolved in 11 of 21 (52%) of patients with a median time to resolution of 58 days (range: 1 to 215 days). Median duration of peripheral neuropathy was 149.5 days (range: 1 to 692 days) in all patients including those with ongoing neurologic events at the time of death or data cutoff. Peripheral neuropathies occurred in 7% of patients in CARTITUDE-4 (0.5% Grade 3 to 4) and in 7% of patients in CARTITUDE-1 (2% Grade 3 to 4). Monitor patients for signs and symptoms of peripheral neuropathies. Patients who experience peripheral neuropathy may also experience cranial nerve palsies or GBS. Cranial nerve palsies occurred following treatment with CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & -4 studies, cranial nerve palsies occurred in 7% (19/285), including Grade ≥3 in 1% (1/285) of the patients. Median time to onset of cranial nerve palsies was 21 days (range: 17 to 101 days). Cranial nerve palsies resolved in 17 of 19 (89%) of patients with a median time to resolution of 66 days (range: 1 to 209 days). Median duration of cranial nerve palsies was 70 days (range: 1 to 262 days) in all patients, including those with ongoing neurologic events at the time of death or data cutoff. Cranial nerve palsies occurred in 9% of patients in CARTITUDE-4 (1% Grade 3 to 4) and in 3% of patients in CARTITUDE-1 (1% Grade 3 to 4). The most frequent cranial nerve affected was the 7th cranial nerve. Additionally, cranial nerves III, V, and VI have been reported to be affected. Monitor patients for signs and symptoms of cranial nerve palsies. Consider management with systemic corticosteroids, depending on the severity and progression of signs and symptoms. Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS): Among patients receiving CARVYKTI® in the CARTITUDE-1 & -4 studies, HLH/MAS occurred in 1% (3/285) of patients. All events of HLH/MAS had onset within 99 days of receiving CARVYKTI®, with a median onset of 10 days (range: 8 to 99 days), and all occurred in the setting of ongoing or worsening CRS. The manifestations of HLH/MAS included hyperferritinemia, hypotension, hypoxia with diffuse alveolar damage, coagulopathy and hemorrhage, cytopenia, and multi-organ dysfunction, including renal dysfunction and respiratory failure. Patients who develop HLH/MAS have an increased risk of severe bleeding. Monitor hematologic parameters in patients with HLH/MAS and transfuse per institutional guidelines. Fatal cases of HLH/MAS occurred following treatment with CARVYKTI®. HLH is a life-threatening condition with a high mortality rate if not recognized and treated early. Treatment of HLH/MAS should be administered per institutional standards. Prolonged and Recurrent Cytopenias: Patients may exhibit prolonged and recurrent cytopenias following lymphodepleting chemotherapy and CARVYKTI® infusion. Among patients receiving CARVYKTI® in the CARTITUDE-1 & -4 studies, Grade 3 or higher cytopenias not resolved by Day 30 following CARVYKTI® infusion occurred in 62% (176/285) of the patients and included thrombocytopenia 33% (94/285), neutropenia 27% (76/285), lymphopenia 24% (67/285), and anemia 2% (6/285). After Day 60 following CARVYKTI® infusion, 22%, 20%, 5%, and 6% of patients had a recurrence of Grade 3 or 4 lymphopenia, neutropenia, thrombocytopenia, and anemia, respectively, after initial recovery of their Grade 3 or 4 cytopenia. Seventy-seven percent (219/285) of patients had one, two, or three or more recurrences of Grade 3 or 4 cytopenias after initial recovery of Grade 3 or 4 cytopenia. Sixteen and 25 patients had Grade 3 or 4 neutropenia and thrombocytopenia, respectively, at the time of death. Monitor blood counts prior to and after CARVYKTI® infusion. Manage cytopenias with growth factors and blood product transfusion support according to local institutional guidelines. Infections: CARVYKTI® should not be administered to patients with active infection or inflammatory disorders. Severe, life-threatening, or fatal infections occurred in patients after CARVYKTI® infusion. Among patients receiving CARVYKTI® in the CARTITUDE-1 & -4 studies, infections occurred in 57% (163/285), including Grade ≥3 in 24% (69/285) of patients. Grade 3 or 4 infections with an unspecified pathogen occurred in 12%, viral infections in 6%, bacterial infections in 5%, and fungal infections in 1% of patients. Overall, 5% (13/285) of patients had Grade 5 infections, 2.5% of which were due to COVID-19. Patients treated with CARVYKTI® had an increased rate of fatal COVID-19 infections compared to the standard therapy arm. Monitor patients for signs and symptoms of infection before and after CARVYKTI® infusion and treat patients appropriately. Administer prophylactic, pre-emptive, and/or therapeutic antimicrobials according to the standard institutional guidelines. Febrile neutropenia was observed in 5% of patients after CARVYKTI® infusion and 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. Counsel patients on the importance of prevention measures. Follow institutional guidelines for the vaccination and management of immunocompromised patients with COVID-19. Viral Reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients with hypogammaglobulinemia. Perform screening for Cytomegalovirus (CMV), HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) or any other infectious agents if clinically indicated in accordance with clinical guidelines before collection of cells for manufacturing. Consider antiviral therapy to prevent viral reactivation per local institutional guidelines/clinical practice. Reactivation of John Cunningham (JC) virus, leading to progressive multifocal leukoencephalopathy (PML), including cases with fatal outcomes, have been reported following treatment. Perform appropriate diagnostic evaluations in patients with neurological adverse events. Hypogammaglobulinemia can occur in patients receiving treatment with CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & -4 studies, hypogammaglobulinemia adverse