Gligorevic Strahinja, Brezic Nebojsa, Jagodzinski Joshua, Radulovic Andjela, Peranovic Aleksandar, Dumic Igor
Internal Medicine Residency Program, North Central Bronx Hospital, Bronx, NY 10467, USA.
Internal Medicine Residency Program (Preliminary Track), Lincoln Medical and Mental Health Center, Bronx, NY 10467, USA.
J Clin Med. 2025 Jul 3;14(13):4723. doi: 10.3390/jcm14134723.
Cytokine release syndrome (CRS) is a life-threatening systemic inflammatory condition marked by excessive cytokine production, leading to multi-organ dysfunction. It is commonly associated with T-cell-engaging therapies such as chimeric antigen receptor (CAR) T cells, T-cell receptor bispecific molecules, and monoclonal antibodies. Carfilzomib, a proteasome inhibitor, is known to cause a range of adverse effects, primarily hematologic and cardiovascular. However, multiorgan failure grade 5 (fatal), resembling CRS has not been previously reported in association with Carfilzomib. : A 74-year-old male with relapsed multiple myeloma developed grade 5 multiorgan failure 60 min after the third dose of Carfilzomib, resulting in death within 24 h of symptom onset. The patient tolerated the first doses of Carfilzomib well with only fever and headache developing post infusion. Before the second dose, the patient developed worsening pancytopenia, prompting the discontinuation of Lenalidomide. After the second Carfilzomib infusion, he experienced fever and transient encephalopathy, which resolved with acetaminophen, corticosteroids, and supportive care. However, following the third dose, he rapidly deteriorated-developing fever, tachycardia, hypotension, hypoxia, and encephalopathy. Despite aggressive management with intravenous fluids, broad-spectrum antibiotics, corticosteroids, and tocilizumab, the patient progressed to refractory shock and multi-organ failure, culminating in death within 24 h. A comprehensive infectious workup was negative, ruling out sepsis and suggesting possible Carfilzomib-induced CRS. Grade 5 multiorgan failure with signs and symptoms similar with CRS following Carfilzomib administration is a rare but potentially fatal adverse drug reaction. Further research is needed to better define the risk factors and optimal management strategies for Carfilzomib-induced multiorgan failure and possible CRS.
细胞因子释放综合征（CRS）是一种危及生命的全身性炎症性疾病，其特征是细胞因子过度产生，导致多器官功能障碍。它通常与嵌合抗原受体（CAR）T细胞、T细胞受体双特异性分子和单克隆抗体等T细胞靶向疗法相关。蛋白酶体抑制剂卡非佐米已知会引起一系列不良反应，主要是血液学和心血管方面的。然而，此前尚未有与卡非佐米相关的5级多器官衰竭（致命）的报道，其症状类似于CRS。：一名74岁复发性多发性骨髓瘤男性患者在第三次注射卡非佐米后60分钟出现5级多器官衰竭，症状出现后24小时内死亡。患者对卡非佐米的前几剂耐受性良好，仅在输注后出现发热和头痛。在第二次给药前，患者全血细胞减少症加重，促使停用来那度胺。第二次卡非佐米输注后，他出现发热和短暂性脑病，通过对乙酰氨基酚、皮质类固醇和支持性治疗得以缓解。然而，在第三次给药后，他迅速恶化，出现发热、心动过速、低血压、缺氧和脑病。尽管采取了积极的治疗措施，包括静脉输液、广谱抗生素、皮质类固醇和托珠单抗，但患者仍进展为难治性休克和多器官衰竭，最终在24小时内死亡。全面的感染检查结果为阴性，排除了败血症，提示可能是卡非佐米诱导的CRS。卡非佐米给药后出现的5级多器官衰竭，其体征和症状与CRS相似，是一种罕见但可能致命的药物不良反应。需要进一步研究以更好地确定卡非佐米诱导的多器官衰竭和可能的CRS的危险因素及最佳管理策略。
