Efficacy of Siltuximab for Chimeric Antigen Receptor T-Cell Therapy Toxicities - a Multicenter Retrospective Analysis

Introduction Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) can affect a significant number of patients (pts) receiving Chimeric Antigen Receptor T-Cell therapies (CAR-T). Pts who develop CRS refractory to tocilizumab or ICANS refractory to steroids have few treatment options. Siltuximab, a mAb binding circulating IL-6, has been proposed to have clinical activity in both CRS and ICANS (Patel, ASH, 2022; Narkhede, TCT, 2023). This study assesses the efficacy of siltuximab for managing CRS and ICANS in a real-world cohort from six academic medical centers. Methods We conducted a multicenter retrospective review of adult pts with hematologic malignancies treated with CAR-T therapy who received siltuximab for treatment of CRS and/or ICANS between January 2020 and August 2022. Pts who died within 48 hours of siltuximab administration (n=2) were excluded. The co-primary endpoints were to identify the percentage of pts who had improvement in CRS or ICANS after receiving siltuximab. Secondary endpoints included time to improvement of CRS or ICANS and overall survival (OS) from the date of CAR-T infusion. Time to event endpoints were evaluated by Kaplan-Meier methodology. Results Fifty-two pts were eligible and evaluated. Table 1 describes patient and disease characteristics along with cell therapy product details. Fifty-one pts (98%) developed CRS and 34 pts (65%) developed ICANS. Tocilizumab was administered in 52% of pts and corticosteroids were administered in 69% of pts.The reason for siltuximab administration in the majority of patients was tocilizumab shortage (50%) or steroid refractory ICANS (33%). At the time of siltuximab administration, 42 pts (81%) had evidence of CRS, 28 pts (54%) had evidence of ICANS and 18 pts (35%) had concurrent CRS and ICANS.Thirty-six pts (86%) had improved CRS grade following siltuximab with median time to CRS resolution being 1.5 days (range 0-18). Four pts (50%) with tocilizumab refractory CRS had improved CRS grade after siltuximab. Nineteen pts (68%) had improved ICANS grade following siltuximab with median time to ICANS resolution being 5 days (range 1-40). Thirteen pts (76%) with steroid refractory ICANS had improved ICANS grade after siltuximab.Twenty-one pts had died at the time of data collection; 4 deaths were deemed secondary to CAR-T toxicity. The median OS was 13.8 months (95% CI 9.6-NR) and was not statistically different based on indication of CAR-T therapy, Figure 1. Conclusions To our knowledge, this is the largest cohort of pts treated with siltuximab for CRS and/or ICANS following CAR-T therapy. Siltuximab appeared to be effective for both CRS and ICANS, including refractory toxicities. These data support the use of siltuximab for refractory CRS and ICANS and warrant further investigation of siltuximab in earlier line of therapy for CRS and ICANS management.