Prophylactic corticosteroid use in patients receiving axicabtagene ciloleucel for large B-cell lymphoma

Abstract

ZUMA-1 (NCT02348216) examined the safety and efficacy of axicabtagene ciloleucel (axi-cel), an autologous CD19-directed chimaeric antigen receptor (CAR)-T cell therapy, in refractory large B-cell lymphoma. To reduce treatment-related toxicity, several exploratory safety management cohorts were added to ZUMA-1. Specifically, cohort 6 investigated management of cytokine release syndrome (CRS) and neurologic events (NEs) with prophylactic corticosteroids and earlier corticosteroid and tocilizumab intervention. CRS and NE incidence and severity were primary end-points. Following leukapheresis, patients could receive optional bridging therapy per investigator discretion. All patients received conditioning chemotherapy (days -5 through -3), 2 × 10⁶ CAR-T cells/kg (day 0) and once-daily oral dexamethasone [10 mg, day 0 (before axi-cel) through day 2]. Forty patients received axi-cel. CRS occurred in 80% of patients (all grade ≤2). Any grade and grade 3 or higher NEs occurred in 58% and 13% of patients respectively. Sixty-eight per cent of patients did not experience CRS or NEs within 72 h of axi-cel. With a median follow-up of 8·9 months, objective and complete response rates were 95% and 80% respectively. Overall, prophylactic corticosteroids and earlier corticosteroid and/or tocilizumab intervention resulted in no grade 3 or higher CRS, a low rate of grade 3 or higher NEs and high response rates in this study population.

Keywords: axi-cel; chimaeric antigen receptor-T cell; corticosteroids; cytokine release syndrome; large B-cell lymphoma; prophylaxis.

Fig 1

Toxicity management in ZUMA‐1. *Only in case of comorbidities or older age. †Only if no improvement with tocilizumab, use standard dose. ‡If no improvement after 24 h. §If no improvement after three days. ||Only for grade 2 or higher NEs with concurrent CRS. AE, adverse event; CRS, cytokine release syndrome; HD, high dose; Mgmt, management; NE, neurologic event. [Colour figure can be viewed at wileyonlinelibrary.com]

Fig 2

(A) Objective response rates (ORRs) and (B) duration of response (DOR) in patients achieving an objective response in ZUMA‐1 cohort 6. For patients who underwent stem cell transplantation before documented progression, DOR was censored at the date of stem cell transplantation. CR, complete response; NE, not estimable; NR, not reported; PR, partial response; SD, stable disease. [Colour figure can be viewed at wileyonlinelibrary.com]

Fig 3

Levels of (A) blood chimaeric antigen receptor (CAR)‐T cells and (B) key soluble serum biomarkers over time. Dashed lines (A) and bars (B) represent the interquartile range. BL, baseline; CRP, C‐reactive protein; GM‐CSF, granulocyte‐macrophage colony‐stimulating factor; IFN, interferon; IL, interleukin; MCP‐1, monocyte chemoattractant protein 1.