FC072: Acute Kidney Injury and Chimeric Antigen Receptor (CAR)-T Therapy in Haematologic Neoplasias: The Importance of Kidney Disease
Authors: León Román Juan , Iacoboni Gloria , Bermejo Garcia Sheila , Carpio Cecilia , Bolufer Cardona Mónica , Bestard Oriol , Barba Pere , Jose Soler Romeo Maria 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Chimeric Antigen Receptor (CAR)-T cell therapy has been a revolutionary treatment for hematological malignancies. Additionally, its potential use in solid tumors such as ovarian, prostate and lung neoplasms is currently being investigated with promising results (1).
The most frequent complications after CAR T-cell therapy include cytokine release syndrome (CRS), neurotoxicity, infections, cytopenia and hypogammaglobulinaemia (2, 3, 4, 5). Acute kidney injury (AKI) occurs between 20–30%, mostly associated with cytokine release syndrome (CRS), hydroelectrolyte disorders and tumor lysis syndrome (TLS). The purpose of this study was to determine the demographics, laboratory results and clinical evolution of patients who have received CAR-T cell therapy to identify risk factors associated with AKI and long-term outcomes in these patients.

METHOD
We performed a retrospective review of the medical records of 115 patients with haematological neoplasms who received CD19-targeted CAR T-cell therapy at Vall d'Hebron Hospital between July 2018 and May 2021. Clinical and laboratory results of the first 60 days post-infusion were systematically examined and data was collected at the following days: +1, +7, +14, +21, +28 and +60. AKI was defined as the Kidney Disease Improving Global Outcomes (KDIGO) criteria: grade 1, 1.5 to &lt;2-fold of baseline; grade 2, 2 to &lt; 3-fold of baseline; and grade 3, ≥3-fold of baseline. Firstly, the sample was divided into two groups: patients with kidney injury and those without in order to identify risk factors for AKI. Secondly, actuarial survival curves were estimated using the Kaplan–Meier method.

RESULTS
A total of 24 (20.9%) of the 115 patients presented AKI after CAR-T cell therapy infusion. AKI was diagnosed by day +1 post-infusion in 3 (2.6%) patients, by day +7 in 13 (11.3%) patients, by day +14 in 1 (0.9%) patient, by day +21 in 2 (1.7%) patients, by day +28 in 2 patients (1.7%), by day +60 in 1 (0.9%) patient and 2 (1.7%) patients during the fludarabine and cyclophosphamide conditioning chemotherapy. Nineteen (79.2%) patients recovered kidney function within the first month after CAR-T infusion. Mean age was 61 ±14.8 years and 66.1% were male. Demographic and clinical characteristics are shown in Table 1 (AKI patients and non-AKI patients). Briefly, hypertension was present in 37.4% of patients, diabetes in 7.8%, chronic kidney disease in 13.9% and cardiovascular disease in 5.2%. Haematological neoplasms include diffuse large B-cell lymphoma (90.5%), B-cell acute lymphoblastic leukemia (5.2%), mantle lymphoma (3.5%) and primary mediastinal large B-cell lymphoma (0.68%). Among the types of CAR-T cell therapy, patients received tisagenlecleucel (49.6%), investigational products (27.8%), axicabtagen ciloleucelin (20%) and brexucabtagene autoleucel (2.6%). The most frequent complications were CRS (72.2%), febrile neutropenia (67%) and neurotoxicity (16.5%). Thirty-one (27%) patients required tocilizumab for CRS grade ≥ 2. A total of 5.2% of patients were admitted to the intensive care unit and 31.3% died. In the bivariate analysis, male sex, types of CAR-T cell therapy infused, and neurotoxicity were associated with AKI. Only male sex (1.26–21.9; P 0.23) and neurotoxicity (2.15–70.6; P 0.005) were identified as risk factors for AKI in multivariable analysis. In the actuarial survival analysis, levels of hemoglobin, creatinine, sodium and reactive C protein in day + 1 and in day +28 showed no statistically significant differences for mortality (Table 2).

CONCLUSION
CAR-T cell therapy has shown beneficial results in haematologic malignancies. In our study, 20.9% of patients developed AKI, especially in the first week of the CAR-T infusion. The majority of patients, a total of 79.2% of patients recovered kidney function within the first 28 days post-treatment, suggesting that AKI is a frequent but mild disease with a fast recovery in patients treated with CAR-T cells.