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Multicenter Study
. 2025 Nov 11;9(21):5501-5509.
doi: 10.1182/bloodadvances.2025017378.

Routine prophylaxis with levetiracetam offers no benefit in CD19 CAR-T for LBCL: a multicenter propensity-matched study

Eugenio Galli  1   2 , Roberta Di Blasi  3 , Alice Di Rocco  4 , Caterina Cristinelli  3 , Ilaria Pansini  1   2 , Côme Bommier  3 , Alessandro Corrente  2 , Ilenia De Bernardis  3 , Marcello Viscovo  1   2 , Stefan Hohaus  1   2 , Anna Modoni  5 , Federica Sorà  1   2 , Patrizia Chiusolo  1   2 , Maurizio Martelli  4 , Simona Sica  1   2 , Catherine Thieblemont  3   6   7
Affiliations
Multicenter Study

Routine prophylaxis with levetiracetam offers no benefit in CD19 CAR-T for LBCL: a multicenter propensity-matched study

Eugenio Galli et al. Blood Adv. .

Abstract

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 chimeric antigen receptor T-cell (CAR-T) therapy for LBCL (large B-cell lymphoma). A propensity score-matched cohort of 254 patients was analyzed, comparing those receiving LVT prophylaxis (LTV-yes) with those not receiving it (LTV-no), in a 1:1 ratio. The results showed no significant difference in the occurrence of ICANS of any grade between the 2 groups (32.3% in LVT-no vs 37.1% in LVT-yes; P = .29), or in severe ICANS (grades 2-4, 15.1% vs 16.1% [P = .80]; grade 3-4, 7.9% vs 9.7% [P = .71]). The use of LVT was associated with a higher incidence of early immune effector cell-associated hematotoxicity (ICAHT), with grade 2 to 4 ICAHT occurring in 37.3% vs 63.9% (P < .001) of patients in the LVT-no and LVT-yes groups, respectively. Overall survival and progression-free survival did not differ significantly between the 2 groups (P = .337 and .670). Nonrelapse mortality rates were comparable (P = .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 after ICANS treatment.

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Conflict of interest statement

Conflict-of-interest disclosure: E.G. received travel grants from, and/or participated in speakers bureau for, Novartis, Bristol Myers Squibb (BMS), and Kite/Gilead. C.B. has received advisory fees from Johnson and Johnson and BMS. R.D.B. reports honoraria for board membership and conference attendance and travel grants from Roche, Kite/Gilead, Novartis, and BMS. C.T. reports honoraria for board membership and conference attendance and travel grants from Roche, Kite/Gilead, Novartis, and BMS. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Risk factors for ICANS. (A) Incidence and grading of ICANS according to the different prophylactic strategies (with or without LVT). (B) Risk factors for ICANS of any grade in univariate analysis (forest plot). ASCT, autologous hematopoietic stem cell transplantation; CR, complete response; DLBCL, diffuse large B-cell lymphoma; IPI, International Prognostic Index; ECOG, Eastern Cooperative Oncology Group performance status scale; PD, progressive disease; PMBL, primary mediastinal BCL; PR, partial response; SD, stable disease; tFL, transformed follicular lymphoma; tisa-cel, tisagenlecleucel.
Figure 2.
Figure 2.
Non-relapse mortality and relapse. Cumulative incidence of NRM (A) and relapse (B) after CAR-T therapy by antiepileptic prophylaxis with LVT. The type of strategy does not influence NRM or relapse rate.
See this image and copyright information in PMC

References

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