Immune Globulin Intravenous (Human) (Octapharma)

神经肌肉疾病文献速递（第11期） 本期覆盖：2026年09月21日—2026年09月27日 PubMed 新发表文献 本周共精选 26 篇：重症肌无力 8 篇｜肌萎缩侧索硬化 10 篇｜其他神经肌肉疾病 8 篇（多种酰基辅酶A脱氢酶缺乏症本周无新文献，按规则跳过该章节）一、重症肌无力（Myasthenia Gravis）AChR 阻断抗体的纵向动态：与重症肌无力严重程度相关并预示眼肌型全身化 Longitudinal dynamics and clinical significance of acetylcholine receptor blocking antibodies in myasthenia gravis（Vakrakou AG, Belimezi M, Strataki E, et al.，Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology，2026-09-25） AChR 结合抗体是 MG 诊断的常规指标，但针对同一受体离子通道的「阻断抗体」的纵向临床意义尚不明确。这项前瞻性研究纳入 47 例 AChR 抗体阳性 MG 患者，平均随访 2.8 年，累计 121 次系列抗体检测；结合抗体用常规放射免疫沉淀法测定，阻断活性用竞争性放射免疫法测定，严重程度按 MGFA 分级评估，纵向关联采用广义估计方程（GEE）分析。结果显示，阻断抗体（抑制率 >20%）与跨随访时点的 MGFA 严重程度相关（β=0.045，p<0.001），而结合抗体水平与严重程度无显著关联。眼肌型亚组的发现更为直观：13 例眼肌型起病患者中，8 例进展为全身型者阻断抗体全部阳性，而 5 例始终停留于眼肌型者全部阴性；全身型 MG 患者中阻断抗体阳性率达 90.5%。作者认为，AChR 阻断抗体随时间与病情严重程度相关，并可能有助于识别有全身化风险的眼肌型 MG 患者，提示其有潜力进入临床抗体检测组合，用于预后分层与随访监测。 备注：结合抗体：多个结合抗体能同时附着在相邻的AChR上，它们的Fc段密集排列，从而高效激活补体，破坏神经肌肉接头。阻断抗体：它的主要功能是物理性地占据AChR上本该由乙酰胆碱结合的位点，直接阻断神经信号。这种“占位”方式通常不涉及Fc段的密集聚集，因此激活补体的能力很弱或根本不激活。美国真实世界研究：依库珠单抗/雷夫利珠单抗治疗患者的脑膜炎奈瑟菌感染率持续低位 Meningococcal infection in patients receiving eculizumab or ravulizumab for generalized myasthenia gravis or neuromyelitis optica spectrum disorder: A real-world study of US clinical practice（Pandya S, Jha L, Akpoji U, et al.，Journal of the neurological sciences，2026-09-21） 依库珠单抗与雷夫利珠单抗是已获批用于全身型 MG（gMG）和视神经脊髓炎谱系疾病（NMOSD）等适应证的补体终末抑制剂，但阻断终末补体理论上会增加奈瑟菌易感性，用药前的疫苗接种与风险评估因此备受关注。本研究基于 Alexion 安全数据库的上市后药物警戒数据（依库珠单抗数据截至 2025 年 10 月 1 日、雷夫利珠单抗截至 2025 年 12 月 31 日），评估美国用药人群累积暴露校正后的脑膜炎奈瑟菌（Nm）感染率与死亡率。截至 2025 年，两药在美国的累积暴露分别达 34,713 与 21,348 患者年；Nm 累积感染率分别为 0.15 和 0.08/100 患者年，累积死亡率均为 0.01/100 患者年，且随暴露量增加保持稳定。分适应证看，gMG 患者的 Nm 感染率（依库珠单抗 0.05、雷夫利珠单抗 0.03/100 患者年）低于 NMOSD（0.12、0.13/100 患者年），且两药治疗的 gMG 与 NMOSD 患者均无 Nm 相关死亡报告。作者结论：在暴露量持续增加的背景下，Nm 感染及相关死亡率仍稳定处于低位，提示现有风险防控策略（含疫苗接种）有效，为补体抑制剂在 gMG 中的长期安全使用提供了真实世界依据。匹配调整间接比较：Zilucoplan 对比 IVIG、依库珠单抗与雷夫利珠单抗治疗全身型重症肌无力 Comparative Efficacy of Zilucoplan Versus Intravenous Immunoglobulin, Eculizumab, and Ravulizumab Using Matching-Adjusted Indirect Comparisons（Betts A, Jacob S, Chakravarty A, et al.，Neurology and therapy，2026-09-24） Zilucoplan 是皮下自行注射的补体 C5 抑制剂，已获批用于 AChR 抗体阳性 gMG，但目前缺乏与 IVIG、依库珠单抗、雷夫利珠单抗的头对头比较。本研究采用匹配调整间接比较（MAIC），通过倾向评分加权平衡 III 期试验人群的基线协变量，对 zilucoplan 与三种疗法进行疗效比较。结果显示：与 IVIG 相比，zilucoplan 治疗 2 周时 QMG 评分差异为 -1.95（95% CI -3.50～-0.39）、4 周时为 -3.30（-4.89～-1.71），均有利于 zilucoplan；在难治性 gMG 中，与依库珠单抗 24/26 周比较，zilucoplan 在 MG-ADL（-1.99，-3.30～-0.69）、QMG（-3.23，-4.63～-1.82）和 MGC（-4.27，-6.79～-1.76）上均显示统计学显著优势；与雷夫利珠单抗 24/26 周比较，zilucoplan 在 MG-ADL（-2.70，-3.74～-1.67）与 QMG（-5.72，-7.02～-4.43）上同样占优。需要提醒的是，MAIC 依赖跨试验人群匹配、存在方法学局限，结果应视为探索性证据。作者认为，在无头对头数据的情况下，这些分析可为 gMG 的治疗决策提供补充参考。匹配调整间接比较：Rozanolixizumab 对比艾加莫德或 IVIG 治疗全身型重症肌无力 Comparative Efficacy of Rozanolixizumab with Efgartigimod or Intravenous Immunoglobulin in Generalized Myasthenia Gravis Using Matching Adjusted Indirect Comparisons（Maheshwari V, Barnett Tapia C, Chakravarty A, et al.，Neurology and therapy，2026-09-24） Rozanolixizumab 是皮下给药的 FcRn 拮抗剂，与另一种 FcRn 拮抗剂艾加莫德及经典疗法 IVIG 之间同样缺乏头对头证据。本研究采用 MAIC 比较其 7 mg/kg 与 10 mg/kg 两个剂量方案与艾加莫德 10 mg/kg IV（锚定比较）及 IVIG（非锚定比较）的疗效，用倾向评分加权平衡试验人群。结果显示：rozanolixizumab 与艾加莫德总体疗效相当，仅第 6 周时 10 mg/kg 剂量在 QMG（均差 -2.80，95% CI -5.00～-0.60）与 MGC（-3.89，-6.72～-1.05）上显著优于艾加莫德；与 IVIG 相比，两个剂量的 rozanolixizumab 在 2 周（7 mg/kg：-1.95，-3.79～-0.11；10 mg/kg：-1.99，-3.71～-0.26）与 4 周（-3.40，-5.23～-1.56；-3.99，-5.81～-2.17）的 QMG 较基线改善均显著更大，但 2 周时的 QMG 应答率差异无统计学意义。作者结论：FcRn 抑制剂是 gMG 重要的靶向治疗选择；在缺乏直接比较证据时，MAIC 可为个体化选药提供间接参考，但解读时需牢记其非随机比较的本质。方案分层的贝叶斯模型化 Meta 分析：九种靶向生物制剂治疗全身型重症肌无力的疗效比较与机制类别差异 Regimen-stratified Bayesian model-based meta-analysis of targeted biologics in generalised myasthenia gravis: efficacy comparison, mechanism-level class contrast, and endpoint sensitivity with model-informed trial design（Roy SS, Padhy BM, Anil A, et al.，Naunyn-Schmiedeberg's archives of pharmacology，2026-09-22） 已有九种靶向生物制剂（覆盖四种作用机制）进入 gMG 的 III 期开发，但现有跨项目比较既未考虑持续给药与周期给药模式的差异，也未同时整合患者报告（MG-ADL）与医生评估（QMG）两类终点。本研究开展方案分层的贝叶斯模型化 Meta 分析（MBMA，PROSPERO 注册号 CRD420261288549），从九项安慰剂对照 III 期试验提取 MG-ADL 与 QMG 纵向数据，拟合六个层级非线性 Emax 模型。结果：MG-ADL 上 zilucoplan 最大效应最高（Emax 4.8 分，95% CrI 4.2-5.4），较安慰剂净获益 2.5（2.0-3.1）；QMG 上巴托克利单抗（batoclimab）居首（Emax 5.9，4.4-9.5；净获益 4.1，2.7-7.7）；艾加莫德在两量表上起效最快（≤1.6 周）。机制类别层面出现「量表依赖」的分化：FcRn 抑制剂在客观运动量表 QMG 上显著优于补体抑制剂（平均 Emax 5.28 vs 3.99，后验概率 99.7%），而在 MG-ADL 上两类无差异（后验概率 52.5%）；在整合疗效、安全性、耐受性与便利性的治疗选择框架中，batoclimab 在全部八个临床优先画像中排名最高。作者指出，这为机制导向的个体化治疗与终点优化提供了药效学依据，但 Emax/MBMA 属模型推断而非头对头结论，临床落地仍需谨慎。艾加莫德个体化间隔给药维持轻微症状状态：单臂开放标签临床试验方案 Maintenance of Minimal Manifestation Status with Individualized-Interval Efgartigimod in Generalized Myasthenia Gravis: Study Protocol for a Single-Arm, Open-Label Clinical Trial（Suzuki T, Fujimaki M, Igari K, et al.，Neurology and therapy，2026-09-24） 艾加莫德（efgartigimod）是 FcRn 拮抗剂，注册试验采用固定的「4 周给药+4 周停药」周期，但临床上如何以最低治疗强度长期维持「轻微表现（MM）」状态尚不清楚。