既往 Inotuzumab Ozogamicin 治疗对 B 细胞 ALL 成人患者 Brexucabtagene Autoleucel 结果的影响。
Impact of Prior Inotuzumab Ozogamicin Treatment on Brexucabtagene Autoleucel outcomes in Adults with B-cell ALL.
发表日期：2024 Aug 02
作者：
Ibrahim Aldoss, Gregory W Roloff, Rawan G Faramand, Noam E Kopmar, Chenyu Lin, Anjali S Advani, Simone E Dekker, Vishal K Gupta, Timothy E O'Connor, Nikeshan Jeyakumar, Ibrahim N Muhsen, Yannis K Valtis, Amy Zhang, Katharine Miller, Katherine C Sutherland, Kaitlyn C Dykes, Mohamed Ahmed, Evan C Chen, Hector Zambrano, Danielle Bradshaw, Santiago Mercadal, Marc S Schwartz, Sean I Tracy, Bhagirathbhai Dholaria, Michal Jakub Kubiak, Akash Mukherjee, Navneet S Majhail, Minoo Battiwalla, Luke Mountjoy, Shahbaz A Malik, John Mathews, Paul J Shaughnessy, Aaron Logan, Abdullah Ladha, Maryann Stefan, Caitlin Guzowski, Rasmus T Hoeg, Talal Hilal, Jozal Moore, Matthew Connor, Kristen M O'Dwyer, LaQuisa C Hill, Stephanie B Tsai, Joshua P Sasine, Melhem M Solh, Catherine J Lee, Vamsi Kota, Divya Koura, Muthu Veeraputhiran, Betsy Blunk, Caspian Oliai, Jessica T Leonard, Noelle V Frey, Jae H Park, Marlise R Luskin, Veronika Bachanova, Ahmed Galal, Michael R Bishop, Wendy Stock, Ryan D Cassaday, Vinod A Pullarkat, Bijal D Shah, Lori Muffly
来源：
Blood Advances
摘要：
先前的伊珠单抗奥佐米星 (InO) 治疗对 brexucabtagene autoleucel (brexu-cel) 成人急性淋巴细胞白血病 (ALL) 结局的影响仍不清楚，特别是对先前 InO 反应和给药时间的影响。我们对 189 名接受 brexu-cel 治疗的复发/难治性 (r/r) ALL 患者进行了回顾性多中心分析。超过一半的患者在 brexu-cel 之前接受了 InO（InO 暴露）。 InO暴露的患者接受了更严格的预处理（p = 0.02），并且在血浆分离术前经常患有活动性骨髓疾病（p = 0.03）。 brexu-cel 后的反应率和毒性特征对于 InO-暴露和 InO-naïve 具有可比性；然而，在未接受 InO 治疗的患者中，brexu-cel 缓解后巩固治疗的使用率较高 (p = 0.005)。中位随访时间为 11.4 个月，在单变量分析中，InO 暴露患者的无进展生存期 (PFS) (p=0.013) 和总生存期 (OS) (p=0.006) 较差；然而，在多变量模型中，先前的 InO 暴露并不影响 PFS（HR 1.20，95% CI，0.71-2.03）。当根据先前的 InO 反应对 InO 暴露患者进行分层时，相对于 InO 难治性患者，InO 反应者具有更好的 PFS (p=0.002) 和 OS (p<0.0001)。给予 InO 的时机并不影响 brexu-cel 的结果，接受 InO 作为桥接治疗或预血浆分离术的患者具有相当的 PFS (p=0.51) 和 OS (p=0.86)。总之，虽然在未经调整的分析中，InO 暴露与 brexu-cel 后较差的生存结果相关，但这些关联在多变量分析中不再显着，表明 InO 不太可能对 brexu-cel 疗效产生负面影响。相反，我们的数据表明，暴露于 InO 的 brexu-cel 接受者往往是具有内在不良白血病生物学的高风险患者。版权所有 © 2024 美国血液学会。
The effect of prior inotuzumab ozogamicin (InO) treatment on brexucabtagene autoleucel (brexu-cel) outcomes remains unclear in adults with acute lymphoblastic leukemia (ALL), particularly the influence off previous InO response and the timing of administration. We conducted a retrospective multicenter analysis of 189 patients with relapsed/refractory (r/r) ALL treated with brexu-cel. Over half of the patients received InO before brexu-cel (InO-exposed). InO-exposed patients were more heavily pretreated (p= 0.02) and frequently had active marrow disease pre-apheresis (p= 0.03). Response rate and toxicity profile following brexu-cel were comparable for InO-exposed and InO-naïve; however, consolidation therapy post brexu-cel response was utilized at a higher rate in InO-naïve patients (p= 0.005). With a median follow up of 11.4 months, InO-exposed patients had inferior progression-free survival (PFS) (p=0.013) and overall survival (OS) (p=0.006) in univariate analyses; however, prior InO exposure did not influence PFS (HR 1.20, 95%CI, 0.71-2.03) in multivariate models. When InO-exposed patients were stratified according to prior InO response, InO responders had superior PFS (p=0.002) and OS (p<0.0001) relative to InO-refractory. The timing of administering InO did not affect brexu-cel outcomes, with comparable PFS (p=0.51) and OS (p=0.86) for patients receiving InO as bridging therapy or pre-apheresis. In conclusion, while InO exposure was associated with inferior survival outcomes following brexu-cel in unadjusted analyses, these associations were no longer significant in multivariate analyses, suggesting it is unlikely that InO negatively impacts brexu-cel efficacy. Our data instead imply that InO-exposed recipients of brexu-cel tend to be higher-risk patients with intrinsic adverse leukemia biology.Copyright © 2024 American Society of Hematology.