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.

Transient acute kidney injury after chimeric antigen receptor T-cell therapy in patients with hematological malignancies

“…Our analysis also suggests that there were no differences in AKI development between standard and dose-reduced fludarabine after the multivariable analysis in accordance with Wood et al. [ 48 ].…”

Expanding the role of CAR T‐cell therapy: From B‐cell hematological malignancies to autoimmune rheumatic diseases

“…Among these are their on-target/off-tumor toxicity, tumor lysis syndrome (TLS), CRS, CRS-related coagulopathy, hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS), CAR T-cell-related encephalopathy syndrome (CRES) or ICANS, acute kidney injury (AKI), infections, cytopenia, anaphylaxis, which may lead to multi-organ failure. [70][71][72][73] We also have to expect some adverse effects when applying CAR T-cell therapy in rheumatology practice. 55,74 CRS is the most common side effect of CAR T-cell therapies.…”

“…Although CAR T‐cells are a revolutionary therapeutic approach in some refractory B‐cell diseases, severe or even life‐threatening adverse events are related to their use in clinical practice. Among these are their on‐target/off‐tumor toxicity, tumor lysis syndrome (TLS), CRS, CRS‐related coagulopathy, hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS), CAR T‐cell‐related encephalopathy syndrome (CRES) or ICANS, acute kidney injury (AKI), infections, cytopenia, anaphylaxis, which may lead to multi‐organ failure 70–73 . We also have to expect some adverse effects when applying CAR T‐cell therapy in rheumatology practice 55,74 …”

“…One important aspect when treating patients with CAR T‐cells is the possibility of the development of AKI. Possible pathophysiological mechanisms include hypotension, increased vascular permeability, intravascular depletion, and cardiac toxicity in the course of CRS, TLS, HLH, inflammatory cytokines, which alone or together with factors such as the lymphodepletion therapy, the effect of nephrotoxic agents and the dehydration promote pre‐renal or deteriorates a pre‐existing AKI 72 . This could also be applied to patients with renal insufficiency caused by autoimmune rheumatic disease.…”

“…72 This could also be applied to patients with renal insufficiency caused by autoimmune rheumatic disease. T-cell therapy, respectively.…”