这项单臂、开放标签、单中心探索性研究（日本临床试验注册号 jRCTs031260127）计划纳入 24 例 18～80 岁 gMG 患者，入组要求为在既往试验或常规治疗中经艾加莫德（静脉制剂或皮下制剂）联合泼尼松龙 ≤5 mg/天达到 MM（MG-ADL ≤2 或 MG 复合评分 ≤4，常合并钙调磷酸酶抑制剂）。给药为每周期连续 4 周每周一次，周期间隔依据最差周 MG-ADL 评分个体化调整：病情恶化则缩短 1 周，连续两个周期稳定则延长 1 周；激素与背景免疫抑制剂保持不变，治疗最长 55 周。主要终点为观察期内按预设周期标准持续维持 MM 且泼尼松龙 ≤5 mg/天的患者比例；次要终点包括 MG-ADL、MGC、QMG、MG-QOL15r-J 评分变化、患者报告的治疗便利性、血清 IgG 变化、周期间隔分布、自身抗体滴度及安全性。该方案直指 gMG 长期管理中「降阶梯个体化」这一现实问题，其结果值得随访。rs28362336 被鉴定为全身型重症肌无力风险 SNP：通过增强子调控 HCG27 表达 Identification of rs28362336 as a risk SNP for generalized myasthenia gravis and its impact on HCG27 regulation（Chen Z, Guo Q, Tian L, et al.，PloS one，2026-09-23） MG 具有遗传易感性，全基因组关联研究（GWAS）已定位多个风险位点，但长链非编码 RNA（lncRNA）相关 SNP 的研究仍然很少。本研究先用 MG GWAS 数据筛查调控区 SNP，再开展 161 例患者对 161 例对照的病例对照研究（SNaPshot 分型），结合 LASSO 回归与随机森林筛选风险因素，并通过 eQTL、ChIP-PCR、qRT-PCR 与荧光原位杂交等实验解析 rs28362336 的功能机制。结果显示，显著 SNP 位于第 1、6、11、17、18 号染色体；总体病例与对照间基因型及等位基因频率无差异，但亚型分析发现 HCG27 rs9263872（TT）、rs9263875（GG）与 rs28362336（GG）基因型与全身型 MG（gMG）风险相关，rs9263875 G 等位基因关联 gMG，HCG9 rs3823381 T 等位基因关联眼肌型；机器学习进一步将 rs28362336 列为 MG 风险因素。功能层面，H3K4me1、H3K27ac 与 RNA 聚合酶 II 在 rs28362336 位点富集，提示其位于 HCG27 上游并具增强子活性；MG 患者（尤其携带 rs28362336 GG 基因型的 gMG）HCG27 表达升高，且 HCG27 能促进 CD4+ T 细胞增殖并抑制其凋亡。研究提示 HCG27 相关 SNP 与 gMG 易感性相关，HCG27 可能通过调节 CD4+ T 细胞参与 MG 发病。微创胸腺切除术的入路比较：叙述性综述 Minimally Invasive Approaches for Thymectomy: A Narrative Review and Comparison of Surgical Approaches（Wheelwright M, Krantz SB，The Annals of thoracic surgery，2026-09-23） 胸腺切除术是 MG（尤其合并胸腺瘤者）的重要治疗手段，微创入路近年来快速演化，但各术式如何选择缺乏系统梳理。这篇叙述性综述基于 PubMed/MEDLINE 检索并结合资深作者的临床经验，比较了左侧与右侧胸腔镜/机器人入路、剑突下入路及单孔机器人剑突下入路等的适应证、技术要点与风险获益。总体而言，无论采用哪种具体技术，微创入路较开放手术均安全有效，住院时间更短、镇痛更好、恢复工作更早。具体到入路选择：左侧入路可能较右侧带来额外获益，对重症肌无力尤其如此；剑突下入路对双侧胸腺及膈角的显露可能优于经侧胸壁入路；单孔机器人剑突下入路前景可观，但仍处于应用早期。作者认为，微创胸腺切除的适用范围仍在扩大，可切除的肿瘤更大、切除更复杂，技术进步将持续改善各类患者的结局。对参与 MG 多学科诊疗的神经科医生而言，这篇综述有助于理解外科入路选择的现实考量。三、肌萎缩侧索硬化（Amyotrophic Lateral Sclerosis）中国 441 例延髓起病运动神经元病的自然史：单中心回顾性研究 Natural history of 441 cases of bulbar onset motor neuron disease (MND) in China: a single-center retrospective study（Ding J, Hu N, Tian H, et al.，Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology，2026-09-24） 延髓起病的运动神经元病（MND）通常预后较差，但大样本自然史与预后因素数据在国内仍有限。这项单中心回顾性研究纳入 2014 年 1 月至 2023 年 12 月间规律随访的 441 例延髓起病 MND 患者，回顾初诊临床特征、从起病区域进展至下一区域的时间以及死亡或气管切开时间，采用 Kaplan-Meier 与 Cox 回归分析。结果显示：病情进展最常从延髓扩展至上肢（77.1%），其次为下肢（16.4%）与呼吸肌（6.5%），中位间隔 6.0（1.0-48.0）个月；215 例患者死亡或接受气管切开，中位生存时间为 43.0 个月（95% CI 39.1-46.9），1、2、3、4、5 年生存率分别为 96.6%、79.9%、59.1%、42.2% 和 29.9%。预后较好的相关因素包括：起病年龄更轻、ALSFRS-R 下降速度更慢、诊断延迟更长、进展至下一区域的时间更长，以及初诊时延髓区域仅有上运动神经元受累；第二受累区域为上肢者的结局优于呼吸肌受累者。作者指出，延髓起病 ALS 的自然史存在显著异质性，「纯上运动神经元型起病且随后累及上肢」的患者预后倾向良好，这为临床咨询与随访分层提供了量化依据。跨基因型汇聚的 TBK1 功能缺失驱动 gasdermin E 依赖性焦亡与运动神经元变性 Convergent TBK1 loss of function drives gasdermin E dependent pyroptosis and motor neuron degeneration across ALS genotypes（Qi Z, Liu X, Geng L, et al.，Cell death and differentiation，2026-09-21） 不同遗传背景的 ALS 是否汇聚于共同致病通路尚不明确。本研究对 8 例家族性 ALS 患者进行全外显子测序，其中 3 例分别携带 TBK1（R573H）、TDP-43（G298V）/GARS（I44M）/SETX（L1304W）或 SOD1（G94R）/SQSTM1（G262R）致病变异。患者 iPSC 分化的运动神经元虽然携带不同突变，却一致表现为轴突与神经突缩短、TBK1 活性降低、磷酸化 TDP-43 增加伴胞质聚集，以及焦亡执行蛋白 gasdermin E（GSDME）与 caspase-8/7 的共组装；神经炎症刺激进一步促进 caspase-8/7 与 GSDME 切割、增加 RIPK1 磷酸化并抑制 TBK1 活化，在 SH-SY5Y 细胞中敲低 TBK1 可复现上述表型。研究者还构建了人源化 TBK1 R573H 敲入小鼠，小鼠出现进行性运动障碍、脊髓运动神经元丢失、神经炎症与 TDP-43 病理；LPS 攻击后易损神经元中 GSDME 与 caspase-7 切割增加、p-TDP-43 显著上调。研究将 TBK1 功能缺失定位为 caspase-8/7-GSDME 焦亡程序的上游驱动因素，在神经炎症、TDP-43 蛋白病与神经变性之间架起机制桥梁，提示 TBK1-caspase-GSDME 轴有望成为跨基因型 ALS 的疾病修饰治疗靶点。同源同一性分析破解外显率减低之谜，推进 ALS/FTD 基因发现 Identity-by-descent to resolve reduced penetrance and advance gene discovery in neurodegenerative disease（Henden L, Chan Moi Fat S, Smith A, et al.，Brain : a journal of neurology，2026-09-25） 在 ALS 和额颞叶痴呆（FTD）等晚发性神经退行性疾病中，外显率不全、遗传异质性与家族史缺失常使「家族性/散发性」的二分法失真，既拖慢基因发现，也影响临床风险评估。本研究在覆盖 ALS-FTD 疾病谱、共 3,524 名欧洲裔个体的跨大洲整合队列中开展全基因组同源同一性（IBD）推断，以发现隐匿亲缘关系并重建扩展家系。结果显示：IBD 共识别 793 对 1～6 度亲缘关系（从同胞到远房表亲），其中 31.5% 此前未被识别，15.8% 的配对双方临床诊断并不相同；在登记为「散发性」的个体中，5.5% 的 ALS 患者和 15.9% 的 FTD 患者与队列中另一名患者存在遗传亲缘，说明外显率减低掩盖了相当比例的可遗传疾病。携带已知 ALS/FTD 相关变异者男女性别比均衡（无论报告家族史或 IBD 推断亲缘如何），而不携带已知变异者仍呈男性优势，提示两类人群遗传背景不同。IBD 分析还发现 SOD1、C9orf72 等已知 ALS 基因的跨大洲奠基者网络，并从表面无关的家系中新建 73 个 IBD 定义的扩展家系；在候选位点 13q21.33 内，经多点连锁分析支持锁定三个共享罕见变异。作者认为，IBD 分析为晚发性神经退行性疾病的基因发现、外显率解析与遗传咨询提供了实用框架。 备注：对于外显不全的疾病，阴性家族史（家里没听说有其他人得病）往往不可靠，不能用来排除遗传病因。突触体整合多组学揭示 C9ORF72-额颞叶痴呆的突触组织紊乱与隐秘转录本突触定位 Integrative synaptosome multi-omics reveals disrupted synapse organization and localized cryptic transcripts in C9ORF72-frontotemporal dementia（Spillman AM, Alsop EB, Gittings LM, et al.，Acta neuropathologica，2026-09-25） C9ORF72 六核苷酸重复扩增（HRE）是 ALS 与 FTD 最常见的遗传病因，突触功能障碍与 TDP-43 病理是其共同特征，但突触层面的致病机制仍不清楚。本研究对 C9-FTD 患者死后额叶皮层来源的突触体及患者 iPSC 分化皮层神经元进行整合多组学分析：突触体蛋白质组识别出 1,324 个差异丰度蛋白（p<0.05），富集于突触囊泡运输与突触组织调控通路；突触体转录组发现 2,835 个差异表达的蛋白编码基因。C9-FTD iPSC 皮层神经元表现为兴奋性与抑制性突触后标志物减少，伴进行性神经网络活动受损，支持结构与功能双重缺陷；iPSC 突触体复现了患者脑组织中的关键分子通路，提示突触信号通路的汇聚性失调。