RARITAN, N.J., March 15, 2024  /PRNewswire/ -- Johnson & Johnson announced today that the U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) recommends CARVYKTI® (ciltacabtagene autoleucel, cilta-cel) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) and who are refractory to lenalidomide.

新泽西州拉瑞坦（RARITAN），2024年3月15日/PRNewswire/--强生公司今天宣布，美国食品和药物管理局（FDA）肿瘤药物咨询委员会（ODAC）推荐CARVYKTI®（ciltacabtagene autoleucel，cilta cel）用于治疗复发或难治性多发性骨髓瘤的成年患者，这些患者至少接受过一种先前的治疗方案，包括蛋白酶体抑制剂（PI）和免疫调节剂（IMiD），并且对来那度胺难治。

The committee reviewed survival and safety data from the Phase 3 CARTITUDE-4 study and voted unanimously in favor of CARVYKTI® (11 to 0) finding the risk-benefit assessment of CARVYKTI® for the proposed indication as favorable. A supplemental Biologics License Application (sBLA) supported by the CARTITUDE-4 study is currently under review by the FDA with a Prescription Drug User Fee Act (PDUFA) date of April 5, 2024. .

委员会审查了来自第3阶段CARTITUDE-4研究的生存和安全性数据，并一致投票赞成CARVYKTI®（11比0），认为CARVYKTI®对拟议适应症的风险-效益评估是有利的。由Cartitute-4研究支持的补充生物制剂许可证申请（sBLA）目前正在由FDA审查，处方药用户费用法案（PDUFA）日期为2024年4月5日。

'We are pleased with the advisory committee's support for CARVYKTI in earlier lines of treatment based on the CARTITUDE-4 data,' said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Johnson & Johnson Innovative Medicine. 'As a physician and researcher committed to advancing patient care, the potential of CARVYKTI in earlier lines of therapy represents an important therapeutic option for patients with multiple myeloma.'.

强生创新医学公司（Johnson＆Johnson Innovative Medicine）多发性骨髓瘤疾病领域负责人、副总裁乔丹·谢克特（Jordan Schecter）医学博士（M.D.）说，我们很高兴咨询委员会根据Cartitute-4数据支持CARVYKTI早期治疗方案作为一名致力于推进患者护理的医生和研究人员，CARVYKTI在早期治疗中的潜力代表了多发性骨髓瘤患者的重要治疗选择。”。

The committee reviewed data from the CARTITUDE-4 study, the first randomized Phase 3 study of CARVYKTI®, which evaluated the efficacy and safety of CARVYKTI® versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in the treatment of patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy.1 These data also served as the basis for the recent European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) positive opinion of a Type II variation for CARVYKTI® in the treatment of patients with relapsed and refractory multiple myeloma who have received at least one prior therapy, including an IMiD and a PI, and are refractory to lenalidomide.2 Results from the CARTITUDE-4 study were initially presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine.1,3 .

委员会审查了CARVYKTI®的第一项随机3期研究Cartitute-4研究的数据，该研究评估了CARVYKTI®与pomalidomide，硼替佐米和地塞米松（PVd）或daratumumab，pomalidomide和地塞米松（DPd）的疗效和安全性用于治疗复发性和来那度胺难治性多发性骨髓瘤患者，这些患者曾接受过一到三种治疗方案。1这些数据也为最近的欧洲药品管理局（EMA）人类使用药品委员会（CHMP）提供了基础CARVYKTI®II型变异在治疗复发和难治性多发性骨髓瘤患者中的积极意见，这些患者至少接受过一次治疗，包括IMiD和PI，并且对来那度胺难治。2 Cartitute-4研究的结果最初在2023年美国临床肿瘤学会（ASCO）上发表年会并发表在《新英格兰医学杂志》上。

'Multiple myeloma is a disease with high unmet need as patients experience relapse or become refractory to treatments over time,' said Sundar Jagannath, M.D., Director of the Center of Excellence for Multiple Myeloma and Professor of Medicine, Hematology and Medical Oncology, Mount Sinai.‡ 'The availability of a cellular therapy like cilta-cel that can be used earlier in the treatment of this progressive disease is critically important, offering patients a chance of deep and durable responses with a one-time infusion.'.

