Acute kidney injury after chimeric antigen receptor T-cell therapy is associated with inferior survival in patients with relapsed/refractory large B-cell lymphoma.

in British journal of haematology by John Sharp, Qiuhong Zhao, Timothy J Voorhees, David A Bond, Yazeed Sawalha, John Reneau, Audrey Sigmund, Walter Hanel, Lalit Sehgal, Lapo Alinari, Robert Baiocchi, Jonathan E Brammer, Kami Maddocks, Beth Christian, Evandro Bezerra, Nathan Denlinger, Sumithira Vasu, Marcos De Lima, Jason Prosek, Narendranath Epperla

TLDR

  • The study found that 18% of patients undergoing CAR-T therapy for relapsed/refractory large B-cell lymphoma developed acute kidney injury (AKI), with a higher risk associated with chronic kidney disease and receipt of axicabtagene ciloleucel.

Abstract

Baseline risk factors for acute kidney injury (AKI) during chimeric antigen receptor T-cell (CAR-T) therapy are not well described. Hence, we evaluated the incidence and risk factors associated with AKI among patients undergoing CAR-T for relapsed/refractory large B-cell lymphoma. Among 155 patients, 28 (18%) developed AKI with a median time-to-peak creatinine from CAR-T of 9.5 days (range = 3-30). Aetiologies included volume depletion (n = 20, 71%), cytokine release syndrome (n = 5, 18%), nephrotoxins (n = 5, 18%), tumour lysis syndrome (n = 1, 4%) and multifactorial (n = 6, 21%). On univariable analysis, a history of chronic kidney disease (CKD) relative risk (RR 3.5, 95% CI: 1.9-6.6, p < 0.01), receipt of axicabtagene ciloleucel (RR 2.1, 95% CI: 1.1-4.2, p = 0.04), elevated ferritin (RR 3.1, 95% CI: 1.1-8.4, p = 0.03) and serum creatinine level (RR 2.9, 95% CI: 1.4-6.2, p < 0.01) were associated with AKI. On multivariable analysis, a history of CKD adjusted relative risk (aRR 3.5, 95% CI: 1.9-6.4, p < 0.01) and receipt of axicabtagene ciloleucel (aRR 2.1, 95% CI: 1.1-4.0, p = 0.03) retained statistical significance. Four (2.6%) patients required renal replacement therapy during CAR-T. Twenty-five of 28 patients with AKI had renal recovery with a median time to recovery of 14 days (range = 5-85). Of those without renal recovery, two required long-term haemodialysis and one experienced disease progression and died 34 days after CAR-T. Patients with AKI had shorter median PFS (2.4 vs. 6.9 months, p = 0.02) and OS (7.8 vs. 29.7 months, p < 0.01). Additional research is needed to obviate the risk of renal toxicity and improve post-CAR-T outcomes.

Overview

  • The study aimed to identify the incidence and risk factors associated with acute kidney injury (AKI) among patients undergoing chimeric antigen receptor T-cell (CAR-T) therapy for relapsed/refractory large B-cell lymphoma.
  • The study included 155 patients and found that 28 (18%) developed AKI, with a median time-to-peak creatinine from CAR-T of 9.5 days.
  • The study's primary objectives were to identify the baseline risk factors for AKI and to investigate the incidence and outcomes of AKI in patients undergoing CAR-T therapy.

Comparative Analysis & Findings

  • The study found that the incidence of AKI was 18%, with a median time-to-peak creatinine from CAR-T of 9.5 days.
  • On univariable and multivariable analysis, a history of chronic kidney disease (CKD) and receipt of axicabtagene ciloleucel were associated with a higher risk of AKI.
  • Patients with AKI had a shorter median progression-free survival (PFS) and overall survival (OS) compared to patients without AKI.

Implications and Future Directions

  • The study highlights the importance of identifying patients at risk of AKI before CAR-T therapy and implementing strategies to prevent or reduce the risk of AKI.
  • Future research should focus on developing effective treatments for AKI in patients undergoing CAR-T therapy and improving post-CAR-T outcomes.
  • The study's findings suggest that incorporating kidney function assessments and monitoring into CAR-T protocols may be necessary to prevent and manage AKI.
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