Paola Tacchetti (Italy)
Institute of Hematology “L. and A. Seragnoli“ Department of Experimental Diagnostic and Specialty MedicineAuthor Of 1 Presentation
NEUROTOXICITY-RELATED TO CAR-T THERAPY: PROPOSED PROTOCOL AND PRELIMINARY DATA FROM BOLOGNA
- Umberto Pensato (Italy)
Abstract
Background and Aims:
Chimeric antigen receptor (CAR) T-cells therapy is an effective treatment for haematological malignancies, yet hampered by cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS)1, a neuropsychiatric syndrome whose biological underpinnings are still unravelled2,3. We present our neurological protocol to manage ICANS and preliminary data.
Methods:
From September 2019 to March 2021, we recruited patients affected by refractory B-cells lymphoma (DLBCL) or multiple myeloma (MM) who received CAR-T therapy. Patients were comprehensively screened (neurological examination, EEG, brain MRI, electroneurography, neuropsychological tests) before infusion and prophylactic anti-epileptic treatment was started. From the day of CAR-T infusion, patients underwent serial neurological/instrumental examinations to monitor development of neurotoxicity. Treatment was based on ICANS severity and consisted in high-doses IV corticosteroids, variably associated with anti-cytokines antibodies.
Results:
Among 31 CAR T-cells infused patients (26 DLBCL; nine females, median age 57±16 years), 84% (n=26) patients developed CRS (median duration 4±2 days). None MM, but 38% (n=10) DLBCL patients developed ICANS (four severe; six preceded by CRS; median duration was 10±8 days). Earliest symptoms included headache, ideo-motor slowing and reduced speech fluency. Dysgraphia followed by a rapid evolution to a severe encephalopathy occurred in three cases. Brain MRI was unremarkable. EEG showed predominant frontal slowing in all cases. One patient developed refractory neurotoxicity with multifocal brain oedema, eventually dying at day 16, whereas other patients recovered.
Conclusions:
We report the first Italian data on ICANS, confirming its high incidence in DLBCL. Frequent clinical/instrumental assessment was essential to recognize early signs of neurotoxicity and promptly start appropriate treatment.