多发性骨髓瘤卓越中心主任、西奈山医学、血液学和医学肿瘤学教授SundarJagannath医学博士说：“随着时间的推移，患者复发或难以治疗，多发性骨髓瘤是一种未满足需求的疾病。”可以早期用于治疗这种进行性疾病的细胞疗法（如cilta-cel）的可用性至关重要，为患者提供了一次性输注深度和持久反应的机会。”

The ODAC is convened upon request of the FDA to review and evaluate safety and efficacy data of human drug products for use in the treatment of oncologic diseases. The committee provides non-binding recommendations based on its evaluation; however, final decisions on approval of the drug are made by the FDA..

ODAC应FDA的要求召开，以审查和评估用于治疗肿瘤疾病的人类药物产品的安全性和有效性数据。委员会根据其评估提出不具约束力的建议；然而，批准该药物的最终决定是由FDA做出的。

About CARVYKTI® (ciltacabtagene autoleucel; cilta-cel)

关于CARVYKTI®[UNK]（自白细胞血症；cylta细胞）

CARVYKTI® 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 PI, an IMiD agent, and an anti-CD38 monoclonal antibody.4 In May 2022, the European Commission granted conditional marketing authorization of CARVYKTI® for the treatment of adults with relapsed and refractory multiple myeloma who have received at least three prior therapies, including an IMiD agent, a PI and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy..

CARVYKTI®于2022年2月获得美国食品和药物管理局的批准，用于治疗四种或四种以上先前治疗方案（包括PI，IMiD药物和抗CD38单克隆抗体）后复发或难治性多发性骨髓瘤的成年人。4 2022年5月，欧盟委员会授予CARVYKTI®有条件上市许可，用于治疗复发和难治性多发性骨髓瘤的成年人，这些成年人至少接受过三种治疗，包括IMiD药物，PI和抗CD38抗体，并在最后一次治疗中证明了疾病进展。

CARVYKTI® is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which 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.

CARVYKTI®是一种BCMA指导的基因修饰自体T细胞免疫疗法，它涉及用编码嵌合抗原受体（CAR）的转基因重新编程患者自身的T细胞，该转基因指导CAR阳性T细胞消除表达BCMA的细胞。BCMA主要在恶性多发性骨髓瘤B系细胞以及晚期B细胞和浆细胞的表面表达。

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..

CARVYKTI®CAR蛋白具有两个BCMA靶向单结构域，旨在赋予对人BCMA的高亲和力。在与表达BCMA的细胞结合后，CAR促进T细胞活化，扩增和消除靶细胞。

In December 2017, Janssen Biotech, Inc. entered into an exclusive worldwide license and collaboration agreement with Legend Biotech USA, Inc. to develop and commercialize CARVYKTI®.

2017年12月，Janssen Biotech，Inc.与Legend Biotech USA，Inc.签订了独家全球许可和合作协议，以开发和商业化CARVYKTI®。

For more information, visit www.CARVYKTI.com.

有关更多信息，请访问www.CARVYKTI.com。

About multiple myeloma

关于多发性骨髓瘤

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.

多发性骨髓瘤是一种无法治愈的血癌，会影响一种称为浆细胞的白细胞，这种白细胞存在于骨髓中。5在多发性骨髓瘤中，这些浆细胞迅速增殖和扩散，并用肿瘤替代骨髓中的正常细胞。6多发性骨髓瘤是全球第三大常见血癌，仍然是一种无法治愈的疾病。7 2024年，据估计，美国将有超过35000人被诊断出患有多发性骨髓瘤。

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.

超过12000人将死于这种疾病。8名多发性骨髓瘤患者的5年生存率为59.8%。9虽然一些被诊断为多发性骨髓瘤的患者最初没有症状，但大多数患者被诊断出的症状可能包括骨折或疼痛，红细胞计数低，疲倦，钙水平高以及肾脏问题或感染[10,11]。

CARVYKTI® IMPORTANT SAFETY INFORMATION

CARVYKTI®重要安全信息

WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, and PROLONGED and RECURRENT CYTOPENIA   Cytokine 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.

