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 affect 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) 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% confidence interval, 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.

Keywords: CART; NEOPLASIA/lymphomas and other lymphoproliferative conditions; corticosteroid; lymphoma; outcome.

Graphical abstract

Figure 1.

Prognostic impact of corticosteroid use on PFS and OS. Association between use of (A,E) corticosteroids, (B,F) cumulative corticosteroid dose, (C,G) duration, and (D,H) timing and (A-D) PFS and (E-H) OS in patients with relapsed or refractory large B-cell lymphoma treated with axi-cel. No significant difference in complete response rate was observed based on corticosteroid use, dose, duration, and timing. The association between use of higher cumulative dose of corticosteroids and shorter PFS was maintained when limiting the analysis to the 43 patients with high-grade ICANS (P = .05). The association between higher cumulative dose (P = .04) and shorter OS was maintained when limiting the analysis to the 43 patients with high-grade ICANS. Only 2 patients died of infectious complications. Quartiles for cumulative dexamethasone-equivalent dose: first quartile (Q1), 8-116 mg; second quartile (Q2), 118-186 mg; third quartile (Q3), 195-390 mg; and fourth quartile (Q4), 440-1083 mg. Quartiles for duration of corticosteroid use: Q1, 1-6 days; Q2, 7-9 days; Q3, 10-14 days; and Q4, 15-30 days. CS, corticosteroid; m, median. Analyzing the data by treating LDH as a continuous variable did not show any significant differences in the LDH levels based on corticosteroid use (P = .21), dose (P = .22), duration (P = .09), or timing (P = .07).