蛋白与 RNA 层面的改变存在明显「解离」，符合病变突触中 RNA-蛋白丰度调控紊乱。与 TDP-43 功能缺失病理一致，研究在 C9-FTD 皮层突触体中检出含隐秘外显子（CE）的转录本（如 KALRN、STMN2），证明异常剪接的 RNA 可定位于突触区室——这是 TDP-43 蛋白病此前未被认识的特征。该研究为 C9 突触易损性提供了跨模型汇聚的分子通路图谱，也把 TDP-43 功能缺失的效应范围进一步推进到突触末端。线粒体靶向化合物 MA-5 通过增强线粒体功能改善 ALS 表型 Mitochonic acid 5 alleviates amyotrophic lateral sclerosis phenotypes via mitochondrial augmentation（Oikawa Y, Luo Y, Suzuki N, et al.，JCI insight，2026-09-22） 线粒体功能障碍是 ALS 的核心病理环节之一，但目前缺乏直接靶向线粒体的治疗手段。这项临床前研究评估了线粒体靶向化合物 mitochonic acid 5（MA-5）在多个 ALS 模型中的疗效：在表达突变人 SOD1（G85R）的果蝇模型中，MA-5 显著改善运动能力，并呈现线粒体完整性恢复趋势；在 ALS 患者皮肤成纤维细胞和 iPSC 分化运动神经元中，MA-5 恢复 ATP 产生并增加线粒体运动性。多组学分析提示 MA-5 调控线粒体相关基因表达并下调磷酸甘油穿梭，与线粒体活性氧产生的变化相关；转录组分析鉴定出 C7orf31 可作为监测 MA-5 疗效及 ALS 亚型诊断的潜在生物标志物。作者认为，MA-5 是有前景的 ALS 候选治疗药物，C7orf31 有望用于疗效监测与疾病分型。需要强调的是，该研究仍处于临床前阶段，果蝇、成纤维细胞与 iPSC 运动神经元中的获益能否转化到患者身上有待临床验证。ALS 患者步态特征与跌倒风险：12 个月前瞻性队列研究 Gait Characteristics and Fall Risk in Amyotrophic Lateral Sclerosis: A 12-Month Prospective Cohort Study（Hu N, Su N, Zhang D, et al.，Neuro-degenerative diseases，2026-09-22） ALS 患者跌倒常见且危害大，但将定量步态参数与跌倒结局关联的前瞻性数据一直稀缺。这项单中心前瞻性队列研究纳入 256 例 ALS 患者与 256 名匹配健康对照，基线采用三维视觉步态分析系统采集 19 项时空步态参数，随访 12 个月记录跌倒事件、轮椅使用时间与 ALSFRS-R 下降，并用多变量 logistic 回归筛选独立预测因素。结果显示：224 例可评估患者中 129 例（57.6%）在随访期间至少跌倒一次；起立-行走计时（TUG）时间延长（每秒 OR 1.083，95% CI 1.036-1.133，p<0.001）、更年轻（每年 OR 0.968，0.940-0.996，p=0.024）与 MRC 总分更低（每分 OR 0.976，0.954-0.998，p=0.035）是跌倒的独立预测因素，但模型区分度仅为中等（AUC 0.665，0.594-0.736）。步态速度（rs=0.366）与 TUG 时间（rs=-0.381）与轮椅使用时间的相关性最强（均 p<0.001），而所有步态参数均与 ALSFRS-R 下降速率无显著相关。作者指出，跌倒是多因素事件，TUG 时间、年龄与肌力可作初步筛查但预测精度有限；步态速度与 TUG 时间有望成为功能衰退的候选替代标志物，未来需结合认知评估、连续监测与社会心理因素提升预测能力。NRS2002 与 MNA-SF 在成人 ALS 营养状况与预后评估中的应用价值 [Evaluation value of NRS2002 and MNA-SF on nutritional status and prognosis in adult patients with amyotrophic lateral sclerosis]（Liu YW, Fan DS, Chen L，Zhonghua yi xue za zhi，2026-Sep-22） 营养不良是 ALS 中可干预的预后因素，但 NRS2002 与 MNA-SF 两个营养量表在 ALS 人群的一致性及其与疾病进展的关联尚待评估。这项前瞻性研究纳入北京大学第三医院 2024 年 1-12 月就诊的 148 例成人 ALS 患者（男 96、女 52，年龄中位数 56.0 岁），基线以 NRS2002 与 MNA-SF 进行营养评估，此后每 3 个月随访共 1 年，记录 ALSFRS-R、体重指数（BMI）与量表评分，计算 ALSFRS-R 下降速率（δFS）与 BMI 下降速率（δBMI），主要终点为死亡或气管切开。结果：按 NRS2002 判定营养不良风险组 45 例、正常组 99 例；按 MNA-SF 判定为 59 例对 89 例；两量表评估一致性良好。两量表评分均与 BMI、体重、前白蛋白、肌酐及甘油三酯等传统营养指标显著相关（如 MNA-SF 与 BMI 的 r=0.573，p<0.001）。线性混合效应模型（校正混杂因素）显示：NRS2002 评分越高，δFS（β=0.127，95% CI 0.065-0.189，p<0.001）与 δBMI（β=0.150，0.104-0.197）增加越快，为风险因素；MNA-SF 评分越高，δFS（β=-0.090，-0.116～-0.064，p<0.001）与 δBMI（β=-0.092，-0.113～-0.071）增加越慢，为保护因素。结论：NRS2002 与 MNA-SF 在 ALS 营养风险筛查中一致性好，其评分与功能衰退及体重变化速率相关，可作为 ALS 随访营养管理的实用工具。FUS-ALS 的线粒体、RNA 加工与应激反应失调：多数据集转录组学整合分析 Dysregulation of mitochondrial bioenergetics, RNA processing, and cellular stress responses in FUS-ALS: a multi-dataset transcriptomic perspective（Walden F, Reihani Y, Peters A, et al.，Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology，2026-09-24） FUS 基因突变（尤其侵袭性 P525L 变异）导致 FUS 蛋白核定位障碍、胞质异常聚集并改变 RNA 代谢，是家族性 ALS 的代表病因之一；星形胶质细胞亦通过非细胞自主机制参与疾病进展。本研究整合分析 5 个公开 RNA 测序数据集（携带 FUS 突变的 hiPSC 运动神经元与星形胶质细胞），通过差异表达与基因本体（GO）富集分析，寻找共享及细胞类型特异的分子机制。结果：两类细胞均出现线粒体/生物能通路（氧化磷酸化、ATP 代谢、翻译、膜电位）的汇聚性失调；运动神经元数据集中富集细胞周期调控、胞内转运与刺激应答等相对特异的通路，而两细胞类型仅共享少数通路，其中 NADH 脱氢酶复合体组装在所有数据集与两类细胞中均显著富集——线粒体复合物 I 是最强的汇聚信号；RNA 加工/剪接通路同样富集，与 FUS 的 RNA 结合功能一致。共享差异基因包括 COMT、TXNRD2、PCDHGB4 上调及 PCDH17、C11orf87 下调，涉及神经递质代谢、抗氧化防御与细胞黏附；氧化应激、自噬、热休克与内质网应激/UPR 通路广泛改变，UPR 基因以上调为主而炎症基因下调。作者结论：FUS-ALS 的核心是共享的线粒体复合物 I 与应激反应紊乱，叠加运动神经元固有的细胞周期与转运调控异常，体现汇聚性与细胞类型特异机制的交织。ALS 全病程中细胞死亡通路的治疗学意义 Therapeutic Implications of Cell Death Pathways Across the Course of Amyotrophic Lateral Sclerosis（Yu J, Xie D, Zeng X, et al.，Current neuropharmacology，2026-09-23） 凋亡、坏死性凋亡、铁死亡、焦亡、溶酶体细胞死亡、自噬依赖性细胞死亡、NETosis 等多种调节性细胞死亡通路均被报道参与 ALS，但各通路间的相互作用与相对贡献仍不清楚，这一知识缺口阻碍了有效疗法开发。本综述系统梳理了这些细胞死亡通路在 ALS 中的作用，并引入 M1-M4 分级框架，依据与人类疾病的相关性对来自人体尸检组织、患者来源细胞与动物模型的证据进行分级排序，同时讨论通路间串扰。作者提出一个重要假设：特定细胞死亡通路的相对贡献可能随疾病进展而动态变化，并将该假设与 King's 临床分期系统对应，构建「分期-通路」概念模型——作者明确说明这是用于生成假设的概念框架，而非已验证的临床算法，旨在区分既有疗法与临床前/探索性策略。未来研究应优先发展更贴近人类的模型系统、鉴定细胞死亡的纵向生物标志物，并开展严谨设计的联合治疗试验，最终实现按疾病分期选择针对性靶向细胞死亡通路的个体化策略。对关注铁死亡、焦亡等新型死亡通路的读者，本文提供了一个按人类证据强度分级的入门式地图。ALS 舌运动功能的表型相关特征：静态与动态声学指标比较 Phenotype-Related Characteristics of Tongue Motor Function in Amyotrophic Lateral Sclerosis: A Retrospective Comparative Study of Static and Dynamic Acoustic Measures（Tsujisawa Y, Takahashi-Iwata I, Yabe I, et al.，Folia phoniatrica et logopaedica : official organ of the International Association of Logopedics and Phoniatrics (IALP)，2026-09-22） 延髓功能评估对 ALS 患者的言语障碍管理至关重要，但静态与动态声学指标是否反映同一舌运动控制维度尚不清楚。这项回顾性研究纳入 68 例 ALS 患者（男 42、女 26），主要分析男性 42 例，按表型分为脊柱起病（21 例）、脊柱起病伴延髓受累（9 例）与延髓起病（12 例）三组；从持续元音 /a/、/o/ 提取静态指标（元音三角区面积 tVSA 与共振峰集中比率 FCR），从朗读句子中双元音 /ai/ 提取 F2 过渡时长与 F2 幅度等动态指标。结果显示：静态指标仅在与脊柱起病组中与 F2 幅度相关（r=0.458，p=0.049），其他表型及总体样本中无关联，提示静态与动态指标可能反映部分独立的舌运动控制侧面；tVSA 与 FCR 在所有表型中均呈负相关，确认二者是描述元音空间扩大与集中化的互补指标；延髓起病组的 F2 过渡时长与幅度之间无关联，提示其舌运动的空间受限未必与构音速度变化平行。