Population-Based External Validation of the EASIX Scores to Predict CAR T-Cell-Related Toxicities

Janneke W. de Boer, Kylie Keijzer, Elise R.A. Pennings, Jaap A. van Doesum, Anne M. Spanjaart, Margot Jak, Pim G.N.J. Mutsaers, Suzanne van Dorp, Joost S.P. Vermaat, Marjolein W.M. van der Poel, Lisanne V. van Dijk, Marie José Kersten, Anne G.H. Niezink, Tom van Meerten*, on behalf of the Dutch CAR-T Tumorboard Consortium

*Corresponding author for this work

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Abstract

Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) can hamper the clinical benefit of CAR T-cell therapy in patients with relapsed/refractory large B-cell lymphoma (r/r LBCL). To assess the risk of CRS and ICANS, the endothelial activation and stress index (EASIX), the modified EASIX (m-EASIX), simplified EASIX (s-EASIX), and EASIX with CRP/ferritin (EASIX-F(C)) were proposed. This study validates these scores in a consecutive population-based cohort. Patients with r/r LBCL treated with axicabtagene ciloleucel were included (n = 154). EASIX scores were calculated at baseline, before lymphodepletion (pre-LD) and at CAR T-cell infusion. The EASIX and the s-EASIX at pre-LD were significantly associated with ICANS grade ≥ 2 (both p = 0.04), and the EASIX approached statistical significance at infusion (p = 0.05). However, the predictive performance was moderate, with area under the curves of 0.61–0.62. Validation of the EASIX-FC revealed that patients in the intermediate risk group had an increased risk of ICANS grade ≥ 2 compared to low-risk patients. No significant associations between EASIX scores and CRS/ICANS grade ≥ 3 were found. The (m-/s-) EASIX can be used to assess the risk of ICANS grade ≥ 2 in patients treated with CAR T-cell therapy. However, due to the moderate performance of the scores, further optimization needs to be performed before broad implementation as a clinical tool, directing early intervention and guiding outpatient CAR T-cell treatment.

Original languageEnglish
Article number5443
JournalCancers
Volume15
Issue number22
DOIs
Publication statusPublished - 16 Nov 2023

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