Comparison of short- and long-term adverse kidney outcomes after chimeric antigen receptor T cell therapy and autologous hematopoietic stem cell transplant for diffuse large B cell lymphoma

Hanna, Paul E; Strohbehn, Ian A.; Moreno, Daiana; Harden, Destiny; Seethapathy, Harish; Gupta, Shruti; Lee, Meghan; Ouyang, Tianqi; Frigault, Matthew J.; Sise, Meghan E.

doi:10.1038/s41409-022-01767-7

Cited by 2 publications

(3 citation statements)

References 12 publications

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“…The authors confirmed that AKI was usually a mild disease with fast recovery [ 35 ]. The largest study to date, led by Hanna et al , compared the risk of AKI in 232 patients who received CAR T-cell therapy with 414 patients who underwent auto-HCT, confirming no significant differences between both groups in the first 30 days after infusion [ 38 ]. These results are similar to our own findings, indicating that AKI associated with CAR T-cell infusion is a mild complication with a fast recovery.…”

Section: Discussionmentioning

confidence: 99%

“…AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria: grade 1, increase in serum creatinine (SCr) 1.5 to <2-fold of baseline; grade 2, increase in SCr 2- to <3-fold of baseline; grade 3, increase in SCr ≥3-fold of baseline, OR requiring renal replacement therapy, OR SCr ≥4.0 mg/dL [ 37 ]. Chronic kidney disease (CKD) was defined according KDIGO as kidney damage or glomerular filtration rate (GFR) <60 ml/min/1.73 m 2 with CKD-EPI formula for 3 months or more, irrespective of cause [ 38 ]. Recovery of renal function was established following the consensus report of the Acute Disease Quality Initiative (ADQI) [ 39 ].…”

Section: Methodsmentioning

confidence: 99%

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

León-Román,

Iacoboni,

Bermejo

et al. 2024

Clinical Kidney Journal

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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. 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. Our results suggest that AKI is a frequent but mild adverse event, with fast recovery in most patients.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

León-Román,

Iacoboni,

Bermejo

et al. 2024

Clinical Kidney Journal

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“…AKI has been reported in 5-30% of patients post-CAR-T therapy [108][109][110]. The risk of developing AKI, the incidence of chronic kidney function decline in patients (12.5% vs. 12.2%), and the average decline in eGFR from baseline (14.6% vs. 15%, p = 0.28) were not significantly different between CAR-T recipients and HSCT recipients [111]. Additionally, the strongest risk factor for developing chronic kidney function decline was the development of AKI within the first 30days post-CAR-T infusion and there is a trend towards higher rates of AKI and chronic kidney function decline amongst patients with severe CRS [111].…”

Section: Early and Late Organ Supportmentioning

confidence: 91%

Management and Prevention of Cellular-Therapy-Related Toxicity: Early and Late Complications

Mucha

Rajendram

2023

Current Oncology

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Chimeric Antigen Receptor T (CAR-T) cell therapy has dramatically changed prognosis and treatment of relapsed and refractory hematologic malignancies. Currently the 6 FDA approved products target various surface antigens. While CAR-T therapy achieves good response, life-threatening toxicities have been reported. Mechanistically, can be divided into two categories: (1) toxicities related to T-cell activation and release of high levels of cytokines: or (2) toxicities resulting from interaction between CAR and CAR targeted antigen expressed on non-malignant cells (i.e., on-target, off-tumor effects). Variations in conditioning therapies, co-stimulatory domains, CAR T-cell dose and anti-cytokine administration, pose a challenge in distinguishing cytokine mediated related toxicities from on-target, off-tumor toxicities. Timing, frequency, severity, as well as optimal management of CAR T-cell-related toxicities vary significantly between products and are likely to change as newer therapies become available. Currently the FDA approved CARs are targeted towards the B-cell malignancies however the future holds promise of expanding the target to solid tumor malignancies. Further highlighting the importance of early recognition and intervention for early and late onset CAR-T related toxicity. This contemporary review aims to describe presentation, grading and management of commonly encountered toxicities, short- and long-term complications, discuss preventive strategies and resource utilization.

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Comparison of short- and long-term adverse kidney outcomes after chimeric antigen receptor T cell therapy and autologous hematopoietic stem cell transplant for diffuse large B cell lymphoma

Cited by 2 publications

References 12 publications

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

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

Management and Prevention of Cellular-Therapy-Related Toxicity: Early and Late Complications

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