Safety of CAR-T Cell Therapy in Patients With Renal Failure/Acute Kidney Injury: Focused Review.

ABSTRACT

Chimeric antigen receptor (CAR) T-cell therapy is novel immunotherapy targeting specifically cancerous cells, and has been shown to induce durable remissions in some refractory hematological malignancies. However, CAR T-cell therapy has adverse effects, such as cytokine release syndrome (CRS), immune effector-associated neurotoxicity syndrome (ICANS), tumor lysis syndrome (TLS), and acute kidney injury (AKI), among others. Not many studies have covered the repercussions of CAR T-cell therapy on the kidneys. In this review, we summarized the available evidence on the safety profile of CAR T-cell therapy in patients with pre-existing renal insufficiency/AKI and in those who develop AKI as a result of CAR T-cell therapy. With a 30% incidence of AKI post-CAR T-cell, various pathophysiological mechanisms, such as CRS, hemophagocytic lymphohistiocytosis (HLH), TLS, serum cytokines, and inflammatory biomarkers, have been shown to play a role. However, CRS is commonly reported as an underlying mechanism. Overall, 18% of patients in our included studies developed AKI after receiving CAR T-cell therapy, and most cases were reversible with appropriate therapy. While phase-1 clinical trials exclude patients with significant renal toxicity, two studies (Mamlouk et al. and Hunter et al.) reported successful treatment of dialysis-dependent patients with refractory diffuse large B-cell lymphoma, and demonstrated that CAR T-cell therapy and lymphodepletion (Flu/Cy) can be safely administered.