Chimeric Antigen Receptor (CAR) T cells targeting CD19 induce durable remissions in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), but many patients experience treatmentrelated toxicity. Cytokine release syndrome and immune effector cell-associated neurologic syndrome are extensively characterized. However, limited data exist on the burden, predictors, and implications of acute kidney injury (AKI) after CAR T cell therapy. On initial screening of the FDA adverse event reporting system, we identified a disproportionately high rate of renal adverse events among nearly 6,000 CAR T adverse event reports, suggesting it is clinically important in this patient population. In a subsequent single-center analysis of 399 NHL patients treated with CD19 CAR T cells, we found a substantial burden of AKI after CAR T infusion (10% and 5% of any grade and grade ≥2 AKI) with pre-renal causes being predominant (72%). Evolution to chronic kidney disease was rare, however, 3 patients required hemodialysis. Importantly, patients experiencing cytokine release syndrome and/or neurotoxicity as well as those with low serum albumin and high inflammatory cytokines, including IL-6 and TNF-alpha, were more likely to develop AKI. While pre-CAR T renal dysfunction was not associated with adverse outcomes, patients developing post-CAR T AKI had lower overall survival compared to their counterparts. Our findings indicate that renal dysfunction is a common toxicity of CAR T cell therapy with meaningful prognostic impact. Notably, the link between systemic inflammation and renal dysfunction, suggests that readily available biomarkers may inform on renal injury risk after CAR T cell therapy.

中文翻译：

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CD19 嵌合抗原受体 T 细胞治疗后肾损伤的预测因素和影响。


靶向 CD19 的嵌合抗原受体 （CAR） T 细胞在复发或难治性非霍奇金淋巴瘤 （NHL） 患者中诱导持久缓解，但许多患者会出现与治疗相关的毒性。细胞因子释放综合征和免疫效应细胞相关神经综合征具有广泛的特征。然而，关于 CAR T 细胞治疗后急性肾损伤 （AKI） 的负担、预测因素和影响的数据有限。在对 FDA 不良事件报告系统的初步筛选中，我们在近 6,000 份 CAR T 不良事件报告中发现肾脏不良事件发生率不成比例地高，这表明它在这一患者群体中具有临床重要性。在随后对 399 名接受 CD19 CAR T 细胞治疗的 NHL 患者的单中心分析中，我们发现 CAR T 输注后 AKI 负担沉重 （任何级别和 5% 和 2 级 ≥2 AKI），其中肾前性原因占主导地位 （72%）。进展为慢性肾病的情况很少见，但 3 例患者需要血液透析。重要的是，出现细胞因子释放综合征和/或神经毒性的患者以及低血清白蛋白和高炎性细胞因子（包括 IL-6 和 TNF-α）的患者更容易发生 AKI。虽然 CAR T 前肾功能不全与不良结局无关，但与 CAR T AKI 后患者相比，发生 CAR T AKI 的患者总生存期较低。我们的研究结果表明，肾功能不全是 CAR T 细胞疗法的常见毒性，具有有意义的预后影响。值得注意的是，全身炎症与肾功能不全之间的联系表明，现成的生物标志物可能告知 CAR T 细胞治疗后的肾损伤风险。