event was reported in 36% (102/285) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 93% (265/285) of patients. Hypogammaglobulinemia either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion occurred in 94% (267/285) of patients treated. Fifty-six percent (161/285) of patients received intravenous immunoglobulin (IVIG) post CARVYKTI® for either an adverse reaction or prophylaxis. Monitor immunoglobulin levels after treatment with CARVYKTI® and administer IVIG for IgG <400 mg/dL. Manage per local institutional guidelines, including infection precautions and antibiotic or antiviral prophylaxis. Use of Live Vaccines: The safety of immunization with live viral vaccines during or following CARVYKTI® 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 CARVYKTI® treatment, and until immune recovery following treatment with CARVYKTI®. Hypersensitivity Reactions occurred following treatment with CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & -4 studies, hypersensitivity reactions occurred in 5% (13/285), all of which were ≤2 Grade. Manifestations of hypersensitivity reactions included flushing, chest discomfort, tachycardia, wheezing, tremor, burning sensation, non-cardiac chest pain, and pyrexia. Serious hypersensitivity reactions, including anaphylaxis, may be due to the dimethyl sulfoxide (DMSO) in CARVYKTI®. Patients should be carefully monitored for 2 hours after infusion for signs and symptoms of severe reaction. Treat promptly and manage patients appropriately according to the severity of the hypersensitivity reaction. Immune effector cell-associated enterocolitis (IEC-EC) has occurred in patients treated with CARVYKTI®. Manifestations include severe or prolonged diarrhea, abdominal pain, and weight loss requiring parenteral nutrition. IEC-EC has been associated with fatal outcome from perforation or sepsis. Manage according to institutional guidelines, including referral to gastroenterology and infectious disease specialists. In cases of refractory IEC-EC, consider additional workup to exclude alternative etiologies, including T-cell lymphoma of the GI tract, which has been reported in the post marketing setting. Secondary Malignancies: Patients treated with CARVYKTI® may develop secondary malignancies. Among patients receiving CARVYKTI® in the CARTITUDE-1 & -4 studies, myeloid neoplasms occurred in 5% (13/285) of patients (9 cases of myelodysplastic syndrome, 3 cases of acute myeloid leukemia, and 1 case of myelodysplastic syndrome followed by acute myeloid leukemia). The median time to onset of myeloid neoplasms was 447 days (range: 56 to 870 days) after treatment with CARVYKTI®. Ten of these 13 patients died following the development of myeloid neoplasms; 2 of the 13 cases of myeloid neoplasm occurred after initiation of subsequent antimyeloma therapy. Cases of myelodysplastic syndrome and acute myeloid leukemia have also been reported in the post marketing setting. T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including CARVYKTI®. Mature T-cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusions, and may include fatal outcomes. Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Janssen Biotech, Inc., at 1-800-526-7736 for reporting and to obtain instructions on collection of patient samples. ADVERSE REACTIONS The most common nonlaboratory adverse reactions (incidence greater than 20%) are pyrexia, cytokine release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections-pathogen unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting. The most common Grade 3 or 4 laboratory adverse reactions (incidence greater than or equal to 50%) include lymphopenia, neutropenia, white blood cell decreased, thrombocytopenia, and anemia. Please read full Prescribing Information, including Boxed Warning, for CARVYKTI®. About Johnson & Johnson At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at or at . Follow us at @JNJInnovMed. Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of CARVYKTI®. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's most recent Annual Report on Form 10-K, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at , or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments. Footnotes: * Luciano J. Costa, M.D., Ph.D., Professor of Medicine at the University of Alabama, has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work. 1 Dr. Parekh S, et al. Earlier use of ciltacabtagene autoleucel (cilta-cel) is associated with better immune fitness and stronger immune effects as shown by correlative analysis of peripheral blood and the bone marrow tumor microenvironment (TME) from the CARTITUDE-4 study. American Society of Hematology 2025 Annual Meeting. Accessed December 2025. 2 Dr. Costa L, et al. Long-term progression-free survival benefit with ciltacabtagene autoleucel in standard-risk relapsed/refractory multiple myeloma. American Society of Hematology 2025 Annual Meeting. Accessed December 2025. 3 Usmani S. Phase 1b/2 study of ciltacabtagene autoleucel, a BCMA-directed CAR-T cell therapy, in patients with relapsed/refractory multiple myeloma (CARTITUDE-1): Two years post-LPI. Abstract #8028 [Poster]. Presented at the 2022 American Society of Clinical Oncology Annual Meeting. 4 CARVYKTI® U.S. Prescribing Information. 5 Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol. 2020;95(5):548-5672020;95(5):548-567. 6 National Cancer Institute. Plasma Cell Neoplasms. . Accessed December 2025. 7 City of Hope. Multiple Myeloma: Causes, Symptoms & Treatments. . Accessed December 2025. 8 American Cancer Society. Key Statistics About Multiple Myeloma. . Accessed December 2025. 9 SEER Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. . Accessed December 2025. 10 American Cancer Society. What is Multiple Myeloma? . Accessed December 2025. 11 American Cancer Society. Multiple Myeloma Early Detection, Diagnosis, and Staging . Accessed December 2025. SOURCE Johnson & Johnson 21% more press release views with Request a Demo