警告：用CARVYKTI®治疗后的患者发生细胞因子释放综合征，神经毒性，HLH/MAS以及长期和复发性血细胞减少症细胞因子释放综合征（CRS），包括致命或危及生命的反应。请勿将CARVYKTI®用于活动性感染或炎症性疾病患者。

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.

用托珠单抗或托珠单抗和皮质类固醇治疗严重或危及生命的CRS。免疫效应细胞相关神经毒性综合征（ICANS）可能致命或危及生命，发生在用CARVYKTI®治疗后，包括在CRS发作之前，与CRS同时发生，在CRS消退后或在没有CRS的情况下。

Monitor for neurologic events after treatment with CARVYKTI®. Provide supportive care and/or corticosteroids as needed.    Parkinsonism and Guillain-Barré syndrome 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®.

用CARVYKTI®治疗后监测神经系统事件。根据需要提供支持性护理和/或皮质类固醇。在用CARVYKTI®治疗后，发生了帕金森病和格林-巴利综合征及其相关并发症，导致致命或危及生命的反应。CARVYKTI®治疗后的患者发生噬血细胞性淋巴组织细胞增多症/巨噬细胞活化综合征（HLH/MAS），包括致命和危及生命的反应。

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®.    CARVYKTI® is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI® REMS Program.  .

HLH/MAS可伴有CRS或神经系统毒性。在用CARVYKTI®治疗后，发生了长时间和/或复发性血细胞减少症，伴有出血和感染，并且需要进行干细胞移植以恢复造血功能。CARVYKTI®只能通过风险评估和缓解策略（REMS）下的受限计划（称为CARVYKTI®REMS计划）获得。

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.

根据临床表现确定CRS。评估和治疗发烧、缺氧和低血压的其他原因。据报道，CRS与HLH/MAS的发现有关，这些综合征的生理学可能重叠。HLH/MAS是一种潜在的威胁生命的疾病。尽管接受了治疗，但仍有CRS或难治性CRS进行性症状的患者，请评估HLH/MAS的证据。

Monitor patients at least daily for 10 days following CARVYKTI® infusion at a REMS-certified healthcare facility for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 4 weeks after infusion. At the first sign of CRS, immediately institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids. .

在REMS认证的医疗机构输注CARVYKTI®后，至少每天监测患者CRS的体征和症状10天。输注后至少4周监测患者CRS的体征或症状。在CRS的第一个迹象时，立即用支持治疗，托珠单抗或托珠单抗和皮质类固醇进行治疗。。

Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time.

如果CRS的体征或症状随时出现，建议患者立即就医。

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, Guillain-Barré Syndrome, immune mediated myelitis, peripheral neuropathies, and cranial nerve palsies.

在用CARVYKTI®治疗后，可能发生严重，危及生命或致命的神经系统毒性。神经系统毒性包括ICANS，伴有帕金森病症状和体征的神经系统毒性，格林-巴利综合征，免疫介导的脊髓炎，周围神经病和颅神经麻痹。

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. .

就这些神经系统毒性的体征和症状以及其中一些毒性发作的延迟性质向患者提供咨询。指示患者在任何时候出现任何这些神经系统毒性的体征或症状时，立即寻求医疗护理以进行进一步评估和管理。。

Overall, one or more subtypes of neurologic toxicity described below occurred following ciltacabtagene autoleucel in 26% (25/97) of patients, of which 11% (11/97) of patients experienced Grade 3 or higher events. These subtypes of neurologic toxicities were also observed in two ongoing studies.

总体而言，在26%（25/97）的患者中发生了西他卡本自体白血病后发生的一种或多种神经毒性亚型，其中11%（11/97）的患者发生了3级或更高级别的事件。在两项正在进行的研究中也观察到了这些亚型的神经毒性。

Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): Patients 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. ICANS occurred in 23% (22/97) of patients receiving ciltacabtagene autoleucel including Grade 3 or 4 events in 3% (3/97) and Grade 5 (fatal) events in 2% (2/97).

