Riedell Peter A, Grady Connor B, Nastoupil Loretta J, Luna Alejandro, Ahmed Nausheen, Maziarz Richard T, Hu Marie, Brower Jamie, Hwang Wei-Ting, Schuster Stephen J, Chen Andy I, Oluwole Olalekan O, Bachanova Veronika, McGurik Joseph P, Perales Miguel-Angel, Bishop Michael R, Porter David L
David and Etta Jonas Center for Cellular Therapy, University of Chicago, Chicago, IL.
Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania and Abramson Cancer Center, Philadelphia, PA.
Blood Adv. 2025 Mar 11;9(5):1232-1241. doi: 10.1182/bloodadvances.2024014164.
Lisocabtagene maraleucel (liso-cel) is an autologous CD19-directed chimeric antigen receptor T-cell therapy approved for the treatment of relapsed/refractory large B-cell lymphoma. We present a multicenter retrospective study evaluating safety, efficacy, and resource use of liso-cel in the standard-of-care setting. Patients received commercial liso-cel at 7 US medical centers, and patient selection, toxicity management, and disease assessment followed institutional practices. Among 101 patients who received infusion, the median age was 71 years (35% aged ≥75 years), 68% had a Charlson comorbidity index score of ≥3, and 10% had secondary central nervous system involvement. Median number of prior therapies was 3; and because of comorbidities, 33% would have been ineligible for the TRANSCEND study. Bridging therapy was used in 60% (43% received polatuzumab-based treatment). Any-grade cytokine-release syndrome occurred in 49% (3% grade ≥3) with any-grade immune effector cell-associated neurotoxicity syndrome occurring in 26% (10% grade ≥3). The overall response rate (ORR) to bridging therapy was 45%, with 18% achieving a complete response (CR). Following liso-cel infusion, the day 90 ORR was 66% (60% CR); and with a median follow-up of 15.5 months, 12-month progression-free survival (PFS) and overall survival (OS) were 55% and 68%, respectively. A normal lactate dehydrogenase level before lymphodepletion was associated with improved PFS and OS. These analyses confirm similar efficacy and safety of commercial liso-cel compared with pivotal trial results. Notably, these outcomes were achieved in patients predominantly of advanced age and with significant comorbidities. Results also likely reflect advancements in patient selection, toxicity management, and the use of novel bridging strategies.
利妥昔单抗(liso-cel)是一种自体CD19导向的嵌合抗原受体T细胞疗法,已被批准用于治疗复发/难治性大B细胞淋巴瘤。我们开展了一项多中心回顾性研究,评估在标准治疗环境中利妥昔单抗的安全性、疗效和资源使用情况。患者在美国7家医疗中心接受了商业化的利妥昔单抗治疗,患者选择、毒性管理和疾病评估均遵循机构惯例。在101例接受输注的患者中,中位年龄为71岁(35%年龄≥75岁),68%的查尔森合并症指数评分≥3,10%有继发性中枢神经系统受累。既往治疗的中位次数为3次;由于合并症,33%的患者不符合TRANSCEND研究的入组标准。60%的患者使用了桥接治疗(43%接受了基于泊洛妥珠单抗的治疗)。49%的患者发生了任何级别的细胞因子释放综合征(3%为≥3级),26%的患者发生了任何级别的免疫效应细胞相关神经毒性综合征(10%为≥3级)。桥接治疗的总体缓解率(ORR)为45%,18%的患者达到完全缓解(CR)。利妥昔单抗输注后,第90天的ORR为66%(60%为CR);中位随访15.5个月,12个月无进展生存期(PFS)和总生存期(OS)分别为55%和68%。淋巴细胞清除前乳酸脱氢酶水平正常与PFS和OS改善相关。这些分析证实了商业化利妥昔单抗与关键试验结果相比具有相似的疗效和安全性。值得注意的是,这些结果是在主要为老年且合并症严重的患者中取得的。结果也可能反映了患者选择、毒性管理和新型桥接策略使用方面的进展。