TY - JOUR
T1 - Acute Kidney Injury after CAR-T Cell Therapy
T2 - Low Incidence and Rapid Recovery
AU - Gutgarts, Victoria
AU - Jain, Tania
AU - Zheng, Junting
AU - Maloy, Molly A.
AU - Ruiz, Josel D.
AU - Pennisi, Martina
AU - Jaimes, Edgar A.
AU - Perales, Miguel Angel
AU - Sathick, Jaffer
N1 - Funding Information:
Financial disclosure: This research was supported in part by National Institutes of Health Grant P01 CA23766 (to M.A.P.) and National Cancer Institute Cancer Center Support Grant P30 CA008748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Conflict of interest statement: M.-A.P. reports honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda. He serves on data and safety monitoring boards for for Cidara Therapeutics, Servier, and Medigene and on scientific advisory boards of MolMed and NexImmune. He has received research support for clinical trials from Incyte, Kite/Gilead, and Miltenyi Biotec. He serves in a volunteer capacity as a member of the Board of Directors of American Society for Transplantation and Cellular Therapy and Be The Match (National Marrow Donor Program), as well as on the Center for International Blood & Marrow Transplant Research Cellular Immunotherapy Data Resource Committee. E.A.J. is Chief Medical Officer, a shareholder, and a cofounder of Goldilocks Therapeutics. T.J. is a consultant for Takeda Oncology. The other authors have no other relevant conflicts of interest to declare. Financial disclosure: See Acknowledgments on page 1076.
Funding Information:
Financial disclosure: This research was supported in part by National Institutes of Health Grant P01 CA23766 (to M.A.P.) and National Cancer Institute Cancer Center Support Grant P30 CA008748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health .
Publisher Copyright:
© 2020 American Society for Transplantation and Cellular Therapy
PY - 2020/6
Y1 - 2020/6
N2 - Chimeric antigen receptor (CAR) T cell therapy using engineered cytotoxic T cells has shown promising responses in various hematologic malignancies. Cytokine release syndrome (CRS) and immune effector cell-associated neurologic syndrome (ICANS) are recognized toxicities of CAR-T, whereas kidney injury remains less well recognized. The objective of the present study was to identify the incidence of acute kidney injury (AKI) after CAR-T cell therapy, potential risk factors, and recovery of kidney function. We performed a retrospective review of 46 adult patients with non-Hodgkin lymphoma treated with CAR-T therapy between February 2018 and February 2019 at our institution. Serum creatinine values before CAR-T therapy through day 100 were used to assess AKI, as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria: grade 1, 1.5- to <2-fold of baseline; grade 2, 2- to <3-fold of baseline; grade 3, ≥3-fold of baseline. CRS and ICANS were graded using the consensus criteria of the American Society of Transplantation and Cellular Therapy. The overall incidence of CRS was 78.3% (95% confidence interval [CI], 66% to 90.5%), of whom 13% (95% CI, 3.3% to 22.8%) developed grade 3-4 CRS, whereas the overall incidence of ICANS was lower at 45.7% (95% CI, 3.1% to 60.3%). The cumulative incidence of any grade AKI by day 100 was 30% (95% CI, 16.9% to 43.9%), with a grade 1 AKI incidence of 21.7% (95% CI, 9.7% to 33.8%) and a grade 2-3 AKI incidence of 8.7% (95% CI,. 4% to 17%). No patients developed severe AKI necessitating renal replacement therapy. Patients with previous autologous or allogeneic stem cell transplantation, those requiring intensive care unit level care and with grade 3-4 CRS had a higher incidence of AKI. Most patients recovered, with kidney function returning to baseline within 30 days. We conclude that with early recognition and management of CAR-T complications, the incidence of AKI is low, the severity of injury is mild, and most patients recover kidney function within 30 days.
AB - Chimeric antigen receptor (CAR) T cell therapy using engineered cytotoxic T cells has shown promising responses in various hematologic malignancies. Cytokine release syndrome (CRS) and immune effector cell-associated neurologic syndrome (ICANS) are recognized toxicities of CAR-T, whereas kidney injury remains less well recognized. The objective of the present study was to identify the incidence of acute kidney injury (AKI) after CAR-T cell therapy, potential risk factors, and recovery of kidney function. We performed a retrospective review of 46 adult patients with non-Hodgkin lymphoma treated with CAR-T therapy between February 2018 and February 2019 at our institution. Serum creatinine values before CAR-T therapy through day 100 were used to assess AKI, as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria: grade 1, 1.5- to <2-fold of baseline; grade 2, 2- to <3-fold of baseline; grade 3, ≥3-fold of baseline. CRS and ICANS were graded using the consensus criteria of the American Society of Transplantation and Cellular Therapy. The overall incidence of CRS was 78.3% (95% confidence interval [CI], 66% to 90.5%), of whom 13% (95% CI, 3.3% to 22.8%) developed grade 3-4 CRS, whereas the overall incidence of ICANS was lower at 45.7% (95% CI, 3.1% to 60.3%). The cumulative incidence of any grade AKI by day 100 was 30% (95% CI, 16.9% to 43.9%), with a grade 1 AKI incidence of 21.7% (95% CI, 9.7% to 33.8%) and a grade 2-3 AKI incidence of 8.7% (95% CI,. 4% to 17%). No patients developed severe AKI necessitating renal replacement therapy. Patients with previous autologous or allogeneic stem cell transplantation, those requiring intensive care unit level care and with grade 3-4 CRS had a higher incidence of AKI. Most patients recovered, with kidney function returning to baseline within 30 days. We conclude that with early recognition and management of CAR-T complications, the incidence of AKI is low, the severity of injury is mild, and most patients recover kidney function within 30 days.
KW - Acute kidney impairment
KW - Chimeric antigen receptor T cell therapy
KW - Toxicity
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U2 - 10.1016/j.bbmt.2020.02.012
DO - 10.1016/j.bbmt.2020.02.012
M3 - Article
C2 - 32088364
AN - SCOPUS:85082798786
VL - 26
SP - 1071
EP - 1076
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
SN - 1083-8791
IS - 6
ER -