免疫效应细胞相关神经毒性综合征（ICANS）：接受CARVYKTI®治疗后，患者可能会出现致命或危及生命的ICANS，包括CRS发作前，CRS消退后，或无CRS时。23%（22/97）接受ciltacabtagene autoleucel治疗的患者发生ICANS，包括3%（3/97）和5级（致命）的3级或4级事件事件发生率为2%（2/97）。

The median time to onset of ICANS was 8 days (range 1-28 days). All 22 patients with ICANS had CRS. The most frequent (≥5%) manifestation of ICANS included encephalopathy (23%), aphasia (8%) and headache (6%). .

ICANS发病的中位时间为8 天（范围1-28天）。所有22例ICANS患者均患有CRS。ICANS最常见（≥5%）的表现包括脑病（23%），失语（8%）和头痛（6%）。

Monitor patients at least daily for 10 days following CARVYKTI® infusion at the REMS certified healthcare facility for signs and symptoms of ICANS. Rule out other causes of ICANS symptoms. Monitor patients for signs or symptoms of ICANS for at least 4 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed. .

在REMS认证的医疗机构输注CARVYKTI®后，至少每天监测患者10天，以了解ICAN的体征和症状。排除ICANS症状的其他原因。输注后至少4周监测患者的ICAN体征或症状，并及时治疗。神经系统毒性应根据需要给予支持治疗和/或皮质类固醇。

Parkinsonism: Of the 25 patients in the CARTITUDE-1 study experiencing any neurotoxicity, five male patients had neurologic toxicity with several signs and symptoms of parkinsonism, distinct from immune effector cell-associated neurotoxicity syndrome (ICANS). Neurologic toxicity with parkinsonism has been reported in other ongoing trials of ciltacabtagene autoleucel.

帕金森病：在Cartitute-1研究中的25名患者中，有5名男性患者有神经毒性，伴有帕金森病的几种体征和症状，不同于免疫效应细胞相关神经毒性综合征（ICANS）。其他正在进行的ciltacabtagene autoleucel试验也报道了帕金森病的神经毒性。

Patients had parkinsonian and non-parkinsonian symptoms that included tremor, bradykinesia, involuntary movements, stereotypy, loss of spontaneous movements, masked facies, apathy, flat affect, fatigue, rigidity, psychomotor retardation, micrographia, dysgraphia, apraxia, lethargy, confusion, somnolence, loss of consciousness, delayed reflexes, hyperreflexia, memory loss, difficulty swallowing, bowel incontinence, falls, stooped posture, shuffling gait, muscle weakness and wasting, motor dysfunction, motor and sensory loss, akinetic mutism, and frontal lobe release signs.

患者有帕金森氏症和非帕金森氏症症状，包括震颤，运动迟缓，不自主运动，刻板印象，自发运动丧失，掩蔽相，冷漠，情绪平缓，疲劳，僵硬，精神运动迟缓，显微照相，书写困难，失用，嗜睡，困惑，嗜睡，意识丧失，反射延迟，反射亢进，记忆力丧失，吞咽困难，大便失禁，跌倒，弯腰姿势，步态蹒跚，肌肉无力和消瘦，运动功能障碍，运动和感觉丧失，运动性缄默症和额叶释放体征。

The median onset of parkinsonism in the 5 patients in CARTITUDE-1 was 43 days (range 15-108) from infusion of ciltacabtagene autoleucel. .

Cartitute-1的5例患者帕金森病的中位发病率为43 输注ciltacabtagene autoleucel的天数（范围15-108）。

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. .

监测患者帕金森病的体征和症状，这些症状可能会延迟发作，并通过支持性护理措施进行管理。用于治疗帕金森病的药物的疗效信息有限，用于改善或解决CARVYKTI®治疗后的帕金森氏症症状。

Guillain-Barré Syndrome: A fatal outcome following Guillain-Barré Syndrome (GBS) has occurred in another ongoing study of ciltacabtagene autoleucel despite treatment with intravenous immunoglobulin (IVIG). Symptoms reported include those consistent with Miller-Fisher variant of GBS, encephalopathy, motor weakness, speech disturbances and polyradiculoneuritis. .

