Routine Prophylaxis with Levetiracetam offers no benefit in CD19 CAR-T for LBCL: a Multicenter Propensity-matched Study Open Access

• Routine prophylaxis with levetiracetam does not reduce the risk of any grade or severe ICANS after CAR-T for LBCL

• Levetiracetam may induce deeper early immune effector cell–associated hematotoxicity (ICAHT)

This study aims to evaluate the impact of levetiracetam (LVT) prophylaxis on the incidence and severity of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) in patients undergoing anti-CD19 CAR-T therapy for large B-cell lymphoma (LBCL). A propensity score-matched cohort of 254 patients was analyzed, comparing those receiving LVT prophylaxis with those not receiving it in a 1:1 ratio. The results showed 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). 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). These findings suggest that routine use of LVT as prophylaxis for ICANS in CAR-T therapy is not effective, and further research is needed to refine its role in selected populations or post-ICANS treatment.