Siltuximab for chimeric antigen receptor T-cell therapy–related CRS and ICANS: a multicenter retrospective analysis

Chimeric antigen receptor T-cell (CAR-T) therapies are effective in many hematologic malignancies; however, adverse events including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) can affect a significant number of patients. Those who develop refractory CRS or ICANS have few treatment options. Siltuximab, a monoclonal antibody binding circulating interleukin-6, has been proposed to have clinical activity in both CRS and ICANS. We conducted a multicenter retrospective analysis of siltuximab treatment for CRS and ICANS after CAR-T therapy in a real-world cohort from 6 academic centers. Fifty-four patients were evaluated. Sixteen patients had CRS previously treated with tocilizumab and 17 patients had ICANS previously treated with steroids. Of the patients with CRS at the time of siltuximab, 75% had improvement in CRS grade. Of the patients with ICANS at the time of siltuximab, 60% had improvement in ICANS grade. To our knowledge, this is the largest cohort of patients treated with siltuximab for CRS and/or ICANS after CAR-T therapies. Siltuximab appeared to be effective for both CRS and ICANS, including previously treated toxicities. These data support the use of siltuximab in CRS and ICANS as well as provide rationale for future prospective studies.

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Publication Details

Journal
Blood Advances
Published
2024-10-22
DOI
https://doi.org/10.1182/bloodadvances.2024013688
Citations
28
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
7.91

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article

Siltuximab for chimeric antigen receptor T-cell therapy–related CRS and ICANS: a multicenter retrospective analysis

Marcus Geer, James Westholder, Paolo F. Caimi, David Frame et al.
28 citations
Blood Advances
CAR-T cell therapy research
7.91
article

Siltuximab for chimeric antigen receptor T-cell therapy–related CRS and ICANS: a multicenter retrospective analysis

Marcus Geer, James Westholder, Paolo F. Caimi, David Frame, Marcos de Lima, Evandro D. Bezerra, Monalisa Ghosh, Chenyu Lin, Nathan Denlinger, Justin Tossey, Qiuhong Zhao, Narendranath Epperla, Timothy J. Voorhees, Nausheen Ahmed, Ahmed Galal, Amneet Bajwa, Joeseph Maakaron
article en
28 citations

Abstract

Chimeric antigen receptor T-cell (CAR-T) therapies are effective in many hematologic malignancies; however, adverse events including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) can affect a significant number of patients. Those who develop refractory CRS or ICANS have few treatment options. Siltuximab, a monoclonal antibody binding circulating interleukin-6, has been proposed to have clinical activity in both CRS and ICANS. We conducted a multicenter retrospective analysis of siltuximab treatment for CRS and ICANS after CAR-T therapy in a real-world cohort from 6 academic centers. Fifty-four patients were evaluated. Sixteen patients had CRS previously treated with tocilizumab and 17 patients had ICANS previously treated with steroids. Of the patients with CRS at the time of siltuximab, 75% had improvement in CRS grade. Of the patients with ICANS at the time of siltuximab, 60% had improvement in ICANS grade. To our knowledge, this is the largest cohort of patients treated with siltuximab for CRS and/or ICANS after CAR-T therapies. Siltuximab appeared to be effective for both CRS and ICANS, including previously treated toxicities. These data support the use of siltuximab in CRS and ICANS as well as provide rationale for future prospective studies.

Blood AdvancesVol. 9(1)
Cleveland Clinic (US), Duke University (US), University of Michigan (US), The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US), University of Minnesota System (US), The University of Kansas Cancer Center (US), Michigan United (US), Michigan Medicine (US), Duke Medical Center (US), Cellular Therapeutics (United Kingdom) (GB), Minnesota Oncology (US), The Ohio State University (US)
National Institutes of Health, National Heart, Lung, and Blood Institute
Good health and well-being
Openalex Percentile: Top 2%
CAR-T cell therapy research
7.91
DOIOpen Access PDFOpenAlex
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