吉兰-巴雷综合征：吉兰-巴雷综合征（GBS）后的致命结果发生在另一项正在进行的西他卡本自体白血病研究中，尽管使用静脉注射免疫球蛋白（IVIG）治疗。报告的症状包括与GBS的Miller-Fisher变体一致的症状，脑病，运动无力，言语障碍和多发性神经根炎。

Monitor for GBS. Evaluate patients presenting with peripheral neuropathy for GBS. Consider treatment of GBS with supportive care measures and in conjunction with immunoglobulin and plasma exchange, depending on severity of GBS.

监测GBS。评估患有GBS周围神经病变的患者。根据GBS的严重程度，考虑采用支持性护理措施并结合免疫球蛋白和血浆置换治疗GBS。

Immune Mediated Myelitis: Grade 3 myelitis has occurred 25 days following treatment in another ongoing study. 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 immunoglobulin.

免疫介导的脊髓炎：在另一项正在进行的研究中，治疗后25天发生了3级脊髓炎。报告的症状包括下肢和下腹感觉减退，括约肌控制受损。使用皮质类固醇和静脉注射免疫球蛋白可改善症状。

Myelitis was ongoing at the time of death from other cause. .

脊髓炎在其他原因死亡时正在进行中。

Peripheral Neuropathy: Six patients in CARTITUDE-1 developed peripheral neuropathy. These neuropathies presented as sensory, motor or sensorimotor neuropathies. Median time of onset of symptoms was 62 days (range 4-136 days), median duration of peripheral neuropathies was 256 days (range 2-465 days) including those with ongoing neuropathy.

周围神经病变：Cartitute-1中有6名患者发生了周围神经病变。这些神经病表现为感觉，运动或感觉运动神经病。症状发作的中位时间为62天（范围4-136天），周围神经病变的中位持续时间为256天 天（范围2-465天），包括持续神经病变的患者。

Patients who experienced peripheral neuropathy also experienced cranial nerve palsies or GBS in other ongoing trials of ciltacabtagene autoleucel. Monitor patients for signs and symptoms of peripheral neuropathies. .

在其他正在进行的ciltacabtagene autoleucel试验中，经历周围神经病变的患者也经历了颅神经麻痹或GBS。监测患者周围神经病变的体征和症状。

Cranial Nerve Palsies: Three patients (3.1%) experienced cranial nerve palsies in CARTITUDE-1. All three patients had 7th cranial nerve palsy; one patient had 5th cranial nerve palsy as well. Median time to onset was 26 days (range 21-101 days) following infusion of ciltacabtagene autoleucel. Occurrence of 3rd and 6th cranial nerve palsy, bilateral 7th cranial nerve palsy, worsening of cranial nerve palsy after improvement, and occurrence of peripheral neuropathy in patients with cranial nerve palsy have also been reported in ongoing trials of ciltacabtagene autoleucel.

颅神经麻痹：三名患者（3.1%）在Cartitute-1中出现颅神经麻痹。所有三名患者均患有第七颅神经麻痹；一名患者也有第五颅神经麻痹。输注ciltacabtagene autoleucel后，中位发病时间为26天（范围21-101天）。正在进行的西他卡布汀自体白血病试验也报道了第3和第6颅神经麻痹的发生，双侧第7颅神经麻痹，改善后颅神经麻痹的恶化以及颅神经麻痹患者周围神经病变的发生。

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. .

监测患者颅神经麻痹的体征和症状。根据体征和症状的严重程度和进展，考虑使用全身皮质类固醇进行治疗。

Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS): Fatal HLH occurred in one patient (1%), 99 days after ciltacabtagene autoleucel. The HLH event was preceded by prolonged CRS lasting 97 days. The manifestations of HLH/MAS include hypotension, hypoxia with diffuse alveolar damage, coagulopathy, cytopenia, and multi-organ dysfunction, including renal dysfunction. .

