Acute Kidney Injury and Electrolyte Abnormalities After Chimeric Antigen Receptor T-Cell (CAR-T) Therapy for Diffuse Large B-Cell Lymphoma

医学 细胞因子释放综合征 急性肾损伤 低钾血症 内科学 嵌合抗原受体 胃肠病学 癌症 外科 免疫疗法
作者
Shruti Gupta,Harish Seethapathy,Ian A. Strohbehn,Matthew J. Frigault,Elizabeth O’Donnell,Caron A. Jacobson,Shveta S. Motwani,Samir M. Parikh,Gary C. Curhan,Kerry L. Reynolds,David E. Leaf,Meghan E. Sise
出处
期刊:American Journal of Kidney Diseases [Elsevier BV]
卷期号:76 (1): 63-71 被引量:97
标识
DOI:10.1053/j.ajkd.2019.10.011
摘要

Rationale & Objective Cytokine release syndrome is a well-known complication of chimeric antigen receptor T-cell (CAR-T) therapy and can lead to multiorgan dysfunction. However, the nephrotoxicity of CAR-T therapy is unknown. We aimed to characterize the occurrence, cause, and outcomes of acute kidney injury (AKI), along with the occurrence of electrolyte abnormalities, among adults with diffuse large B-cell lymphoma receiving CAR-T therapy. Study Design Case series. Setting & Participants We reviewed the course of 78 adults receiving CAR-T therapy with axicabtagene ciloleucel or tisagenlecleucel at 2 major cancer centers between October 2017 and February 2019. Baseline demographics, comorbid conditions, medications, and laboratory values were obtained from electronic health records. AKI was defined using KDIGO (Kidney Disease: Improving Global Outcomes) criteria. The cause, clinical course, and outcome of AKI events and electrolyte abnormalities in the first 30 days after CAR-T infusion were characterized using data contained in electronic health records. Results Among 78 patients receiving CAR-T therapy, cytokine release syndrome occurred in 85%, of whom 62% were treated with tocilizumab. AKI occurred in 15 patients (19%): 8 had decreased kidney perfusion, 6 developed acute tubular necrosis, and 1 patient had urinary obstruction related to disease progression. Those with acute tubular necrosis and obstruction had the longest lengths of stay and highest 60-day mortality. Electrolyte abnormalities were common; hypophosphatemia, hypokalemia, and hyponatremia occurred in 75%, 56%, and 51% of patients, respectively. Limitations Small sample size; AKI adjudicated by retrospective chart review; lack of biopsy data. Conclusions In this case series of patients with diffuse large B-cell lymphoma receiving CAR-T therapy, AKI and electrolyte abnormalities occurred commonly in the context of cytokine release syndrome. Cytokine release syndrome is a well-known complication of chimeric antigen receptor T-cell (CAR-T) therapy and can lead to multiorgan dysfunction. However, the nephrotoxicity of CAR-T therapy is unknown. We aimed to characterize the occurrence, cause, and outcomes of acute kidney injury (AKI), along with the occurrence of electrolyte abnormalities, among adults with diffuse large B-cell lymphoma receiving CAR-T therapy. Case series. We reviewed the course of 78 adults receiving CAR-T therapy with axicabtagene ciloleucel or tisagenlecleucel at 2 major cancer centers between October 2017 and February 2019. Baseline demographics, comorbid conditions, medications, and laboratory values were obtained from electronic health records. AKI was defined using KDIGO (Kidney Disease: Improving Global Outcomes) criteria. The cause, clinical course, and outcome of AKI events and electrolyte abnormalities in the first 30 days after CAR-T infusion were characterized using data contained in electronic health records. Among 78 patients receiving CAR-T therapy, cytokine release syndrome occurred in 85%, of whom 62% were treated with tocilizumab. AKI occurred in 15 patients (19%): 8 had decreased kidney perfusion, 6 developed acute tubular necrosis, and 1 patient had urinary obstruction related to disease progression. Those with acute tubular necrosis and obstruction had the longest lengths of stay and highest 60-day mortality. Electrolyte abnormalities were common; hypophosphatemia, hypokalemia, and hyponatremia occurred in 75%, 56%, and 51% of patients, respectively. Small sample size; AKI adjudicated by retrospective chart review; lack of biopsy data. In this case series of patients with diffuse large B-cell lymphoma receiving CAR-T therapy, AKI and electrolyte abnormalities occurred commonly in the context of cytokine release syndrome.
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