#5213 RELATIONSHIP BETWEEN CYTOKINE RELEASE SYNDROME AND ACUTE KIDNEY INJURY AFTER CHIMERIC ANTIGEN RECEPTOR T CELL THERAPY IN HEMATOLOGIC NEOPLASMS

Abstract

Abstract Background and Aims CAR-T cell therapy is a promising new immunotherapy to treat refractory hematologic malignancies (RHM). Despite the potential benefits, high rates of treatment related toxicity have been reported after CAR-T infusion. AKI occurs between 20-30% after treatment. The purpose of this study was to identify the relationship between the proinflammatory status (CRS, ICANs, and febrile neutropenia) and AKI development. Method Medical records of 115 patients treated with CD19-targeted CAR-T cells for refractory hematologic malignancies at HUVH between July 2018 and May 2021 were reviewed. Clinical data was reviewed within 30 days after CAR-T cells therapy. AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria: grade 1, 1.5 to <2-fold of baseline; grade 2, 2- to <3-fold of baseline; grade 3, ≥3-fold of baseline We performed statistically analysis to identify risk factors for AKI development. Results A total of 24/115 patients presented AKI after CAR-T infusion. AKI Akin stage 1 was diagnosed in 17 (15%) patients, AKI Akin stage 2 was diagnosed in 4 (3.5%) patients, and AKI Akin stage 3 was diagnosed in 3 (2.6%) patients. 4/17 patients died in the AKI Akin stage 1 group while 2/3 patients in the AKI Akin stage 3 group. Renal function was recovered in 19/24 (79%) patients within the first month. Chronic kidney disease was present in 13% patients. Among types of CAR-T cell infusion, “investigational product” was infused in 27.8%, tisagenlecleucel in 49.6%, axicabtagen ciloleucelin in 20%, and brexucabtagene autoleucel in 2.6%. The most frequent complications were cytokine release syndrome (81.9%), febrile neutropenia (67%) and neurotoxicity (28.7%). Tocilizumab was given in 31 (27%) patients for CRS grade ≥2, and 5% of patients were admitted to the intensive care unit 3/36 patients died after CAR-T infusion. Male sex, CAR T-cell construct, ICANs, CRS, and death by any cause were associated with AKI. Only CRS ≥2(p=0.001) was identified as independent risk factor for AKI. Conclusion AKI development is mainly transient and associated with the proinflammatory status after CAR-T cell infusion.