噬血细胞性淋巴组织细胞增生症（HLH）/巨噬细胞活化综合征（MAS）：一名患者（1%）在西他卡宾自体白血病后99天发生致命的HLH。HLH事件之前是持续97天的CRS延长。HLH/MAS的表现包括低血压，缺氧伴弥漫性肺泡损伤，凝血病，血细胞减少和多器官功能障碍，包括肾功能不全。

One patient with Grade 4 HLH/MAS developed fatal intracerebral and gastrointestinal hemorrhage in the setting of coagulopathy and thrombocytopenia 12 days after treatment in another ongoing study. Patients who develop HLH/MAS have an increased risk of severe bleeding. Monitor hematological parameters in patients with HLH/MAS and transfuse per institutional guidelines.  .

在另一项正在进行的研究中，一名4级HLH/MAS患者在治疗后12天出现凝血病和血小板减少症，导致致命的脑内和胃肠道出血。发生HLH/MAS的患者严重出血的风险增加。根据机构指南监测HLH/MAS患者的血液学参数和输血。

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.

HLH是一种危及生命的疾病，如果不及早发现和治疗，死亡率很高。HLH/MAS的治疗应按照机构标准进行。

CARVYKTI® REMS: Because of the risk of CRS and neurologic toxicities, CARVYKTI® is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI® REMS.

CARVYKTI®REMS：由于CRS和神经系统毒性的风险，CARVYKTI®只能通过风险评估和缓解策略（REMS）下的受限程序获得，称为CARVYKTI®REMS。

Further information is available at https://www.carvyktirems.com/ or 1-844-672-0067.

更多信息请访问https://www.carvyktirems.com/或1-844-672-0067。

Prolonged and Recurrent Cytopenias: Patients may exhibit prolonged and recurrent cytopenias following lymphodepleting chemotherapy and CARVYKTI® infusion. One patient underwent autologous stem cell therapy for hematopoietic reconstitution due to prolonged thrombocytopenia.

长期和复发性血细胞减少症：患者在淋巴清除化疗和CARVYKTI®输注后可能表现出长期和复发性血细胞减少症。由于血小板减少症延长，一名患者接受了自体干细胞治疗以进行造血重建。

In CARTITUDE-1, 30% (29/97) of patients experienced prolonged Grade 3 or 4 neutropenia and 41% (40/97) of patients experienced prolonged Grade 3 or 4 thrombocytopenia that had not resolved by Day 30 following ciltacabtagene autoleucel infusion.

在Cartitute-1中，30%（29/97）的患者经历了延长的3级或4级中性粒细胞减少症，41%（40/97）的患者经历了延长的3级或4级血小板减少症，这些患者在西他卡宾自体白血病输注后第30天尚未解决。

Recurrent Grade 3 or 4 neutropenia, thrombocytopenia, lymphopenia and anemia were seen in 63% (61/97), 18% (17/97), 60% (58/97), and 37% (36/97) after recovery from initial Grade 3 or 4 cytopenia following infusion. After Day 60 following ciltacabtagene autoleucel infusion, 31%, 12% and 6% of patients had a recurrence of Grade 3 or higher lymphopenia, neutropenia and thrombocytopenia, respectively, after initial recovery of their Grade 3 or 4 cytopenia.

输注后从初始3级或4级血细胞减少症恢复后，复发性3级或4级中性粒细胞减少症，血小板减少症，淋巴细胞减少症和贫血分别为63%（61/97），18%（17/97），60%（58/97）和37%（36/97）。在西他卡本自体白血病输注后第60天，在3级或4级血细胞减少症初步恢复后，分别有31%，12%和6%的患者复发3级或更高的淋巴细胞减少症，中性粒细胞减少症和血小板减少症。

Eighty-seven percent (84/97) 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. Six and 11 patients had Grade 3 or 4 neutropenia and thrombocytopenia, respectively, at the time of death. .