表型比较显示 /e/ 的 F1 及 /a/、/i/、/u/、/o/ 的 F2 存在显著组间差异；静态指标主要与 /a/ 的 F1、/i/ 的 F2 相关，FCR 与 /i/ 的 F2 密切相关。作者认为联合静态（构音位置）与动态（构音过渡）声学指标可多维评估 ALS 舌运动障碍；延髓起病以舌前后向运动受限与垂直调节受损为特征，两者共同导致言语清晰度下降。四、其他神经肌肉疾病（Other Neuromuscular Diseases）超越生物标志物：重申临床神经电生理在神经肌肉疾病中的核心地位 Beyond Biomarkers: Reclaiming the Central Role of Clinical Neurophysiology in Neuromuscular Disorders（Mangiardi M，Brain sciences，2026-09-21） 过去二十年，分子遗传学、免疫学、神经影像、液体生物标志物与人工智能深刻改变了神经肌肉疾病的诊断与分类，但「识别疾病机制」与「刻画机制的功能表达」是两件不同的事。这篇批判性述评以重症肌无力、免疫介导性周围神经病、肌病与 ALS 中的代表性例子，论证临床神经电生理直接评估神经系统功能——冲动传导、神经肌肉传递、运动单位完整性、生理储备与疾病活动度——因而不仅服务诊断，还支撑鉴别诊断、纵向监测、预后评估与疗效评价，这些维度无法被分子与血清学标志物简单替代。文章还讨论了人工智能在信号自动分析与定量评估中的新兴作用，以及在泛化能力、验证与过度依赖模式识别方面的现实局限。作者提出一个互补性概念框架：生物学与分子方法负责刻画疾病机制，临床电生理负责定义其在个体患者中的功能表达与临床相关性——电生理不是精准医学的替代品，而是其整合的生理学维度，把生物学特征与可指导临床决策的功能信息连接起来。对身处「组学时代」的神经肌肉专科医生而言，这是一篇重新定位肌电图与神经传导检查价值的思辨之作。脊肌萎缩症：神经肌肉疾病精准治疗的蓝本 Spinal muscular atrophy as a blueprint for precision therapy in neuromuscular disease（Cetin B, Aliciaslan M, Erbasan E, et al.，Expert reviews in molecular medicine，2026-09-23） SMN1 缺失导致运动神经元生存（SMN）蛋白缺乏、SMN2 拷贝补偿不足，是脊肌萎缩症（SMA）的遗传基础；正是这一清晰的遗传架构，使 SMA 成为神经肌肉疾病精准治疗的「蓝本」。本综述梳理了 SMA 管理的三波治疗浪潮：反义寡核苷酸诺西那生钠（nusinersen）校正 SMN2 剪接；口服小分子剪接调节剂利司扑兰（risdiplam）应对 SMA 作为多系统疾病的全身性治疗需求；基因替代疗法 onasemnogene abeparvovec 提供一次性持久的遗传校正，近期鞘内剂型进一步扩大了可治疗患者范围。精准治疗已深刻改变疾病轨迹，症状前（presymptomatic）治疗获益最为显著；三类药物各有所长——诺西那生钠可持续维持剪接校正，利司扑兰实现中枢与外周组织的 SMN 恢复，基因替代提供持久纠正。但治疗耐久性、最佳治疗排序、系统性受累与长期安全性等关键挑战仍然存在。对整个神经遗传病领域而言，SMA 从被动的对症支持走向主动的分子精准医学的路径，为其他神经肌肉疾病的治疗开发提供了可复制的范式。土耳其黑海中东部地区 DMD 基因变异谱与级联筛查结果：单中心回顾性研究 Mutational Spectrum of DMD Gene Variants and Cascade Screening Outcomes in the Central-Eastern Black Sea Region of Türkiye: A Single-Centre Retrospective Study（Doğan Ç, Aydın S，Molecular biology reports，2026-09-22） 杜氏肌营养不良（DMD）与贝氏肌营养不良（BMD）由 Xp21.2 上 DMD 基因的致病变异引起，但土耳其黑海中东部地区的变异谱此前从未报道。这项单中心回顾性研究纳入 2022 年 1 月至 2026 年 2 月在本中心接受 DMD 检测的全部连续个体共 47 例（女 29、男 18，年龄中位数 12.8 岁），采用 MLPA（45 例可行）与全基因测序（16 例）检测，变异按 2015 ACMG/AMP 与 2020 ACMG/ClinGen 拷贝数标准分类。结果：共发现 19 例携带致病变异，其中先证者 10 例、经级联筛查发现的女性杂合携带者 9 例；先证者检出率 30.3%（10/33，95% CI 17.4-47.3%），级联携带者检出率 64.3%（9/14，95% CI 38.8-83.7%）。变异包括 7 个缺失与 2 个序列变异（NM_004006.3:c.701C>G p.(Ser234Ter)；c.2803+1G>T），9 个家系中 6 个携带远端热点缺失（外显子 45-55）；缺失中 3 个符合读码框、4 个移码。4 例女性杂合子（其中 3 例为先证者）表现为不明原因的高肌酸激酶血症（776-2,816 U/L）而无明确肌无力记录。2 个缺失为明显的新生变异，且无先证者符合已获批外显子跳读寡核苷酸的治疗条件。作者结论：该地区 DMD 变异谱与国家及全球模式基本一致，级联筛查显著扩展了携带者识别，凸显对女性家系成员开展级联检测的必要性。痛性肌萎缩伴膈神经受累患者无创通气成功的预测因素 Predictors for Successful Non-Invasive Ventilation in Patients With Neuralgic Amyotrophy and Phrenic Nerve Involvement（Hendrikx AB, Sprooten RT, Vosse BA, et al.，Muscle & nerve，2026-09-24） 痛性肌萎缩（neuralgic amyotrophy，NA）累及膈神经时可导致膈肌麻痹与呼吸功能不全，长期家庭无创通气（NIV）可能获益，但治疗成功率及其预测因素的数据一直缺乏。本研究回顾性分析荷兰马斯特里赫特家庭机械通气中心 2008 年 9 月至 2023 年 4 月间启动慢性 NIV 的全部 NA 患者。共纳入 54 例（平均年龄 62.5±10.9 岁，男性 72.2%），基线坐位至卧位的用力肺活量下降（ΔFVC）平均为 -35.1%±19.6%，NIV 依从性中位 6.4（3.6-8.1）小时/天。结果显示：平均随访 4.9 年期间，38 例（70.4%）持续使用 NIV，其中 6 例（11%）因临床和/或功能改善成功降级停用；16 例因疗效不佳或不耐受停用。Cox 回归显示，基线 ΔFVC（坐位到卧位）是 NIV 治疗成功的独立预测因素（HR 0.947，95% CI 0.91-0.99），即体位性 FVC 下降越显著者越可能从 NIV 获益。研究支持慢性 NIV 作为 NA 合并膈肌麻痹的长期治疗选择，并提示体位肺功能检查（坐卧位 FVC 对比）有助于筛选最可能获益的患者。CIDP 治疗的药物经济学：IVIG 对比皮下艾加莫德的成本与每应答者成本 Cost comparison of intravenous immunoglobulin and subcutaneous efgartigimod in patients with chronic inflammatory demyelinating polyneuropathy（Muley SA, Gucciardi I, Kaisare V, et al.，Journal of medical economics，2026-09-21） 慢性炎性脱髓鞘性多发性神经根神经病（CIDP）的标准一线治疗是静脉免疫球蛋白（IVIG），而皮下艾加莫德（Vyvgart Hytrulo，efgartigimod alfa 联合透明质酸酶制剂）已成为新的靶向选择，但两者费用差异显著。本研究从美国支付方视角进行成本与每应答者成本分析，比较 6 与 12 个月时间窗内的总治疗费用：Vyvgart Hytrulo 的疗效与应答定义取自 ADHERE 试验，IVIG（Panzyga）取自 ProCID 试验（标准 1 g/kg 与更高 2 g/kg 维持剂量），总费用包含药物获取、给药及按应答状态计的成本（以 2026 年美元计）。结果：6 个月总费用，Panzyga 1 g/kg、Panzyga 2 g/kg 与 Vyvgart Hytrulo 分别为 124,812、217,366 与 464,681 美元；12 个月分别为 190,026、402,301 与 698,583 美元。应答率方面，6 个月分别为 80%、92% 与 53%，12 个月为 74%、85% 与 48%。两个时间点上 Panzyga 的每应答者成本均更低：12 个月时分别为 256,792、473,295 与 1,455,382 美元。作者结论：在本模型假设下，基于 IVIG 的治疗路径总成本与每应答者成本均低于 Vyvgart Hytrulo。需注意本研究缺乏头对头数据、两试验的应答定义存在差异；对国内读者而言，其价值在于展示「每应答者成本」这一药物经济学评价思路，以及 CIDP 生物制剂在国际市场的真实定价量级。日式综合针灸艾灸治疗乳腺癌幸存者紫杉烷类化疗相关周围神经病变：单臂研究 Multimodal Japanese-style acupuncture and moxibustion for taxane-related chemotherapy-induced peripheral neuropathy in breast cancer survivors（Ishiki H, Satomi E, Matsuoka H, et al.，Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer，2026-09-22） 紫杉烷类化疗相关周围神经病变（CIPN）在乳腺癌幸存者中高发，显著影响生活质量，但尚无确立的治疗手段。这项单中心单臂研究评估了日式综合针灸艾灸（MJAM，含毫针针刺、不出针的 Teishin 技术、运动针法、间接艾灸、热敷与自我护理指导）治疗紫杉烷相关 CIPN 的初步疗效与安全性。研究纳入 30 例完成 I-III 期乳腺癌根治性治疗至少 3 个月、存在中重度 CIPN 疼痛（简明疼痛量表 BPI 条目 5 评分 ≥4）的女性（中位年龄 58.0 岁，化疗结束中位时间 2.47 年），接受 12 周每周一次的标准化 MJAM 治疗，主要终点为基线至第 16 周的 BPI 条目 5（平均疼痛）变化。结果：28 例（93.3%）完成全部治疗；基线 BPI 平均疼痛 5.3±1.7 分；评分随时间显著下降——第 4 周 -0.1（95% CI -0.6～0.3，p=0.56）、第 8 周 -0.7（-1.2～-0.2，p=0.008）、第 12 周 -1.1（-1.7～-0.6，p=0.0003）、第 16 周 -1.2（90% CI -1.7～-0.8，p<0.0001）；仅 9 例（30.0%）出现 1 级轻度不良事件。