Relationship of CRP and Ferritin Levels and Length of ICU Stay in Patients with B-Cell Lymphomas Treated with Axicabtagene Ciloleucel (axi-cel)

Abstract

Background Axicabtagene ciloleucel (Axi-cel) is an autologous chimeric antigen receptor (CAR) T-cell therapy which is effective in relapsed/refractory (R/R) anti-CD19 B-cell leukemia and lymphomas. Axi-cel is associated with unique toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Management of these toxicities often requires ICU admission. Scoring systems have been developed to grade severity of these toxicities and help guide treatment escalation as needed; however, they provide little insight into duration of ICU stay. C-reactive protein (CRP) and ferritin are serum inflammatory markers associated with onset and persistence of CAR-T cell related toxicity. Here, we examine the relationship between these serum inflammatory markers and the duration of ICU stay in CAR-T Cell therapy recipients. Methods We conducted a retrospective analysis of patients (pts) treated with axi-cel across two Mayo Clinic campuses (Jacksonville and Phoenix) from 06/01/2018 until 07/01/2019. Primary objective was to examine the relationship between serum ferritin and CRP levels with need for and length of ICU stay in axi-cel treated pts. Results Our study population consisted of 18 pts (11 males, 61%), median age of 51 (26-67) years. Nine were admitted to the ICU during their initial hospitalization. The median time from axi-cel infusion to ICU admission was 4 (2-8) days with a median ICU length of stay of 4 (2-24) days. All 9 admitted pts developed CRS: grade 1 (1), grade 2 (7), and grade 3 (1); 7 pts developed ICANS: grade 2 (1), grade 3 (1) and grade 4 (5). Eight of the 9 non-ICU pts developed CRS: grade 1 (5) and grade 2 (3). Three pts developed grade 1 ICANS. Grade of CRS and ICANS were higher in ICU pts vs non-ICU pts (p=0.01 and p=0.001, respectively). There was no correlation between the severity of CRS and length of ICU stay (correlation of 0.07, p=0.86) or severity of ICANS and length of ICU stay (correlation of 0.36, p=0.35). Initial median CRP level at infusion was higher in ICU vs. non-ICU pts (25.2 mg/L vs. 13.9 mg/L); however, this difference was not significant, p=0.38. Initial ferritin levels at infusion were over 2-fold higher, albeit not statistically significant, in ICU pts (837 mcg/L vs 387 mcg/L, p=0.21). The median CRP at the time of ICU admission was 54.1 mg/L (3.2-341) mg/L. There was no significant correlation between CRP levels at time of ICU admission and length of ICU stay (correlation of 0.067, p = 0.86). The median ferritin level at the time of ICU admission was 2010mcg/L (344-10943). There was a strong direct correlation between serum ferritin levels and length of ICU stay (correlation of 0.93, p = 0.0003). Conclusions This study showed that an elevated ferritin level at the time of escalation of medical care may be indicative of anticipated prolonged ICU hospitalization in axi-cel recipients.