Predictors and implications of renal injury after CD19 chimeric antigen receptor T-cell therapy
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 extensiv...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Ferrata Storti Foundation
2024-11-01
|
| Series: | Haematologica |
| Online Access: | https://haematologica.org/article/view/11835 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846160807511982080 |
|---|---|
| author | Alexander P. Boardman Victoria Gutgarts Jessica Flynn Sean M. Devlin Adam Goldman Ana Alarcon Tomas Joshua A. Fein John B. Slingerland Allison Parascondola Richard J. Lin Michael Scordo Parastoo B. Dahi Sergio Giralt M. Lia Palomba Gilles Salles Karthik Nath Moneeza Walji Magdalena Corona Jae H. Park Gunjan L. Shah Miguel-Angel Perales Insara Jaffer-Sathick Roni Shouval |
| author_facet | Alexander P. Boardman Victoria Gutgarts Jessica Flynn Sean M. Devlin Adam Goldman Ana Alarcon Tomas Joshua A. Fein John B. Slingerland Allison Parascondola Richard J. Lin Michael Scordo Parastoo B. Dahi Sergio Giralt M. Lia Palomba Gilles Salles Karthik Nath Moneeza Walji Magdalena Corona Jae H. Park Gunjan L. Shah Miguel-Angel Perales Insara Jaffer-Sathick Roni Shouval |
| author_sort | Alexander P. Boardman |
| collection | DOAJ |
| description |
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.
|
| format | Article |
| id | doaj-art-ea14faf0d5654d7e85d711bcd95f0978 |
| institution | Kabale University |
| issn | 0390-6078 1592-8721 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Ferrata Storti Foundation |
| record_format | Article |
| series | Haematologica |
| spelling | doaj-art-ea14faf0d5654d7e85d711bcd95f09782024-11-21T19:41:34ZengFerrata Storti FoundationHaematologica0390-60781592-87212024-11-01999110.3324/haematol.2024.286021Predictors and implications of renal injury after CD19 chimeric antigen receptor T-cell therapyAlexander P. Boardman0Victoria Gutgarts1Jessica Flynn2Sean M. Devlin3Adam Goldman4Ana Alarcon Tomas5Joshua A. Fein6John B. Slingerland7Allison Parascondola8Richard J. Lin9Michael Scordo10Parastoo B. Dahi11Sergio Giralt12M. Lia Palomba13Gilles Salles14Karthik Nath15Moneeza Walji16Magdalena Corona17Jae H. Park18Gunjan L. Shah19Miguel-Angel Perales20Insara Jaffer-Sathick21Roni Shouval22Lymphoma 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 YorkDepartment of Medicine, Weill Cornell Medical College, New York, NY; Renal Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New YorkDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New YorkDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New YorkDepartment of Medicine, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Aviv University, IsraelAdult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Hematology and Hemotherapy Service, Hospital Universitario Gregorio Marañón, Madrid, SpainDepartment of Medicine, Weill Cornell Medical College, New York, NYAdult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New YorkAdult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New YorkCellular 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 YorkCellular 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 YorkCellular 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 YorkCellular 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 YorkLymphoma 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 YorkLymphoma 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 YorkCellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New YorkDepartment of Medicine, Weill Cornell Medical College, New York, NY; Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New YorkHematology and Hemotherapy Service, Hospital Universitario Ramón y Cajal, Madrid, SpainCellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New YorkCellular 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 YorkCellular 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 YorkDepartment of Medicine, Weill Cornell Medical College, New York, NY; Renal Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New YorkCellular 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, NY; Department of Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Aviv University, Israel 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. https://haematologica.org/article/view/11835 |
| spellingShingle | Alexander P. Boardman Victoria Gutgarts Jessica Flynn Sean M. Devlin Adam Goldman Ana Alarcon Tomas Joshua A. Fein John B. Slingerland Allison Parascondola Richard J. Lin Michael Scordo Parastoo B. Dahi Sergio Giralt M. Lia Palomba Gilles Salles Karthik Nath Moneeza Walji Magdalena Corona Jae H. Park Gunjan L. Shah Miguel-Angel Perales Insara Jaffer-Sathick Roni Shouval Predictors and implications of renal injury after CD19 chimeric antigen receptor T-cell therapy Haematologica |
| title | Predictors and implications of renal injury after CD19 chimeric antigen receptor T-cell therapy |
| title_full | Predictors and implications of renal injury after CD19 chimeric antigen receptor T-cell therapy |
| title_fullStr | Predictors and implications of renal injury after CD19 chimeric antigen receptor T-cell therapy |
| title_full_unstemmed | Predictors and implications of renal injury after CD19 chimeric antigen receptor T-cell therapy |
| title_short | Predictors and implications of renal injury after CD19 chimeric antigen receptor T-cell therapy |
| title_sort | predictors and implications of renal injury after cd19 chimeric antigen receptor t cell therapy |
| url | https://haematologica.org/article/view/11835 |
| work_keys_str_mv | AT alexanderpboardman predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT victoriagutgarts predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT jessicaflynn predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT seanmdevlin predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT adamgoldman predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT anaalarcontomas predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT joshuaafein predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT johnbslingerland predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT allisonparascondola predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT richardjlin predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT michaelscordo predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT parastoobdahi predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT sergiogiralt predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT mliapalomba predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT gillessalles predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT karthiknath predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT moneezawalji predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT magdalenacorona predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT jaehpark predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT gunjanlshah predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT miguelangelperales predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT insarajaffersathick predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy AT ronishouval predictorsandimplicationsofrenalinjuryaftercd19chimericantigenreceptortcelltherapy |