结论：MJAM 安全、可行且与疼痛减轻相关；但作为单臂开放设计缺乏对照，且第 4 周时改善尚未显现，提示需要确证性随机对照试验验证（注册号 UMIN-CTR UMIN000048478）。严重热射病恢复期并发 AMSAN 型吉兰-巴雷综合征：病例报告与文献复习 Multiple organ failure following severe heat stroke complicated by AMSAN-type Guillain-Barré syndrome: a case report and literature review（Zhang Y, Yin J, Lu J, et al.，BMC neurology，2026-09-22） 热射病是最严重的中暑类型，可触发全身炎症反应与细胞因子风暴、扰乱免疫稳态，但热射病恢复期合并吉兰-巴雷综合征（GBS）的报道极为罕见，两者关系尚不明确。本文报告 1 例既往健康的 57 岁男性，远足途中出现意识模糊与高热，随后进展为多器官功能衰竭，初期按热射病治疗；神志恢复后出现四肢肌张力减低与感觉障碍，经检查确诊为急性运动感觉轴索性神经病（AMSAN）型 GBS——一种以轴索损伤为主的 GBS 亚型。患者在接受血浆置换、静脉免疫免疫球蛋白及康复治疗后神经功能逐步改善。作者将该病例与已发表的热射病时间关联性 GBS 报道进行对比复习，认为热射病可能通过严重全身炎症与免疫失调充当了 GBS 的「非典型免疫触发因素」。临床启示：热射病恢复期出现进行性神经功能缺损时应高度警惕 GBS，及时的神经电生理与脑脊液评估对早期诊断和干预、改善预后至关重要。抗 OJ 抗体阳性抗合成酶综合征合并肝细胞癌：一例副肿瘤性病例报告 Anti-OJ antibody-positive anti-synthetase syndrome associated with hepatocellular carcinoma（Tachi K, Kita M, Kawakita R, et al.，BMJ case reports，2026-09-22） 抗合成酶综合征（ASS）是以抗氨酰 tRNA 合成酶抗体为特征的罕见自身免疫病，可表现为肌炎、间质性肺病与关节炎等；抗 OJ 抗体（抗异亮氨酰 tRNA 合成酶）尤其罕见，常规检测易出现假阴性而漏诊。本文报告 1 例 70 多岁男性肝细胞癌（HCC）患者，表现为进行性近端肌无力与垂头综合征（dropped head syndrome），检查发现肌酸激酶升高、肌肉影像异常及肌源性改变；常规血清学检测阴性，但基于小麦胚无细胞蛋白合成系统的新一代检测（A-cube）确认抗 OJ 抗体阳性；肌活检显示坏死与再生纤维，无束周坏死。患者接受肝叶切除术后，肌无力与实验室异常在未行任何免疫治疗的情况下改善。这是第 2 例抗 OJ 抗体阳性 ASS 合并 HCC 的报道，两例患者均在肿瘤切除后不经免疫抑制治疗而缓解。本例凸显了新一代血清学检测平台（如无细胞蛋白合成系统）在罕见肌炎抗体识别中的诊断价值，并提示抗 OJ 阳性 ASS 可能呈副肿瘤性，针对潜在恶性肿瘤的治疗或可成为缓解的关键。本周小结 MG：生物制剂的「间接比较」与真实世界安全性证据集中出炉。 本周 4 篇 MG 治疗学文献构成一个完整的证据群：九药方案分层贝叶斯 MBMA 提示 FcRn 抑制剂在客观运动量表（QMG）上可能优于补体抑制剂（后验概率 99.7%），zilucoplan 与 rozanolixizumab 两项 MAIC 均给出与 IVIG 或同类药物的比较排序，艾加莫德「个体化间隔给药维持轻微症状」试验方案则展示了长期降阶梯管理的思路；与此同时，覆盖 5.6 万患者年的美国真实世界数据继续显示补体终末抑制剂的脑膜炎奈瑟菌感染率稳定处于低位。需要提醒：MAIC/MBMA 均为模型推断而非头对头证据，可作为选药参考但不宜直接等同于疗效结论。 ALS：遗传机制向「家族性/散发性」边界与炎症性细胞死亡两端推进。 Brain 的跨大洲 IBD 研究用 3,524 人队列证明，相当比例的「散发性」ALS 实为被外显率减低掩盖的遗传病；Cell Death & Differentiation 的 TBK1-GSDME 焦亡轴研究把不同基因型的致病信号汇聚到共同的炎症性细胞死亡程序；Acta Neuropathologica 则把 C9ORF72 相关的 TDP-43 功能缺失效应推进到突触末端的隐秘转录本。临床端，441 例延髓起病自然史、步态-跌倒前瞻队列与营养量表预后研究，继续强化分期管理与多维度预后评估的实践基础。 其他 NMD：从「有没有药」走向「用得准、用得起」。 SMA 精准治疗范式综述系统复盘了诺西那生钠、利司扑兰与基因替代三波疗法；DMD 单中心系列强调级联筛查对女性携带者识别的价值（检出率 64.3%）；CIDP 的 IVIG 对比皮下艾加莫德药物经济学分析引入「每应答者成本」概念（12 个月 25.7 万 vs 145.5 万美元），为高价生物制剂时代的治疗选择提供了量化框架。此外，痛性肌萎缩膈神经受累的 NIV 预测研究、热射病恢复期 AMSAN 病例与抗 OJ 副肿瘤性肌炎病例，提醒临床对罕见表型的识别与鉴别。参考文献 Vakrakou AG, Belimezi M, Strataki E, Kontizas E, Tzavella D, Panaretos D et al. 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PMID: 42772928. https://pubmed.ncbi.nlm.nih.gov/42772928/[26] 声明：本速递基于 PubMed 数据库公开元数据与官方摘要翻译整理，摘要要点为编译概括而非逐句翻译；文献收录可能存在滞后或遗漏，引用前请务必核对原文。引用链接 [1]https://pubmed.ncbi.nlm.nih.gov/42786377/ [2]https://pubmed.ncbi.nlm.nih.gov/42790255/ [3]https://pubmed.ncbi.nlm.nih.gov/42786374/ [4]https://pubmed.ncbi.nlm.nih.gov/42786373/ [5]https://pubmed.ncbi.nlm.nih.gov/42768201/ [6]https://pubmed.ncbi.nlm.nih.gov/42786372/ [7]https://pubmed.ncbi.nlm.nih.gov/42776983/ [8]https://pubmed.ncbi.nlm.nih.gov/42777931/ [9]https://pubmed.ncbi.nlm.nih.gov/42778785/ [10]https://pubmed.ncbi.nlm.nih.gov/42768102/ [11]https://pubmed.ncbi.nlm.nih.gov/42789481/ [12]https://pubmed.ncbi.nlm.nih.gov/42789089/ [13]https://pubmed.ncbi.nlm.nih.gov/42770300/ [14]https://pubmed.ncbi.nlm.nih.gov/42771573/ [15]https://pubmed.ncbi.nlm.nih.gov/42763209/ [16]https://pubmed.ncbi.nlm.nih.gov/42782389/ [17]https://pubmed.ncbi.nlm.nih.gov/42786852/ [18]https://pubmed.ncbi.nlm.nih.gov/42771575/ [19]https://pubmed.ncbi.nlm.nih.gov/42793425/ [20]https://pubmed.ncbi.nlm.nih.gov/42776081/ [21]https://pubmed.ncbi.nlm.nih.gov/42771065/ [22]https://pubmed.ncbi.nlm.nih.gov/42781789/ [23]https://pubmed.ncbi.nlm.nih.gov/42764727/ [24]https://pubmed.ncbi.nlm.nih.gov/42768220/ [25]https://pubmed.ncbi.nlm.nih.gov/42773424/ [26]https://pubmed.ncbi.nlm.nih.gov/42772928/

LB2102 demonstrated a manageable safety profile and encouraging clinical activity in solid tumors among heavily pretreated patients Responses observed at higher dose levels of LB2102 with an ORR of 28.6% and a DCR of 78.6%, with durable responses seen in some patients New CARVYKTI® data continue to support durable efficacy and a consistent safety profile in multiple myeloma BRIDGEWATER, N.J., June 01, 2026 (GLOBE NEWSWIRE) -- Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech or the Company), a global leader in cell therapy, today announced first-in-human clinical data for LB2102, its investigational DLL3-targeted CAR-T cell therapy for patients with relapsed or refractory small cell lung cancer (SCLC) or large-cell neuroendocrine carcinoma (LCNEC). The data demonstrate early evidence of clinical activity and a manageable safety profile. At higher dose levels, an objective response rate (ORR) of 28.6% and disease control rate (DCR) of 78.6% were observed, including durable responses in some heavily pretreated patients. The data, presented in a rapid oral presentation (Abstract #8012) at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, support the clinical