Prophylactic tocilizumab before CD3/4-1bb anti-CD19 car-T cell infusion decreases incidence of severe crs without increased risk of neurotoxicity

Abstract

Background & Aim Anti-CD19 CAR-T cells have demonstrated activity against relapsed/refractory lymphomas. Cytokine release syndrome (CRS) and CAR-T related encephalopathy syndrome (CRES) are well-known complications of CAR-T cell therapy. Tocilizumab, a humanized monoclonal antibody targeting the IL-6 receptor, is approved for treatment of CRS. Our institutional standard was modified to administer prophylactic tocilizumab before infusion CAR-T cell products. We present a retrospective review of the outcomes of subjects treated with and without prophylactic tocilizumab (PT). Methods, Results & Conclusion METHODS:Lymphoma patients (pts) treated with anti-CD19 CAR-T cells were included. Prior to institution of PT, pts received this agent only if they presented evidence of CRS grade 2 or higher. In May 2019, our institutional practice changed to provide tocilizumab 8mg/kg, 1 hour prior to infusion of CAR-T cell product. CRS was measured according to the ASTCT Consensus Grading, whereas CRES was measured using the CARTOX-10 criteria. RESULTS: 18 relapsed / refractory lymphoma pts were treated with antiCD19 CAR-T cells; 10 pts received PT. Median follow up was 217 (range 30 – 534) days.Baseline characteristics are listed in table 1.Both groups were similar. Baseline lymphocyte counts, C – reactive protein (CRP) and ferritin were comparable between groups (Table 2).CRS grade >1 was observed in 5 pts (62.5%) without PT and in 2 pts (20%) treated with PT (p = 0.05). There was no significant difference in the incidence of all grade CRES (no PT: 3/8 pts; PT 2/10 pts, p=0.411).There was a statistically significant difference in the peak CRP and peak ferritin without difference in the peak lymphocyte count.5/8 (63%) pts without PT had complete response vs. 8/10 pts with PT.All pts had detectable Anti-CD19 CAR-T cells on day 30. CONCLUSIONS:Use of PT prior to infusion of antiCD19 CAR-T cells with CD3zeta/4-1BB co-stimulatory domains is associated with reduced incidence of severe CRS.This decreased rate of grade ≥2 CRS is not associated with impaired disease control and did not result in increased rates of CAR-T associated neurologic toxicity.PT does not appear to affect CAR-T cell persistence or time to peak CAR-T expansion.