Mayur Narkhede, MD, assistant professor, medicine – hematology & oncology, Department of Medicine, the University of Alabama, Birmingham, discusses findings from a pre-planned interim analysis of a phase 2 trial (NCT04975555) investigating siltuximab (Sylvant), an interleukin-6 binding monoclonal antibody, for the treatment of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) related to CAR T-cell therapy in adult patients with relapsed/refractory large B-cell lymphoma (LBCL), follicular lymphoma (FL), or multiple myeloma who received axicabtagene ciloleucel (Yescarta), idecabtagene vicleucel (Abecma), lisocabtagene ciloleucel (Breyanzi), or tisagenlecleucel (Kymriah).

This study was designed to assess a target of 20 patients in 2 parts, Narkhede says. The first part, a futility assessment, analyzed the first 6 patients enrolled to the study. If 3 or fewer patients did not have complete CRS resolution with siltuximab and required rescue tocilizumab (Actemra), the trial would be futile, Narkhede explains.

Results presented at the 2023 Transplantation and Cellular Therapy Meetings showed interim findings from 6 patients, 3 with LBCL, 1 with FL, and 2 with multiple myeloma, Narkhede says. To be eligible, patients needed to have grade 1 CRS or ICANS for at least 12 hours after CAR T-cell infusion or grade 2 or higher CRS or ICANS. All 6 patients developed CRS and 4 patients developed ICANS.

The primary end point of this study was CRS resolution date within 14 days of first siltuximab infusion. The secondary end point was ICANS resolution rate within 28 days of first siltuximab infusion. Patients received siltuximab at 11 mg/kg.

Of the 6 patients enrolled, 5 had complete CRS resolution with siltuximab, with a median time to resolution of 1 hour from first siltuximab infusion completion, Narkhede emphasizes. Of those 5 patients, 2 needed 2 doses of siltuximab to achieve CRS resolution, Narkhede explains. Of the patients with ICANS, 3 had ICANS resolution with siltuximab, with a median time to resolution of 45 hours.

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Mayur Narkhede, MD, discusses findings from a pre-planned interim analysis of a phase 2 trial investigating siltuximab for the treatment of cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome related to CAR T-cell therapy in adult patients with hematologic malignancies. 

Mayur Narkhede, MD

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Dr. Narkhede on Siltuximab for CRS and ICANS in Hematologic Malignancies