Siltuximab demonstrated promising safety and efficacy for the treatment of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) associated with chimeric antigen receptor (CAR) T-cell therapy, according to the results of an interim analysis of a phase 2 trial presented at the 2023 Tandem Transplantation and Cellular Therapy Meetings of ASTCT and CIBMTR.
Siltuximab is an anti-IL-6-binding monoclonal antibody. Tocilizumab, another anti-IL-6 antibody, is currently used to treat CRS and ICANS, but causes paradoxical increases in circulating IL-6 levels. The aim of this study was to determine if siltuximab is also effective for the treatment of CRS and ICANS.
For this interim analysis, 6 patients treated with CAR T-cell therapy for hematologic malignancy who developed persistent grade 1 or grade 2 CRS or ICANS were treated with a single dose of siltuximab. A second dose could be administered if the severity of CRS or ICANS persisted. The primary endpoint was resolution within 14 days of siltuximab treatment and secondary endpoints included resolution of ICANS within 28 days.
The median age of the patients was 63. There were 3 patients with diffuse large B-cell lymphoma, 2 with multiple myeloma, and 1 with follicular lymphoma. All patients had grade 1 or 2 CRS or ICANS at enrollment.
CRS developed among all patients, and ICANS among 4. The complete response (CR) rate for CRS was 83% with a median time to CRS resolution was 1 hour from the first dose of siltuximab. There were 2 patients who required a second dose at 12 hours.
There were 75% of patients with ICANS who achieved CR. For 3 of the patients, the median time to resolution was 45 hours. Corticosteroids were required for all 4 patients. One patient did not respond to siltuximab and developed grade 3 disease that required intensive care.
There were no infusion-related reactions. The authors concluded that “siltuximab appears to have demonstrated safety and efficacy for managing CRS and ICANS in patients receiving CAR T-cell therapy.” Based on these results, additional patients will be accrued to the study.
Disclosures: This study was supported in part by EUSA Pharma Inc. Please see the original reference for a full list of disclosures.
Narkhede M, Di Stasi A, Bal S, et al. Interim analysis of investigator-initiated phase 2 trial of siltuximab in treatment of cytokine release syndrome and immune effector cell associated neurotoxicity related to CAR T-cell therapy. Presented at: 2023 Tandem Meetings Transplantation and Cellular Therapy Meetings of ASTCT and CIBMTR; February 15-19, 2023. Abstract 165.