potential of CAR-T cell therapy in solid tumors. Additionally, new analyses from the CARTITUDE program were presented, further highlighting sustained clinical benefit and a consistent safety profile for CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) in multiple myeloma. “The data presented at ASCO underscores the progress of our next-generation pipeline and the meaningful impact that CARVYKTI continues to deliver to patients,” said Ying Huang, Ph.D., Chief Executive Officer of Legend Biotech. “LB2102 marks an early step in expanding CAR-T cell therapy into solid tumors, addressing the unique challenges where current treatment options are limited and early data show promising clinical activity in difficult-to-treat cancers. At the same time, CARVYKTI continues to demonstrate durable efficacy and a consistent safety profile, reinforcing its role as a transformative therapy for multiple myeloma and supporting our leadership in cell therapy.” LB2102: Early Evidence of Clinical Activity Observed in Solid Tumors Early Phase 1 results from the ongoing study of LB2102 demonstrate encouraging anti-tumor activity and a manageable safety profile in patients with relapsed or refractory (R/R) SCLC or LCNEC, a population characterized by advanced disease and limited treatment options. LB2102 is an investigational DLL3-targeted autologous CAR-T cell therapy with dnTGFBR2 Armor engineered to enhance activity by overcoming immunosuppressive signaling within the tumor microenvironment. Efficacy Results Objective response rate (ORR): 20% (4/20)Disease control rate (DCR): 70% (14/20)At dose level ≥3: ORR: 28.6%DCR: 78.6%Median duration of disease control: 6.1 months Median duration of response: 6.5 monthsOngoing responses were observed in 2 patients at data cutoff Safety Results No dose-limiting toxicities or treatment-related deathsCytokine release syndrome (CRS) occurred in 30% of patients (all Grade ≤2)Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 15% of patients (two Grade 1 and one Grade 3)Most Grade ≥3 adverse events were hematologic and co-attributed to lymphodepletion “Patients with relapsed or refractory SCLC or LCNEC have historically had very limited treatment options and poor outcomes,” said Zhonglin Hao, M.D., Ph.D., Professor of Medicine and Cancer Biology, Director, Thoracic Oncology Program, University of Kentucky Markey Cancer Center. “Durable disease control and responses at higher dose levels with LB2102 are encouraging, particularly alongside a manageable safety profile. These findings support continued evaluation of CAR-T approaches in solid tumors, where effective therapies remain limited.”‡ LB2102 represents part of the Company’s broader strategy to expand CAR-T therapies beyond hematologic malignancies and into solid tumors. In November 2023, Legend Biotech’s subsidiary, Legend Biotech Ireland Limited, entered into a license agreement with Novartis Pharma AG (the Novartis Agreement), granting Novartis an exclusive worldwide license to develop, manufacture, and commercialize certain Legend Biotech CAR-T cell therapies targeting DLL3. Under the Novartis Agreement, Legend Biotech is responsible for conducting the current Phase 1 clinical trial of LB2102 in the United States, while Novartis is responsible for conducting all other development, manufacturing, and commercialization for the licensed products, including LB2102. CARVYKTI®: Ongoing Clinical Data in Multiple Myeloma New analyses from the CARTITUDE program continue to demonstrate sustained clinical benefit and consistent safety profile of CARVYKTI® in patients with multiple myeloma. In the CARTITUDE-4 subgroup analysis (Abstract #7536), progression-free survival and overall survival benefits were observed across both high-risk and standard-risk cytogenetic populations among patients who responded to bridging therapy, with 30-month OS rates greaterthan 85%.No cases of immune effector cell (IEC)–associated Parkinsonism were reported. In a separate multi-study analysis (Abstract #7533), a low incidence (1.2%) of IEC-associated enterocolitis (IEC-EC) was observed, further characterizing this uncommon adverse event and reinforcing the overall favorable benefit-risk profile of CARVYKTI®. CARVYKTI® is the first and only BCMA-targeted CAR-T cell therapy approved for the treatment of patients with multiple myeloma who have had at least one prior line of therapy. Globally, CARVYKTI® is now commercially available in 18 countries and has been used to treat more than 10,000 patients to date. CARVYKTI® IMPORTANT SAFETY INFORMATION WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, PROLONGED and RECURRENT CYTOPENIA, and SECONDARY HEMATOLOGICAL MALIGNANCIESCytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with CARVYKTI®. Do not administer CARVYKTI® to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS), which may be fatal or life-threatening, occurred following treatment with CARVYKTI®, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with CARVYKTI®. Provide supportive care and/or corticosteroids as needed.Parkinsonism and Guillain-Barré syndrome (GBS) and their associated complications resulting in fatal or life-threatening reactions have occurred following treatment with CARVYKTI®.Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), including fatal and life-threatening reactions, occurred in patients following treatment with CARVYKTI®. HLH/MAS can occur with CRS or neurologic toxicities.Prolonged and/or recurrent cytopenias with bleeding and infection and requirement for stem cell transplantation for hematopoietic recovery occurred following treatment with CARVYKTI®.Immune Effector Cell-associated Enterocolitis (IEC-EC), including fatal or life-threatening reactions, occurred following treatment with CARVYKTI®.Secondary hematological malignancies, including myelodysplastic syndrome and acute myeloid leukemia, have occurred in patients following treatment with CARVYKTI®. T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including CARVYKTI®. 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 ENTERCOLITIS (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 REACTIONSThe 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 CARVYKTI® (CILTACABTAGENE AUTOLEUCEL; CILTA-CEL)Ciltacabtagene autoleucel is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient’s own T-cells with a transgene encoding a chimeric antigen receptor (CAR) that identifies and eliminates cells that express BCMA. The cilta-cel CAR protein features two BCMA-targeting single-domain antibodies 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.i In December 2017, Legend Biotech entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc., a Johnson & Johnson company, to develop and commercialize cilta-cel. In February 2022, cilta-cel was approved by the U.S. Food and Drug Administration (FDA) under the brand name CARVYKTI® for the treatment of adults with relapsed or refractory multiple myeloma. In April 2024, cilta-cel was approved for the second-line treatment of patients with relapsed/refractory myeloma who have received at least one prior line of therapy, including a proteasome inhibitor, an immunomodulatory agent, and are refractory to lenalidomide. In May 2022, the European Commission (EC) granted conditional marketing authorization of CARVYKTI® for the treatment of adults with relapsed and refractory multiple myeloma. In September 2022, Japan’s Ministry of Health, Labour and Welfare (MHLW) approved CARVYKTI®. Cilta-cel was granted Breakthrough Therapy Designation in the U.S. in December 2019 and in China in August 2020. In addition, cilta-cel received a PRIority MEdicines (PRIME) designation from the European Commission in April 2019. Cilta-cel also received Orphan Drug Designation from the U.S. FDA in February 2019, from the European Commission in February 2020, and from the Pharmaceuticals and Medicinal Devices Agency (PMDA) in Japan in June 2020. In March 2022, the European Medicines Agency’s Committee for Orphan Medicinal Products recommended by consensus that the orphan designation for cilta-cel be maintained on the basis of clinical data demonstrating improved and sustained complete response rates following treatment. ABOUT MULTIPLE MYELOMAMultiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells.ii In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma, and more than 12,000 people will die from the disease in the U.S.iii While some patients with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems, or infections.iv ABOUT CARTITUDE-4CARTITUDE-4 (NCT04181827) is an ongoing, international, randomized, open-label Phase 3 study evaluating the efficacy and safety of cilta-cel versus pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd) in adult patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy, including a PI and an IMiD.v ABOUT LB2102NCT05680922 is a Phase 1, first-in-human, open-label, multicenter, dose escalation and expansion study of DLL3-targeted chimeric antigen receptor T-cells (LB2102) in patients with extensive stage small cell lung cancer or large cell neuroendocrine lung cancer.vi ABOUT SMALL-CELL LUNG CANCERLung cancer is a leading cause of cancer deaths, contributing to 25 percent of all cancer-related fatalities annually in the United States.vii Small cell lung cancer (SCLC) is the most aggressive, and accounts for roughly 10-15 percent of lung cancer cases in the United States.viii,ix An estimated 30,000 to 35,000 people are newly diagnosed with the disease each year. This cancer becomes more difficult to treat once it has spread and becomes extensive stage SCLC. Approximately 60 to 70 percent of SCLC patients