Pre-Apheresis Cortisol Levels: Does It Correlate to Incidence of CRS?

Introduction Chimeric antigen receptor (CAR)–T cell therapy is associated with cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). These immune-related toxicities can be severe or life-threatening. It is difficult to predict which patients will have these reactions. Some studies have tried to assess whether inflammatory biomarkers such as ferritin and interleukin-6 correlate to toxicity. Our study aims to assess whether cortisol as an independent biomarker has some predictive effect on incidence of CRS and ICANS. Methods We conducted a single-center retrospective analysis using patients with relapsed and refractory aggressive B-cell lymphoma who were treated with CART cell therapy between August 2018 and December 2022. Demographic, clinical, laboratory, and pathologic data were obtained from clinical records. CRS and ICANS were assessed daily using the CTCAE v 5. Fisher's exact tests were used for the test of associations among categorical variables. Pearson's Chi-square tests were used for analyzing incidence rate ratios of CRS and ICANS. Kaplan-Meier and log-rank tests were used to compare overall survival (OS) and progression-free survival (PFS) between different treatment exposures. PFS and OS were calculated from time of infusion. Results We identified 46 patients with relapsed/refractory large B cell lymphoma for analysis, of which 29 (63%) were male and 17 (34%) were female. The average age of patients was 63 (SD ±11) and most (82%) patients had ECOG 0-1. CART agents used were Tisagenleucel (31%), Axicabtagene ciloleucel (52%), and Lisocabtagene maraleucel (17%). The average follow up was 17 months. Most patients developed either a grade 1 or grade 2 CRS (33% and 37%, respectively), and only 3% of patients developed grade 3 or above. As for neurotoxicity, most patients (59%) did not develop ICANS, however of those who did, 19% were grade 3 and beyond. The average AM cortisol level prior to CART infusion was 12 ug/dL (AM cortisol reference range: 6-25 ug/dL). Patients with a baseline cortisol <12 ug/dL had a similar overall survival to those with a baseline cortisol >12 ug/dL (HR 0.82, p=0.7) with no difference in incidence of CRS (HR 0.63, p=0.27) and ICANS (HR 1.77, p=0.46). Patients with a CRP> 8 mg/L at baseline had a higher incidence of CRS (HR=2.46, p=0.04) than patients with CRP <8 mg/L. There was also a trend towards a worse overall survival in those with CRP >8 as compared to those <8 (HR 3.22, p=0.06). Lastly, there was no significant correlation observed between CRP and cortisol. Conclusion Inflammatory markers are monitored in patients who receive CART. Previous data suggest that higher baseline CRP and Ferritin levels predict for CRS and ICANS. Our data suggest that baseline cortisol level does not appear to have a similar effect. Additional studies analyzing trends in these inflammatory markers may provide more insight.