Prediction of toxicity in R/R DLBCL treated with Axicabtagene Clioleucel (19-28z CAR T)

Abstract

[Background]: A cytokine release syndrome (CRS) or neurotoxicity described as a chimeric antigen receptor (CAR) T Related Encephalopathy Syndrome (CRES) is one of the main complications while CD19 CAR T has been successful in relapsed/refractory (R/R) B cell malignancies. CRS and/or CRES have been associated with standard biomarkers such as CRP and ferritin but also with cytokines. We report the results of cytokine analysis using a point of care (POC) device to predict immune-related toxicities in patients with R/R DLBCL treated with axicabtagene ciloleucel (axi-cel). [Methods]: Patients treated with commercial axi-cel in Moffitt Cancer Center were included in this study. Serum samples were collected prior to lymphodepleting chemotherapy at baseline and then during hospitalization. Based on 38 serum cytokineś analysis in B-cell acute lymphoblastic leukemia patients treated with 19-28z CAR T and results of published studies, 8 serum proteins were selected to monitor. CRS and CRES were prospectively graded by Lee criteria and CARTOX respectively. [Results]: 41 patients were identified. Median age was 64 years old (76% male). Nonsevere (grade 0-2) and severe (grade 3-5) CRS were observed in 93% and 7% respectively while non-severe and severe CRES were observed in 71% and 29% respectively. 2 patients died in the setting of severe toxicity. Baseline CRP, ferritin, IL-6 levels were significantly elevated in the patients who developed severe CRS and/or CRES. Baseline angiopoietin-2/angipoietin-1 ratio (ANG-2/1) was also correlated with severe CRES. In select cases, monitoring of cytokines provided clinical insight that wasńt evident from standard biomarkers. [Conclusions]: We observed correlations between severe toxicities and elevated serum cytokine levels of baseline IL-6 and ANG-2/1 suggesting that these biomarkers may be utilized to predict severe toxicity in patients treated with CAR T. Monitoring of cytokines using a POC device is feasible and would be useful clinically.