在3级或4级血细胞减少症初步恢复后，87%（84/97）的患者有一次，两次或三次或更多次3级或4级血细胞减少症复发。死亡时分别有6名和11名患者出现3级或4级中性粒细胞减少症和血小板减少症。

Monitor blood counts prior to and after CARVYKTI® infusion. Manage cytopenias with growth factors and blood product transfusion support according to local institutional guidelines.

在CARVYKTI®输注前后监测血细胞计数。根据当地机构指南，通过生长因子和血液制品输血支持管理血细胞减少症。

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.

感染：CARVYKTI®不应用于活动性感染或炎症性疾病患者。CARVYKTI®输注后患者发生严重，危及生命或致命的感染。

Infections (all grades) occurred in 57 (59%) patients. Grade 3 or 4 infections occurred in 23% (22/97) of patients; Grade 3 or 4 infections with an unspecified pathogen occurred in 17%, viral infections in 7%, bacterial infections in 1%, and fungal infections in 1% of patients. Overall, four patients had Grade 5 infections: lung abscess (n=1), sepsis (n=2) and pneumonia (n=1). .

57名（59%）患者发生感染（所有级别）。23%（22/97）的患者发生3或4级感染；未指定病原体的3或4级感染发生率为17%，病毒感染发生率为7%，细菌感染发生率为1%，真菌感染发生率为1%。总体而言，四名患者患有5级感染：肺脓肿（n=1），败血症（n=2）和肺炎（n=1）。

Grade 5 infections reported in other studies include bronchopulmonary aspergillosis, pneumocystis jirovecii pneumonia, and CMV colitis (with HSV-1 hepatitis). Another patient developed mycotic aneurysm due to cerebral aspergillosis and died of subarachnoid hemorrhage.

其他研究报道的5级感染包括支气管肺曲霉病，吉罗维肺孢子虫肺炎和CMV结肠炎（伴有HSV-1肝炎）。另一名患者因脑曲霉菌病发展为真菌性动脉瘤，死于蛛网膜下腔出血。

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 10% of patients after ciltacabtagene autoleucel infusion, and may be concurrent with CRS.

在CARVYKTI®输注前后监测患者的感染体征和症状，并对患者进行适当治疗。根据标准机构指南管理预防性，先发制人和/或治疗性抗菌药物。西他卡本自体白血病输注后，有10%的患者出现发热性中性粒细胞减少症，可能与CRS同时发生。

In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids and other supportive care, as medically indicated. .

在发热性中性粒细胞减少症的情况下，根据医学指示，评估感染并使用广谱抗生素，液体和其他支持治疗。

In a randomized controlled study of relapsed or refractory multiple myeloma (CARTITUDE-4), patients treated with ciltacabtagene autoleucel had an increased rate of fatal COVID-19 infections compared to the standard therapy arm. Counsel patients on the importance of prevention measures. Follow institutional guidelines for the vaccination and management of immunocompromised patients with COVID-19. .

在一项复发或难治性多发性骨髓瘤（Cartitute-4）的随机对照研究中，与标准治疗组相比，接受西他卡宾自体白血病治疗的患者致命性COVID-19感染率增加。就预防措施的重要性向患者提供咨询。遵循免疫功能低下的新型冠状病毒肺炎患者的疫苗接种和管理机构指南。

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.

病毒再激活：低丙种球蛋白血症患者可能发生乙型肝炎病毒（HBV）再激活，在某些情况下会导致暴发性肝炎，肝衰竭和死亡。在收集细胞进行生产之前，根据临床指南进行巨细胞病毒（CMV），乙型肝炎病毒（HBV），丙型肝炎病毒（HCV）和人类免疫缺陷病毒（HIV）或任何其他感染因子的筛查。

Consider antiviral therapy to prevent viral reactivation per local institutional guidelines/clinical practice. .

根据当地机构指南/临床实践，考虑抗病毒治疗以防止病毒再激活。

Hypogammaglobulinemia was reported as an adverse event in 12% (12/97) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 92% (89/97) of patients. 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. .

