Common laboratory measures of inflammation are associated with immune-related toxicities after chimeric antigen receptor (CAR) T-cell therapy and may guide risk-stratification, according to research published in Blood Advances.

CAR-T therapy is associated with a risk of developing cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). It is difficult to predict which patients are at higher risk for immune-related toxicities.

The endothelial activation and stress index (EASIX) score is used as a surrogate marker of endothelial activation and is used to predict transplant-related toxicities. EASIX score is determined by (creatinine X lactate dehydrogenase)/platelets.

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The study authors evaluated whether EASIX score before lymphodepletion is related to CRS and ICANS. They also evaluated other inflammatory biomarkers to determine if they have prognostic significance.

The study collected prospective data on 171 adults with relapsed or refractory large B-cell lymphoma (LBCL). Patients received lymphodepleting chemotherapy followed by the CAR T cells axicabtagene ciloleucel (axi-cel).

Within the first 30 days after CAR-T infusion, 94% of patients had CRS of any grade and 64% of patients had ICANS of any grade.

EASIX score was the most strongly associated factor with grades 2 to 4 CRS. High ferritin levels were also associated with high EASIX score and with grades 2 to 4 CRS. High EASIX scores were also associated with grade 2 to 4 ICANS.

The authors concluded that EASIX score before lymphodepletion and measures of ferritin and C-reactive protein (CRP) are associated with the incidence and severity of CRS and ICANS in patients with LBCL who are treated with axi-cel. They recommend a modified version of the scores with EASIX-F for CRS and EASIX-FC for ICANS risk stratification. The authors noted that the modified EASIX score had a stronger association with immune-related toxicities than each measure on its own.

The study had several limitations, including a small sample size, no validation cohort, and the use of only one type of CAR-T product. Larger studies are needed to validate prognostic measures for CAR-T therapy, but these results may aid in choosing high-risk patients for clinical trials.

Disclosure: The study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Greenbaum U, Strati P, Saliba RM, et al. CRP and ferritin in addition to the EASIX score predict CAR-T-related toxicity. Blood Adv. 2021;5(14):2799-2806. doi:10.1182/bloodadvances.2021004575