预防性阿那白滞素预防侵袭性 B 细胞淋巴瘤 CAR-T 细胞治疗后神经毒性：单中心真实世界经验

Background/Objectives : Chimeric antigen receptor T-cell (CAR T) therapy is an effective treatment for relapsed/refractory (r/r) aggressive B-cell lymphomas; however, acute toxicities, such as immune effector cell-associated neurotoxicity syndrome (ICANS), remain common. Interleukin-1 (IL-1) has been implicated in the pathogenesis of ICANS, suggesting that prophylactic anakinra, an IL-1 receptor antagonist, might reduce its incidence or severity. Methods : We retrospectively analyzed 80 patients with B-cell lymphomas who received CD19-directed CAR T-cell therapy (tisagenlecleucel, axicabtagene ciloleucel, or lisocabtagene maraleucel) at the Bern University Hospital between April 2019 and June 2022. One cohort received prophylactic anakinra (100 mg subcutaneously on days 0 to +6 post-infusion), while the comparison cohort did not. Results : The incidence of ICANS was similar between groups (14 patients, 35%) with anakinra vs.

10 (25%) in the standard cohort ( p = 0. 464). Rates of grade 3 ICANS were also comparable (eight (20%) vs. seven (18%), p > 0. 999). Among patients who developed ICANS, median hospitalization was numerically shorter with anakinra (27 vs. 40 days, p = 0. 077). Anakinra did not impair CAR T-cell expansion and was well tolerated, with no treatment-related adverse events. Survival outcomes, including overall survival (OS) and progression-free survival (PFS), were similar between cohorts.

Conclusions : In summary, prophylactic anakinra did not reduce the incidence or severity of ICANS in our analysis; however, it may be associated with shorter hospitalization in affected patients. Whether this reflects a direct therapeutic effect or improved overall toxicity management remains uncertain. Larger prospective studies are warranted to further clarify the role of anakinra for prophylactic treatment of ICANS following CAR T-cell therapy.