据报道，低丙种球蛋白血症是12%（12/97）患者的不良事件；92%（89/97）的患者输注后实验室IgG水平降至500 mg/dL以下。用CARVYKTI®治疗后监测免疫球蛋白水平，并给予IVIG治疗IgG <400 毫克/分升。按照当地机构指南管理，包括感染预防措施和抗生素或抗病毒预防措施。

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®. .

活疫苗的使用：尚未研究在CARVYKTI®治疗期间或之后用活病毒疫苗免疫的安全性。在开始淋巴清除化疗之前，在CARVYKTI®治疗期间以及在用CARVYKTI®治疗后免疫恢复之前，至少6周内不建议接种活病毒疫苗。

Hypersensitivity Reactions have occurred in 5% (5/97) of patients following ciltacabtagene autoleucel infusion. 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.

西他卡本自体白血病输注后，5%（5/97）的患者发生了超敏反应。严重的超敏反应，包括过敏反应，可能是由于CARVYKTI®中的二甲基亚砜（DMSO）。输注后应仔细监测患者2小时的严重反应体征和症状。

Treat promptly and manage appropriately according to the severity of the hypersensitivity reaction. .

根据过敏反应的严重程度及时治疗并适当管理。

Secondary Malignancies: Patients may develop secondary malignancies. Monitor life-long 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 for testing of secondary malignancy of T cell origin. .

继发性恶性肿瘤：患者可能发展为继发性恶性肿瘤。终身监测继发性恶性肿瘤。如果发生继发性恶性肿瘤，请联系Janssen Biotech，Inc.，电话1-800-526-7736进行报告，并获取有关收集患者样本以检测T细胞来源继发性恶性肿瘤的说明。

Effects on Ability to Drive and Use Machines: Due to the potential for neurologic events, including altered mental status, seizures, neurocognitive decline, or neuropathy, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following CARVYKTI® infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery during this initial period, and in the event of new onset of any neurologic toxicities. .

对驾驶和使用机器能力的影响：由于可能发生神经系统事件，包括精神状态改变，癫痫发作，神经认知能力下降或神经病，患者在输注CARVYKTI®后8周内有意识或协调能力改变或下降的风险。建议患者不要驾驶和从事危险的职业或活动，例如在此初始阶段以及在新出现任何神经系统毒性的情况下操作重型或潜在危险的机器。

ADVERSE REACTIONS

不良反应

The most common non-laboratory adverse reactions (incidence greater than 20%) are pyrexia, cytokine release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections of unspecified pathogen, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting.

最常见的非实验室不良反应（发生率大于20%）是发热，细胞因子释放综合征，低丙种球蛋白血症，低血压，肌肉骨骼疼痛，疲劳，不明病原体感染，咳嗽，寒战，腹泻，恶心，脑病，食欲下降，上呼吸道感染，头痛，心动过速，头晕，呼吸困难，水肿，病毒感染，凝血病，便秘和呕吐。

The most common laboratory adverse reactions (incidence greater than or equal to 50%) include thrombocytopenia, neutropenia, anemia, aminotransferase elevation, and hypoalbuminemia. .

最常见的实验室不良反应（发生率大于或等于50%）包括血小板减少症，中性粒细胞减少症，贫血，转氨酶升高和低白蛋白血症。

Please read full Prescribing Information, including Boxed Warning, for CARVYKTI®.

请阅读CARVYKTI®的完整处方信息，包括盒装警告。

About Johnson & Johnson

关于强生公司

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.

在强生公司，我们相信健康就是一切。我们在医疗保健创新方面的优势使我们能够建立一个预防、治疗和治愈复杂疾病的世界，在这个世界上，治疗更加智能，侵入性更小，解决方案更加个性化。通过我们在创新医学和医学技术方面的专业知识，我们拥有独特的优势，可以在今天的所有医疗保健解决方案中进行创新，以实现明天的突破，并深刻影响人类的健康。

Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc. are both Johnson & Johnson companies..

了解更多信息，请访问https://www.jnj.com/或访问www.janssen.com/johnson-johnson-innovative-medicine。请访问@JanssenUS和@JNJInnovMed。Janssen Research&Development，LLC和Janssen Biotech，Inc.都是强生公司。