학술논문
Transient acute kidney injury after chimeric antigen receptor T-cell therapy in patients with hematological malignancies.
Document Type
Academic Journal
Author
León-Román J; Nephrology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Research, CSUR National Unit of Expertise for Complex Glomerular Diseases of Spain, Barcelona, Spain.; Iacoboni G; Department of Hematology, Vall d'Hebron University Hospital, Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron, Barcelona, Spain.; Department of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain.; Bermejo S; N ephrology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Research, CSUR National Unit of Expertise for Complex Glomerular Diseases of Spain, Barcelona, Spain.; Carpio C; Department of Hematology, Vall d'Hebron University Hospital, Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron, Barcelona, Spain.; Bolufer M; N ephrology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Research, CSUR National Unit of Expertise for Complex Glomerular Diseases of Spain, Barcelona, Spain.; García-Carro C; Nephrology Department, San Carlos Clinical University Hospital, Madrid, Spain.; Sánchez-Salinas M; Department of Hematology, Vall d'Hebron University Hospital, Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron, Barcelona, Spain.; Alonso-Martínez C; Pharmacy Department, Vall d´Hebron Hospital Universitari, Vall d´Hebron Barcelona Hospital Campus, Barcelona, Spain.; Bestard O; N ephrology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Research, CSUR National Unit of Expertise for Complex Glomerular Diseases of Spain, Barcelona, Spain.; Barba P; Department of Hematology, Vall d'Hebron University Hospital, Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron, Barcelona, Spain.; Soler MJ; N ephrology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Research, CSUR National Unit of Expertise for Complex Glomerular Diseases of Spain, Barcelona, Spain.
Source
Publisher: Oxford University Press Country of Publication: England NLM ID: 101579321 Publication Model: eCollection Cited Medium: Print ISSN: 2048-8505 (Print) Linking ISSN: 20488505 NLM ISO Abbreviation: Clin Kidney J Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2048-8505
Abstract
Background: Acute kidney injury (AKI) occurs in 30% of patients infused with chimeric antigen receptor (CAR) T-cells. The purpose of this study was to identify risk factors and long-term outcomes after AKI in patients who received CAR T-cell therapy.
Methods: Medical records of 115 adult patients with R/R hematological malignancies treated with CD19-targeted CAR T-cells at Vall d'Hebron University Hospital between July 2018 and May 2021. Baseline demographic data including age, gender, ethnicity, body mass index (BMI), and co-morbidities, as well as the type of hematological neoplasia and prior lines of therapy were collected. Laboratory parameters including serum creatinine and whole blood hemoglobin were retrospectively reviewed and values were gathered for days +1, +7, +14, +21, and +28 post-infusion.
Results: A total of 24/115 (21%) patients developed AKI related to CAR T-cell therapy; 6/24 with AKI over chronic kidney disease (CKD). Two patients had AKI in the context of lymphodepleting (LD) chemotherapy and the other 22 after CAR T-cell infusion, starting at day+1 in 3 patients, day+7 in 13 patients, day +14 in 1 patient, day+21 in 2 patients, and day+28 in 3 patients. Renal function was recovered in 19/24 (79%) patients within the first month after infusion. Male gender, CKD, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS) were associated with AKI. Male gender, CKD, ICANS grade ≥3 and CRS grade ≥2 were identified as independent risk factors for AKI on multivariable analysis. In terms of the most frequent CAR T-cell related complications, CRS was observed in 95 (82%) patients and ICANS in 33 (29%) patients. Steroids were required in 34 (30%) patients and tocilizumab in 37 (32%) patients. Six (5%) patients were admitted to the intensive care unit (1 for septic shock, 4 for CRS grade ≥2 associated to ICANS grade ≥2, and 1 for CRS grade ≥3). A total of 5 (4.4%) patients died in the first 30 days after CAR T-cell infusion for reasons other than disease progression, including 4 cases of infectious complications and 1 of heart failure.
Conclusion: Our results suggest that AKI is a frequent but mild adverse event, with fast recovery in most patients.
