Viable CAR T-cells remain detectable in cerebrospinal fluid in patients with grade ≥3 ICANS despite corticosteroid therapy.

BACKGROUND

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a severe complication of CAR T-cell therapy. Although CAR T-cells have been detected in cerebrospinal fluid (CSF), their viability remains unknown.

METHODS

We retrospectively analyzed all patients with grade ≥3 ICANS after commercial CAR T-cell therapy (February 2022 - September 2025) who underwent lumbar puncture (n=13). CSF was analyzed by flow cytometry including 7-AAD staining for CAR T-cell viability. Viable CAR T-cells were defined as CAR+CD3+7-AAD- lymphocytes. A systematic literature review identified published cases with CSF CAR T-cell detection.

RESULTS

Among 133 CAR T-cell recipients, 28 developed grade ≥3 ICANS and 13 underwent lumbar puncture (total 22 samples). Viability testing was feasible in 11 samples; all contained viable CAR T-cells (median 75%, range 27-99%), which remained detectable up to day +98 despite corticosteroid therapy. Median CSF CAR T-cell count was 4.3/µL (IQR 1.7-18.1). Protein and albumin were elevated in most patients, indicating blood-CSF barrier disruption. A literature review identified 17 published cases reporting CSF findings after CAR T-cell therapy.

CONCLUSION

To our knowledge, this is the first study demonstrating that CAR T-cells in the CSF are viable and remain detectable despite corticosteroid therapy. These findings demonstrate the presence of viable CAR T cells in the CSF of patients with ICANS and warrant prospective functional studies.