Prognostic impact of dose, duration, and timing of corticosteroid therapy in patients with large B-cell lymphoma treated with standard of care axicabtagene ciloleucel (Axi-cel).

Abstract

8011 Background: Corticosteroids are commonly used for management of severe toxicities associated with chimeric antigen receptor (CAR) T-cell therapy. However, it remains unclear whether the dose, duration, and timing of corticosteroid therapy may impact clinical efficacy of CAR T-cell therapy. Methods: This is a retrospective analysis of patients with relapsed or refractory LBCL treated with standard of care axi-cel at MD Anderson Cancer Center, Houston, Texas between 01/2018 and 05/2019 (data cut-off 12/21/2019). Progression-free survival (PFS) was defined as time from axi-cel infusion to progression/death or last follow-up, and the Breslow test was used for comparisons between subgroups. Results: One hundred patients with relapsed or refractory LBCL were included in the study, and 60 (60%) received corticosteroids for management of toxicities after axi-cel infusion. There was no significant difference in baseline tumor burden, disease stage or international prognostic index between the 2 groups. The median cumulative dexamethasone-equivalent dose was 186 mg (range, 8-1803 mg) and the median duration of corticosteroid treatment was 9 days (range 1-30); 45 (45%) patients started corticosteroid treatment between day 0 and 7, and 15 (15%) beyond day 7. After a median follow-up of 10 months (95% CI 8-10 months), median PFS was 8 months (95% CI, 3-13 months), and use of corticosteroids (any dose) showed a trend for association with shorter PFS (6 vs 9 months, p = 0.13). Use of high-dose corticosteroids (Quartiles (Q) 3-4, 195-1803 mg) significantly associated with shorter PFS (2 vs 9 months, p = 0.005). A trend for shorter PFS was observed among patients receiving corticosteroids for a prolonged time (Q3-Q4, 10-30 days) (5 vs 8 months, p = 0.12) and among patients starting corticosteroids within the first 7 days after axi-cel infusion (6 vs 11 months, p = 0.07). At most recent follow-up, 36 patients died, 28 of progression. Median overall survival has not been reached, and was significantly shorter among patients who received corticosteroids (13 vs not reached, p = 0.006). Conclusions: Early and prolonged use of high-dose corticosteroids is associated with early progression and death in patients with LBCL treated with axi-cel. Additional evaluation is needed to understand the mechanism underlying this association.

Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy

“…Most studies indicate that the use of tocilizumab does not seem to affect the efficacy of CAR T cells 10 , 15 , 86 . However, the data on the effects of corticosteroids on CAR T cell efficacy are conflicting, with some studies indicating no impact but others showing adverse clinical outcomes with increased risk of early progression and death 10 , 87 , 88 . This further highlights the need for better understanding of the pathophysiological mechanisms of CRS and ICANS and the development of novel strategies for their management.…”

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events

“…Additionally, a retrospective analysis of 100 patients with RR large B cell lymphoma treated with axicabtagene ciloleucel found a trend for shorter progression-free survival (PFS) among patients receiving corticosteroids for a prolonged time. 102 …”

“… 118 However, a trend towards shorter PFS has been observed in patients with lymphoma treated with axicabtagene ciloleucel who received longer and earlier intervention with steroids. 102 …”

Clinical Perspective: Treatment of Aggressive B Cell Lymphomas with FDA-Approved CAR-T Cell Therapies

“…Although prolonged steroid use has also been associated with poorer outcomes, it is unclear if this is a result of higher risk disease features and subsequent toxicity or steroid use itself. 61…”