Martin Thomas, Krishnan Amrita, Yong Kwee, Weisel Katja, Mehra Maneesha, Nair Sandhya, Qi Keqin, Londhe Anil, Diels Joris, Crivera Concetta, Jackson Carolyn C, Olyslager Yunsi, Vogel Martin, Schecter Jordan M, Banerjee Arnob, Valluri Satish, Usmani Saad Z, Berdeja Jesus G, Jagannath Sundar
UCSF Helen Diller Family Comprehensive Cancer Center San Francisco California USA.
Judy and Bernard Briskin Center for Multiple Myeloma Research Duarte California USA.
EJHaem. 2021 Dec 10;3(1):97-108. doi: 10.1002/jha2.312. eCollection 2022 Feb.
Ciltacabtagene autoleucel (cilta-cel) is a novel chimeric antigen receptor T-cell therapy that is being evaluated in the CARTITUDE-1 trial (NCT03548207) in patients with relapsed or refractory multiple myeloma (RRMM) who received as part of their previous therapy an immunomodulatory drug, proteasome inhibitor, and an anti-CD38 monoclonal antibody (i.e., triple-class exposed). Given the absence of a control arm in CARTITUDE-1, this study assessed the comparative effectiveness of cilta-cel and physician's choice of treatment (PCT) using an external real-world control arm from the Flatiron Health multiple myeloma cohort registry.
Given the availability of individual patient data for cilta-cel from CARTITUDE-1 and PCT in Flatiron, inverse probability of treatment weighting was used to adjust for unbalanced baseline covariates of prognostic significance: refractory status, cytogenetic profile, International Staging System stage, time to progression on last regimen, number of prior lines of therapy, years since diagnosis, and age. Comparative effectiveness was estimated for progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS). A range of sensitivity analyses were conducted.
Baseline characteristics were similar between the two cohorts after propensity score weighting. Patients with cilta-cel had improved PFS (HR: 0.18 [95% CI: 0.12, 0.27; < 0.0001]), TTNT (HR: 0.15 [95% CI: 0.09, 0.22; < 0.0001]), and OS (HR: 0.25 [95% CI: 0.13, 0.46; < 0.0001]) versus PCT. Cilta-cel treatment benefit was robust and consistent across all sensitivity analyses.
Cilta-cel demonstrated significantly superior effectiveness over PCT for all outcomes, highlighting its potential as an effective therapy in patients with triple-class exposed RRMM.
西达基奥仑赛（cilta-cel）是一种新型嵌合抗原受体T细胞疗法，正在CARTITUDE-1试验（NCT03548207）中对复发或难治性多发性骨髓瘤（RRMM）患者进行评估，这些患者在先前治疗中接受过免疫调节药物、蛋白酶体抑制剂和抗CD38单克隆抗体（即接受过三类药物治疗）。鉴于CARTITUDE-1试验中没有对照组，本研究使用来自Flatiron Health多发性骨髓瘤队列登记处的外部真实世界对照组，评估了西达基奥仑赛与医生选择的治疗方法（PCT）的相对有效性。
鉴于可获得CARTITUDE-1试验中西达基奥仑赛以及Flatiron中PCT的个体患者数据，采用治疗权重逆概率法对具有预后意义的不平衡基线协变量进行调整：难治状态、细胞遗传学特征、国际分期系统分期、上一治疗方案的无进展时间、既往治疗线数、诊断后年限和年龄。对无进展生存期（PFS）、下次治疗时间（TTNT）和总生存期（OS）的相对有效性进行了估计。进行了一系列敏感性分析。
倾向评分加权后，两个队列的基线特征相似。与PCT相比，接受西达基奥仑赛治疗的患者的PFS（风险比：0.18 [95%置信区间：0.12，0.27；<0.0001]）、TTNT（风险比：0.15 [95%置信区间：0.09，0.22；<0.0001]）和OS（风险比：0.25 [95%置信区间：0.13，0.46；<0.0001]）均有所改善。在所有敏感性分析中，西达基奥仑赛的治疗益处均稳健且一致。
在所有结局方面，西达基奥仑赛均显示出显著优于PCT的有效性，突出了其作为接受过三类药物治疗的RRMM患者有效疗法的潜力。
