Intravenous Immunoglobulin (IVIG) for Patients with Severe Neurotoxicity Associated with Chimeric Antigen Receptor T-Cell (CAR-T) Therapy

Int J Mol Sci. 2025 Apr 21;26(8):3904. doi: 10.3390/ijms26083904.

Abstract

Severe immune effector cell-associated neurotoxicity syndrome (ICANS) occurs in about 30% of all patients with large B-cell lymphoma (LBCL) who are treated with axicabtagene ciloleucel (axi-cel). There are currently limited treatment strategies other than the standard corticosteroids, and it is essential to find additional therapies to manage severe ICANS. We conducted a retrospective study of neurologic outcomes among patients who received axi-cel for LBCL from May 2015 to February 2019. We identified patients who developed severe ICANS and were treated with glucocorticoids followed by intravenous immunoglobulin (IVIG) (n = 9) or glucocorticoids alone (n = 10). There was no statistically significant difference in the time to resolution (TTR) of severe ICANS between groups; however, patients in the IVIG had more severe grades of ICANS with a lower performance status at baseline. The cumulative steroid days were 11.2 in the IVIG arm and 13.5 in the glucocorticoids-only arm. The use of IVIG for severe ICANS after axi-cel therapy was tolerable and safe and is generally recommended in the CAR-T setting in patients with hypogammaglobinemia. The use of IVIG as a potential therapeutic agent for severe ICANS can be further explored in future prospective studies.

Keywords: CAR-T; CAR-T-related encephalopathy syndrome; CRES; ICANS; IVIG; axicabtagene ciloleucel; neurotoxicity.

MeSH terms

  • Adult
  • Aged
  • Biological Products
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunoglobulins, Intravenous* / therapeutic use
  • Immunotherapy, Adoptive* / adverse effects
  • Lymphoma, Large B-Cell, Diffuse* / immunology
  • Lymphoma, Large B-Cell, Diffuse* / therapy
  • Male
  • Middle Aged
  • Neurotoxicity Syndromes* / drug therapy
  • Neurotoxicity Syndromes* / etiology
  • Receptors, Chimeric Antigen*
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Immunoglobulins, Intravenous
  • Receptors, Chimeric Antigen
  • axicabtagene ciloleucel
  • Glucocorticoids
  • Biological Products