Send to

Choose Destination
Blood. 2019 May 16;133(20):2212-2221. doi: 10.1182/blood-2018-12-893396. Epub 2019 Feb 26.

Clinical presentation, management, and biomarkers of neurotoxicity after adoptive immunotherapy with CAR T cells.

Author information

Division of Neuro-Oncology, Department of Neurology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA.
Department of Neurology, Yale School of Medicine, New Haven, CT.
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; and.
Cellular Immunotherapy Program and.
Hematology & Oncology Division, Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA.


Chimeric antigen receptor (CAR) T cells have emerged as a promising class of cell-based immunotherapy in refractory malignancies. Neurotoxicity represents a common and potentially life-threatening adverse effect of CAR T cells, and clinical experience is limited. Here, we describe the clinical presentation and management of 25 adult patients who presented with neurotoxic syndromes after CAR T-cell therapy at the Massachusetts General Hospital. This cohort includes 24 patients treated with CD19-directed CAR T cells for non-Hodgkin lymphoma (n = 23) and acute lymphoblastic leukemia (n = 1), and 1 patient treated with α-fetoprotein-directed CAR T cells for hepatocellular carcinoma (n = 1). Twelve of the 25 patients (48%) developed grade 1-2 neurotoxicity and 13 patients (52%) presented with grade 3-4 neurotoxicity. We found that lower platelet counts at time of CAR T-cell infusion were associated with more severe neurotoxicity (P = .030). Cytokine release syndrome occurred in 24 of 25 patients (96%). Serum levels of ferritin peaked with onset of neurologic symptoms, and higher ferritin levels were associated with higher neurotoxicity grade. Grade 3-4 neurotoxicity correlated negatively with overall survival (OS) (P = .013). Median OS of the entire cohort was 54.7 weeks. Eight patients (32%) with grade 3-4 neurotoxicity were deceased at database closure, whereas none died with neurotoxicity grade 1-2. High pretreatment lactate dehydrogenase was frequently encountered in lymphoma patients with grade 3-4 neurotoxicity and correlated negatively with progression-free survival (P = .048). We did not find evidence that steroid use ≥7 days altered the patient's outcome when compared with <7 days of steroids. Management of CAR T cell-mediated neurotoxicity warrants evaluation in prospective clinical trials.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center