Effect of prophylactic corticosteroids on toxicities and outcomes in CAR T-cell therapy: A cohort study.

Abstract

7030 Background: Common toxicities associated with infusion of Chimeric antigen receptor T-Cell (CAR T-cell) therapy include cytokine release syndrome (CRS) and immune-effector-cell-associated neurotoxicity syndrome (ICANS). While early steroid use has correlated with a reduced risk of high-grade CRS and ICANS, there is conflicting data regarding its impact on CAR-T efficacy. We aim to study the impact of prophylactic steroid use on toxicities and outcomes at our institution. Methods: We performed a single-center comparative analysis between two patient cohorts at higher risk of CRS and ICANS based on elevated inflammatory markers, (ferritin ≥400 ng/mL and CRP ≥4 mg/dL). One cohort received prophylactic dexamethasone 10 mg on days 0,1, and 2. Univariate statistics were calculated using X2, Fisher’s exact tests, and ANOVAs, where appropriate. Kaplan Meier was used to estimate overall survival (OS) and progression-free survival (PFS) and compared using the log-rank test. Results: Out of 63 patients with high ferritin and CRP, 10 patients received prophylactic steroids (Group PS) and 53 patients did not (Group NPS). In the NPS group, 46 patients had a primary diagnosis of non-Hodgkin lymphoma and 7 had a diagnosis of multiple myeloma. In the PS group, 9 had non-Hodgkin lymphoma and 1 had multiple myeloma. The median age at CAR-T was 58 years in PS and 64 years in NPS group (p=0.48). The rate of CRS grade ≥3 was higher in the NPS group compared to the PS group, (47.2 vs 20%, p=0.26) whereas ICANS grade ≥3 was similar (32% in NPS and 30% in PS group). More patients achieved a complete response in the PS group (60%) compared to the NPS group (30.2%). The1-year PFS was higher in PS group compared to NPS (60% vs 28%,p=0.08) which was also reflected in the 1-year OS (70% vs 38%, p=0.10). At a median follow-up of 22 months, 70% patients were alive in the PS group compared to 28.3% patients in the NPS group. Conclusions: Our study shows lower rates of CRS and a pattern towards higher rates of complete remission and survival benefit in patients undergoing CAR T-cell therapy receiving prophylactic steroids. The data must be interpreted with caution given the small sample size, but it warrants the need for future studies. Outcomes of patients by prophylactic steroid status (n=63). Parameter NPS (n=53) % PS (n=10) % p-value* Best Response 0.42 Complete Response 16 30.2 6 60.0 Partial Response 4 7.5 1 10.0 Stable Disease 2 3.8 0 0.0 Progressive Disease 24 45.3 3 30.0 NE* 7 13.2 0 0.0 Disease progression 0.30 No 25 47.2 7 70.0 Yes 28 52.8 3 30.0 Time to disease progression, days, median (range) 66.5 5-996 96 92-158 0.75 Median follow-up among survivors (n=22), months (range) 46.5 9-73.8 11.4 8.3-24.2 <0.01 Alive 15 28.3 7 70.0 Dead 38 71.7 3 30.0 2nd Cancer 1 2.6 1 33.3 CNS failure 2 5.3 0 0.0 COVID 1 2.6 0 0.0 Disease 23 60.5 2 66.7 Hemorrhage 1 2.6 0 0.0 Infections 9 23.7 0 0.0 Unknown 1 2.6 0 0.0 NE*= not included in analysis.