are diagnosed with metastatic SCLC.,x ABOUT LEGEND BIOTECHWith over 3,000 employees, Legend Biotech is the largest standalone cell therapy company and a pioneer in treatments that change cancer care forever. Legend Biotech is at the forefront of the CAR-T cell therapy revolution with CARVYKTI®, a one-time treatment for relapsed or refractory multiple myeloma, which it develops and markets with collaborator Johnson & Johnson. Centered in the United States, Legend Biotech is building an end-to-end cell therapy company by expanding its leadership to maximize CARVYKTI’s patient access and therapeutic potential. From this platform, Legend Biotech plans to drive future innovation across its pipeline of cutting-edge cell therapy modalities. Learn more at https://legendbiotech.com and follow us on X, Instagram, and LinkedIn. CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTSStatements in this press release about future expectations, plans, and prospects, as well as any other statements regarding matters that are not historical facts, constitute “forward-looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to: Legend Biotech’s strategies and objectives; the benefits of CARVYKTI, including its emerging curative potential; and the potential of LB2102, including the reproducibility and durability of any favorable results initially seen in patients dosed to date in clinical trials. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors. Legend Biotech’s expectations could be affected by, among other things, uncertainties involved in the development of new pharmaceutical products; unexpected clinical trial results, including as a result of additional analysis of existing clinical data or unexpected new clinical data; unexpected regulatory actions or delays, including requests for additional safety and/or efficacy data or analysis of data, or government regulation generally; unexpected delays as a result of actions undertaken, or failures to act, by our third-party partners; uncertainties arising from challenges to Legend Biotech’s patent or other proprietary intellectual property protection, including the uncertainties involved in the U.S. litigation process; government, industry, and general product pricing and other political pressures; as well as the other factors discussed in the “Risk Factors” section of Legend Biotech’s Annual Report on Form 20-F filed with the Securities and Exchange Commission on March 10, 2026. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described in this press release as anticipated, believed, estimated, or expected. Any forward-looking statements contained in this press release speak only as of the date of this press release. Legend Biotech specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events, or otherwise. ‡ Zhonglin Hao, M.D., Ph.D., Professor of Medicine and Cancer Biology, Director, Thoracic Oncology Program, University of Kentucky Markey Cancer Center, has provided consulting and advisory services to Legend Biotech; he has not been paid for any media work. INVESTOR CONTACT:Jessie YeungTel: (732) 956-8271investor@legendbiotech.com PRESS CONTACT:Kim FoxTel: (848) 388-8445media@legendbiotech.com i CARVYKTI™ Prescribing Information. Horsham, PA: Janssen Biotech, Inc.ii American Cancer Society. “What is Multiple Myeloma?”. Available at: https://www.cancer.org/cancer/types/multiple-myeloma/about/what-is-multiple-myeloma.html.Accessed March 2024.iii American Cancer Society. “Key Statistics About Multiple Myeloma.” Available at: https://www.cancer.org/cancer/types/multiple-myeloma/about/key-statistics.html.Accessed March 2024.iv American Cancer Society. Multiple myeloma: early detection, diagnosis, and staging. Available at: https://www.cancer.org/content/dam/CRC/PDF/Public/8740.00.pdf. Accessed March 2023.v ClinicalTrials.Gov. A Study Comparing JNJ-68284528, a CAR-T Therapy Directed Against B-cell Maturation Antigen (BCMA), Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Participants With Relapsed and Lenalidomide-Refractory Multiple Myeloma (CARTITUDE-4). https://www.clinicaltrials.gov/study/NCT04181827. Accessed March 2024.vi ClinicalTrials.gov. DLL3-Directed Chimeric Antigen Receptor T-cells in Subjects With Extensive Stage Small Cell Lung Cancer. Available at: https://www.clinicaltrials.gov/study/NCT05680922. Accessed May 2025vii American Cancer Society. “Key Statistics for Lung Cancer.” https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html. Accessed November 2022.viii Byers LA, Rudin CM. Small cell lung cancer: where do we go from here? Cancer. 2015;121(5):664-72.ix Rare Diseases. “Rare Disease Database.” https://rarediseases.org/rare-diseases/small-cell-lung-cancer. Accessed November 2022.x Gong J, Salgia R. Managing patients with relapsed small-cell lung cancer. J Oncol Pract. 2018;14(6):359-66.