Clinical Report: Detectable Viable CAR T-cells in CSF of ICANS Patients

Overview

This study demonstrates the presence of viable CAR T-cells in the cerebrospinal fluid (CSF) of patients experiencing grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS) despite corticosteroid treatment. Viable CAR T-cells were detected in all analyzed samples, indicating their persistence in the CNS.

Background

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a serious complication of CAR T-cell therapy, which can lead to significant neurological symptoms. Understanding the viability of CAR T-cells in the CSF is crucial, as it may influence treatment strategies and patient outcomes. This study addresses a gap in knowledge regarding the biological behavior of CAR T-cells in the CNS during severe neurotoxicity.

Data Highlights

Key Findings

• 28 out of 133 CAR T-cell recipients developed grade ≥3 ICANS.
• All analyzed CSF samples contained viable CAR T-cells.
• Viable CAR T-cells remained detectable despite corticosteroid therapy.
• Median viability of CAR T-cells in CSF was 75%.
• Elevated protein and albumin levels indicated blood–CSF barrier disruption in most patients.

Clinical Implications

The detection of viable CAR T-cells in the CSF of patients with severe ICANS suggests that corticosteroid treatment may not eliminate these cells, which could contribute to ongoing neuroinflammation. Clinicians should consider the implications of persistent CAR T-cells in the CNS when managing ICANS and may need to explore alternative therapeutic strategies.

Conclusion

This study highlights the viability of CAR T-cells in the CSF of patients with grade ≥3 ICANS, emphasizing the need for further research into the role of these cells in neurotoxicity and potential treatment approaches.

Related Resources & Content

1. Blood Cancer Journal, 2022 -- Seizures and Status Epilepticus in Neurotoxicity Syndrome Associated with Immune Effector Cells (ICANS)
2. Bone Marrow Transplantation, 2025 -- Cytokine Profiling of Serum and CSF for Assessing ICANS Risk in CD19 CAR-T Treatment
3. Blood Cancer Journal, 2025 -- Development of chronic inflammatory demyelinating polyneuropathy (CIDP) following cilta-cel treatment
4. Anticytokine Therapy and Corticosteroids for Cytokine Release Syndrome and for Neurotoxicity Following T-Cell Engager or CAR T-Cell Therapy - NCBI Bookshelf
5. Frontiers, 2026 -- Viable CAR T-cells remain detectable in cerebrospinal fluid in patients with grade ≥3 ICANS despite corticosteroid therapy
6. Blood Cancer Journal — CAR-T Cells Targeting CD5 with a tEGFR Safety Mechanism Demonstrate Effective Toxicity Management
7. Clinical guidance on ICANS management
8. Frontiers | Viable CAR T-cells remain detectable in cerebrospinal fluid in patients with grade ≥3 ICANS despite corticosteroid therapy
9. Toxicities associated with CAR-T therapy compared with standard treatments in hematologic malignancies: a systematic review and meta-analysis - PMC