Aldoss Ibrahim, Roloff Gregory W, Faramand Rawan, Kopmar Noam E, Lin Chenyu, Advani Anjali S, Dekker Simone E, Gupta Vishal K, O'Connor Timothy E, Jeyakumar Nikeshan, Muhsen Ibrahim N, Valtis Yannis, Zhang Amy, Miller Katharine, Sutherland Katherine, Dykes Kaitlyn C, Ahmed Mohamed, Chen Evan, Zambrano Hector, Bradshaw Danielle, Mercadal Santiago, Schwartz Marc, Tracy Sean, Dholaria Bhagirathbhai, Kubiak Michal, Mukherjee Akash, Majhail Navneet, Battiwalla Minoo, Mountjoy Luke, Malik Shahbaz A, Mathews John, Shaughnessy Paul, Logan Aaron C, Ladha Abdullah, Stefan Maryann, Guzowski Caitlin, Hoeg Rasmus T, Hilal Talal, Moore Jozal, Connor Matthew, O'Dwyer Kristen M, Hill LaQuisa C, Tsai Stephanie B, Sasine Joshua, Solh Melhem M, Lee Catherine J, Kota Vamsi K, Koura Divya, Veeraputhiran Muthu, Blunk Betsy, Oliai Caspian, Leonard Jessica T, Frey Noelle V, Park Jae H, Luskin Marlise R, Bachanova Veronika, Galal Ahmed, Bishop Michael R, Stock Wendy, Cassaday Ryan D, Pullarkat Vinod, Shah Bijal D, Muffly Lori S
Division of Leukemia, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA.
Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL.
Blood Adv. 2024 Dec 10;8(23):6139-6147. doi: 10.1182/bloodadvances.2024013747.
The effect of prior inotuzumab ozogamicin (InO) treatment on brexucabtagene autoleucel (brexu-cel) outcomes remains unclear in adults with acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter analysis of 189 patients with relapsed/refractory 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 = .02) and frequently had active marrow disease before apheresis (P = .03). Response rate and toxicity profile after brexu-cel were comparable for InO-exposed and InO-naïve patients; however, consolidation therapy after brexu-cel response was used at a higher rate in InO-naïve patients (P = .005). With a median follow-up of 11.4 months, InO-exposed patients had inferior progression-free survival (PFS; P = .013) and overall survival (OS; P = .006) in univariate analyses; however, prior InO exposure did not influence PFS (hazard ratio, 1.20; 95% confidence interval, 0.71-2.03) in multivariate models. Within InO-exposed patients, InO responders had superior PFS (P = .002) and OS (P < .0001) relative to InO-refractory patients. The timing of administering InO did not affect brexu-cel outcomes, with comparable PFS (P = .51) and OS (P = .86) for patients receiving InO as bridging therapy or before apheresis. In conclusion, although InO exposure was associated with inferior survival outcomes after brexu-cel in unadjusted analyses, these associations were no longer significant in multivariate analyses, suggesting it is unlikely that InO negatively affects 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.
在成人急性淋巴细胞白血病（ALL）患者中，既往使用奥英妥珠单抗（InO）治疗对布雷西尤单抗（brexu-cel）治疗结果的影响尚不清楚。我们对189例接受brexu-cel治疗的复发/难治性ALL患者进行了一项回顾性多中心分析。超过一半的患者在接受brexu-cel治疗前接受了InO（InO暴露组）。InO暴露组患者的预处理更为密集（P = 0.02），且在采集前常有活跃的骨髓疾病（P = 0.03）。InO暴露组和未暴露组患者在接受brexu-cel治疗后的缓解率和毒性特征相当；然而，未接受InO治疗的患者在brexu-cel治疗缓解后接受巩固治疗的比例更高（P = 0.005）。中位随访11.4个月，单因素分析显示，InO暴露组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，既往InO暴露并未影响PFS（风险比，1.20；95%置信区间，0.71 - 2.03）。在InO暴露组患者中，InO治疗有反应的患者相对于InO治疗无效的患者具有更好的PFS（P = 0.002）和OS（P < 0.0001）。给予InO的时间并不影响brexu-cel的治疗结果，接受InO作为桥接治疗或在采集前接受InO治疗的患者的PFS（P = 0.51）和OS（P = 0.86）相当。总之，尽管在未经调整的分析中，InO暴露与brexu-cel治疗后的生存结果较差相关，但在多变量分析中这些关联不再显著，这表明InO不太可能对brexu-cel的疗效产生负面影响。我们的数据反而表明，接受brexu-cel治疗的InO暴露患者往往是具有内在不良白血病生物学特征的高风险患者。