Competing Interests: M.J.S. reports personal fees from NovoNordisk, Jansen, Mundipharma, AstraZeneca. Esteve, Fresenius, Ingelheim Lilly, Vifor, ICU, Pfizer, Bayer, Travere Therapeutics, GE Healthcare and grants and personal fees from Boehringer Ingelheim, outside the current study. She is also member of the CKJ Editorial Board. C.G.-C. reports scientific advisory boards participation, grants and personal fees from Astra Zeneca, Esteve, Novonortis, Boehringer Ingelheim, Astellas, Otsuka, Novartis, Mundifarma, Baxter, Alexion, and Vifor. She is also member of the CKJ Editorial Board. G.I. reports consultancy and/or Honoraria from Novartis, Kite/Gilead, Bristol-Myers Squibb, Abbvie, Autolus, Sandoz, Miltenyi, AstraZeneca. P.B. reports consultancy: Allogene, Amgen, BMS, Gilead, Miltenyi biomedicine, Incyte, Novartis, Pfizer. DSMB (Clinical Trial): Miltenyi Biotec. Speaker: Amgen, BMS, Gilead, Novartis, Pfizer. Travel and accommodation: Gilead, Novartis, Pfizer.
(© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)
Methods: Medical records of 115 adult patients with R/R hematological malignancies treated with CD19-targeted CAR T-cells at Vall d'Hebron University Hospital between July 2018 and May 2021. Baseline demographic data including age, gender, ethnicity, body mass index (BMI), and co-morbidities, as well as the type of hematological neoplasia and prior lines of therapy were collected. Laboratory parameters including serum creatinine and whole blood hemoglobin were retrospectively reviewed and values were gathered for days +1, +7, +14, +21, and +28 post-infusion.
Results: A total of 24/115 (21%) patients developed AKI related to CAR T-cell therapy; 6/24 with AKI over chronic kidney disease (CKD). Two patients had AKI in the context of lymphodepleting (LD) chemotherapy and the other 22 after CAR T-cell infusion, starting at day+1 in 3 patients, day+7 in 13 patients, day +14 in 1 patient, day+21 in 2 patients, and day+28 in 3 patients. Renal function was recovered in 19/24 (79%) patients within the first month after infusion. Male gender, CKD, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS) were associated with AKI. Male gender, CKD, ICANS grade ≥3 and CRS grade ≥2 were identified as independent risk factors for AKI on multivariable analysis. In terms of the most frequent CAR T-cell related complications, CRS was observed in 95 (82%) patients and ICANS in 33 (29%) patients. Steroids were required in 34 (30%) patients and tocilizumab in 37 (32%) patients. Six (5%) patients were admitted to the intensive care unit (1 for septic shock, 4 for CRS grade ≥2 associated to ICANS grade ≥2, and 1 for CRS grade ≥3). A total of 5 (4.4%) patients died in the first 30 days after CAR T-cell infusion for reasons other than disease progression, including 4 cases of infectious complications and 1 of heart failure.
Conclusion: Our results suggest that AKI is a frequent but mild adverse event, with fast recovery in most patients.
Competing Interests: M.J.S. reports personal fees from NovoNordisk, Jansen, Mundipharma, AstraZeneca. Esteve, Fresenius, Ingelheim Lilly, Vifor, ICU, Pfizer, Bayer, Travere Therapeutics, GE Healthcare and grants and personal fees from Boehringer Ingelheim, outside the current study. She is also member of the CKJ Editorial Board. C.G.-C. reports scientific advisory boards participation, grants and personal fees from Astra Zeneca, Esteve, Novonortis, Boehringer Ingelheim, Astellas, Otsuka, Novartis, Mundifarma, Baxter, Alexion, and Vifor. She is also member of the CKJ Editorial Board. G.I. reports consultancy and/or Honoraria from Novartis, Kite/Gilead, Bristol-Myers Squibb, Abbvie, Autolus, Sandoz, Miltenyi, AstraZeneca. P.B. reports consultancy: Allogene, Amgen, BMS, Gilead, Miltenyi biomedicine, Incyte, Novartis, Pfizer. DSMB (Clinical Trial): Miltenyi Biotec. Speaker: Amgen, BMS, Gilead, Novartis, Pfizer. Travel and accommodation: Gilead, Novartis, Pfizer.
(© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)