P008 | Prophylaxis With Levetiracetam Offers No Benefit in Cd19 Car-t for Lbcl: a Multicenter Propensity-matched Study
Year: 2025
Type: article
Abstract: Background: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common complication of CAR-T cell therapy, with a complex pathophysiology that remains only partially understood. The use of prophylactic antiepileptic drugs—particularly levetiracetam (LVT)—is widespread despite limited evidence of benefit and non-harmonized recommendations. This study aimed to evaluate the real-world impact of prophylactic LVT on the incidence and severity of ICANS. Methods and Results: We conducted a multicenter, observational, case-control study including adult patients with LBCL with CAR-T therapy across 2 Italian and 1 French centers from 2019 to 2023. Patients were divided into two cohorts based on whether they received standard LVT prophylaxis (Rome) or not (Paris). Propensity score matching (1:1) was used to balance key baseline characteristics, including disease type, CAR-T product, and inflammatory biomarkers. The primary endpoint was the incidence of ICANS of any grade. Secondary endpoints included ICANS severity, inflammatory complications, hematologic toxicity, and survival outcomes. Of the 393 patients with LBCL, 254 were analyzed after propensity score matching resulting in two well balanced groups for all variables (127 LVT-no, 127 LVT-yes). We observed no significant difference in the occurrence of ICANS of any grade between the two groups (32.3% in LVT-no vs. 37.1% in LVT-yes, p=0.29), or in severe ICANS (grades 2-4: 15.1% vs 16.1%, p=0.80; grade 3-4: 7.9% vs 9.7%, p=0.71). Clinical seizures were rare (<3%) and similarly distributed. The use of LVT was associated with a higher incidence of early immune effector cell–associated hematotoxicity (ICAHT), with grade 2-4 ICAHT occurring in 37.3% vs. 63.9% (p<0.001) of patients in the LVT-no and LVT-yes groups, respectively. Overall survival and progression-free survival did not differ significantly between the two groups (p=0.337 and 0.670). Non-relapse mortality rates were comparable (p=0.77). Conclusions: Prophylactic LVT did not reduce the incidence or severity of ICANS in this large, real-world cohort of CAR-T recipients. These findings, consistent with recent neurophysiological studies suggesting that ICANS is primarily a neuroinflammatory rather than epileptic phenomenon, question the routine use of antiepileptic prophylaxis. Moreover, LVT may be associated with increased hematologic toxicity and treatment burden.
Authors: E. Galli, R. Di Blasi, A. Di Rocco, C. Cristinelli, I. Pansini, C. Bommier, A. Corrente, I. De Bernardis, M. Viscovo, S. Hohaus, A. Modoni, F. Sorà, M. Martelli, C. Thieblemont, S. Sica
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093122192
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