Muhsen Ibrahim N, Roloff Gregory W, Faramand Rawan, Othman Tamer, Valtis Yannis, Kopmar Noam E, Dekker Simone E, Connor Matthew, Mercadal Santiago, O'Connor Timothy E, Dykes Kaitlyn C, Ahmed Mohamed, Jeyakumar Nikeshan, Zhang Amy, Miller Katharine, Sutherland Katherine C, Guzowski Caitlin, Gupta Vishal K, Majhail Navneet, Battiwalla Minoo, Solh Melhem M, Malik Shahbaz A, Mathews John, Oliai Caspian H, Shaughnessy Paul, Mountjoy Luke, Lee Catherine J, Logan Aaron C, Tsai Stephanie B, Leonard Jessica T, Schwartz Marc, Sasine Joshua P, Kumaran Muthu, Frey Noelle, Park Jae H, Koura Divya, Cassaday Ryan D, Shah Bijal D, Aldoss Ibrahim, Muffly Lori S, Hill LaQuisa C
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital, Houston, TX.
Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL.
Blood Adv. 2025 Aug 26;9(16):4081-4089. doi: 10.1182/bloodadvances.2024015779.
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 μL) or CNS-3 (presence of blasts with >5 WBCs per μL 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.
复发/难治性（R/R）B细胞急性淋巴细胞白血病（B-ALL）合并中枢神经系统（CNS）受累（CNS B-ALL）的患者预后较差，并且经常被排除在靶向CD19的嵌合抗原受体（CAR）T细胞临床试验之外。ZUMA-3试验确定了布雷西尤单抗（brexucabtagene autoleucel，brexu-cel）在成人R/R B-ALL中的疗效和安全性，该试验排除了有晚期或有症状的CNS受累患者。在这项回顾性多中心分析中，我们使用来自ROCCA（ALL中CAR T细胞真实世界结局协作组）联盟的数据，研究了brexu-cel在CNS B-ALL患者中的安全性和疗效。在189例接受输注的患者中，31例在采集前患有CNS-2（脑脊液中存在原始细胞，每微升白细胞[WBC] <5个）或CNS-3（每微升白细胞>5个且/或有临床体征/症状的原始细胞存在）疾病，是本报告的重点。中位年龄为46.5岁（范围24 - 76岁），58.1%为男性。大多数（87.1%）接受了桥接治疗。使用brexu-cel治疗后，24例进行CNS重新分期的患者中有21例（87.5%）达到CNS-1。此外，30例可评估患者中有28例实现了骨髓完全缓解；25例微小残留病呈阴性。在有或无CNS受累的患者中，使用brexu-cel治疗后的无进展生存期或总生存期均未观察到统计学上的显著差异。同样，3/4级免疫效应细胞相关神经毒性综合征在有CNS疾病（35.5%）和无CNS疾病（30%）的患者中发生率相似。总之，我们的数据表明，brexu-cel在CNS B-ALL患者中产生了高缓解率，其毒性与无CNS受累患者相当。
