Prognostic impact of corticosteroids on efficacy of chimeric antigen receptor T-cell therapy in large B-cell lymphoma

Abstract

Corticosteroids are commonly used for the management of severe toxicities associated with chimeric antigen receptor (CAR) T-cell therapy. However, it remains unclear whether their dose, duration, and timing may impact clinical efficacy. Here, we determined the impact of corticosteroids on clinical outcomes in patients with relapsed or refractory large B-cell lymphoma treated with standard of care anti-CD19 CAR T-cell therapy. Among 100 patients evaluated, 60 (60%) received corticosteroids for management of CAR T-cell therapy-associated toxicities. 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). Corticosteroid treatment was started between days 0 and 7 in 45 (75%) patients and beyond day 7 in 15 (25%). After a median follow-up of 10 months (95% CI 8-12 months), use of higher cumulative dose of corticosteroids was associated with significantly shorter progression-free survival. More importantly, higher cumulative dose of corticosteroids, and prolonged and early use after CAR T-cell infusion were associated with significantly shorter overall survival. These results suggest that corticosteroids should be used at the lowest dose and for the shortest duration and their initiation should be delayed whenever clinically feasible, while managing CAR T-cell therapy-associated toxicities.

The Association Between Glucocorticoid Administration and the Risk of Impaired Efficacy of Axicabtagene Ciloleucel Treatment: A Systematic Review

“…Our study found that if only according to the glucocorticoids use for investigating its impact on the efficacy of CAR-T cell therapy generally drew negative conclusions. When the cumulative dose, duration and timing of glucocorticoids were further analyzed, a study found that high-dose glucocorticoids were associated with shorter PFS, and the high dose, prolonged duration, and timing all significantly impacted OS of patients (25). But another study of which major drawback was the undefined cut-off value indicated that the dose and duration of glucocorticoids had no effect on PFS and OS (26).…”

“…There was only one eligible controlled study that specifically investigated patients receiving glucocorticoids as an intervention after Axi-cel therapy, which may be due to the limited clinical experience and treatment options available for ICANS management and the need for emergency treatment following adverse reactions in patients (25). Therefore, all the studies we included were retrospective studies or case reports.…”

“…A total of four studies investigated the effects of glucocorticoids use on PFS (24)(25)(26)(27). Both Sesques et al and Nastoupil et al found no association between glucocorticoids use and PFS (24,27).…”

“…Holtzman et al also assessed the effects of duration (P = 0.32), total dose (P = 0.59), average daily dose and initial high-dose pulsing of glucocorticoids on PFS, however, no specific cut-off value was provided (26). Strati et al found no association between PFS and glucocorticoids use (P = 0.13), but when the cumulative dose and duration of the glucocorticoids were considered (cut-off values: 186 mg, 9 days, respectively), higher dose led to shorter PFS (p = 0.005), prolonged duration did not affect PFS (p = 0.12), and patients who early used glucocorticoids within 7 days tended to have worse PFS (p = 0.07) (25).…”

“…As with PFS, the same four studies evaluated the impact of glucocorticoids on OS (24)(25)(26)(27). (25,26). In the phase-1 ZUMA-1 trial, three patients achieved complete response at 12 months, of whom one patient received glucocorticoids for the management of both CRS and ICANS (28).…”