학술논문
CAR t-cell therapy in BOlogNa–NEUrotoxicity TReatment and Assessment in Lymphoma (CARBON–NEUTRAL): proposed protocol and results from an Italian study.
Document Type
Article
Author
Pensato, Umberto; Amore, Giulia; Muccioli, Lorenzo; Sammali, Susanna; Rondelli, Francesca; Rinaldi, Rita; D'Angelo, Roberto; Nicodemo, Marianna; Mondini, Susanna; Sambati, Luisa; Asioli, Gian Maria; Rossi, Simone; Santoro, Rossella; Cretella, Lucia; Ferrari, Susy; Spinardi, Luca; Faccioli, Luca; Fanti, Stefano; Paccagnella, Andrea; Pierucci, Elisabetta
Source
Subject
*CANCER treatment
*T cells
*FRONTAL lobe
*CEREBRAL edema
*FRONTAL lobe diseases
*NON-Hodgkin's lymphoma
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Language
ISSN
0340-5354
Abstract
Objective: To investigate neurotoxicity clinical and instrumental features, incidence, risk factors, and early and long-term prognosis in lymphoma patients who received CAR T-cell therapy. Methods: In this prospective study, consecutive refractory B-cell non-Hodgkin lymphoma patients who received CAR T-cell therapy were included. Patients were comprehensively evaluated (neurological examination, EEG, brain MRI, and neuropsychological test) before and after (two and twelve months) CAR T-cells. From the day of CAR T-cells infusion, patients underwent daily neurological examinations to monitor the development of neurotoxicity. Results: Forty-six patients were included in the study. The median age was 56.5 years, and 13 (28%) were females. Seventeen patients (37%) developed neurotoxicity, characterized by encephalopathy frequently associated with language disturbances (65%) and frontal lobe dysfunction (65%). EEG and brain FDG-PET findings also supported a predominant frontal lobe involvement. The median time at onset and duration were five and eight days, respectively. Baseline EEG abnormalities predicted ICANS development in the multivariable analysis (OR 4.771; CI 1.081–21.048; p = 0.039). Notably, CRS was invariably present before or concomitant with neurotoxicity, and all patients who exhibited severe CRS (grade ≥ 3) developed neurotoxicity. Serum inflammatory markers were significantly higher in patients who developed neurotoxicity. A complete neurological resolution following corticosteroids and anti-cytokines monoclonal antibodies was reached in all patients treated, except for one patient developing a fatal fulminant cerebral edema. All surviving patients completed the 1-year follow-up, and no long-term neurotoxicity was observed. Conclusions: In the first prospective Italian real-life study, we presented novel clinical and investigative insights into ICANS diagnosis, predictive factors, and prognosis. [ABSTRACT FROM AUTHOR]