| アブストラクト | 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. |
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| 投稿者 | Boardman, Alexander P; Gutgarts, Victoria; Flynn, Jessica; Devlin, Sean M; Goldman, Adam; Tomas, Ana Alarcon; Fein, Joshua A; Slingerland, John B; Parascondola, Allison; Lin, Richard J; Scordo, Michael; Dahi, Parastoo B; Giralt, Sergio; Palomba, M Lia; Salles, Gilles; Nath, Karthik; Walji, Moneeza; Corona, Magdalena; Park, Jae H; Shah, Gunjan L; Perales, Miguel-Angel; Jaffer-Sathick, Insara; Shouval, Roni |
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| 組織名 | Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center,;New York, NY; Cellular Therapy Service, Department of Medicine, Memorial Sloan;Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell;Medical College, New York.;Department of Medicine, Weill Cornell Medical College, New York, NY; Renal;Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New;York.;Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer;Center, New York.;Department of Medicine, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School;of Medicine, Aviv University, Israel.;Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan;Kettering Cancer Center, New York, NY; Hematology and Hemotherapy Service,;Hospital Universitario Gregorio Maranon, Madrid, Spain.;Department of Medicine, Weill Cornell Medical College, New York.;Kettering Cancer Center, New York.;Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer;Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New;York, NY; Adult Bone Marrow Transplant Service, Department of Medicine, Memorial;Sloan Kettering Cancer Center, New York.;Department of Medicine, Weill Cornell Medical College, New York, NY; Adult Bone;Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering;Cancer Center, New York.;Hematology and Hemotherapy Service, Hospital Universitario Ramon y Cajal, Madrid,;Spain.;Sloan Kettering Cancer Center, New York, NY; Department of Bone Marrow;Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of;Medicine, Aviv University, Israel. shouvalr@mskcc.org. |
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