brexucabtagene autoleucel 在伴中枢神经系统受累的复发/难治性急性淋巴细胞白血病患者中的结局

Patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) with central nervous system (CNS) involvement (CNS B-ALL) have poor outcomes and were frequently excluded from CD19-targeting chimeric antigen receptor (CAR) T-cell clinical trials. The efficacy and safety of brexucabtagene autoleucel (brexu-cel) in adults with R/R B-ALL was established by the ZUMA-3 trial, which excluded patients with advanced or symptomatic CNS involvement.

In this retrospective multicenter analysis, we investigated the safety and efficacy of brexu-cel in patients with CNS B-ALL using data from the ROCCA (Real-World Outcomes Collaborative for CAR T in ALL) consortium.

Of 189 patients who received infusion, 31 had CNS-2 (presence of blasts in cerebrospinal fluid with <5 white blood cells [WBCs] per L) or CNS-3 (presence of blasts with >5 WBCs per L and/or clinical signs/symptoms) disease before apheresis and are the focus of this report. The median age was 46. 5 years (range, 24-76), and 58. 1% were male. Most (87. 1%) received bridging therapy. After brexu-cel, 21 of 24 patients with CNS restaging (87. 5%) achieved CNS-1.

Additionally, 28 of 30 evaluable patients achieved marrow complete remission; 25 were measurable residual disease negative. No statistically significant differences were seen in progression-free survival or overall survival after brexu-cel among patients with or without CNS involvement. Similarly, grade 3/4 immune effector cell-associated neurotoxicity syndrome occurred similarly in patients with (35. 5%) and without (30%) CNS disease.

In conclusion, our data suggest that brexu-cel results in high response rates in patients with CNS B-ALL, with toxicity comparable with that in patients without CNS involvement.