University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope, Duarte, CA.
Clin Lymphoma Myeloma Leuk. 2022 Sep;22(9):690-701. doi: 10.1016/j.clml.2022.04.025. Epub 2022 May 23.
This study estimated the comparative efficacy of ciltacabtagene autoleucel (cilta-cel; CARTITUDE-1), a chimeric antigen receptor (CAR)-T-cell therapy, versus 3 non-CAR-T therapies (belantamab mafodotin [DREAMM-2], selinexor plus dexamethasone [STORM Part 2], and melphalan flufenamide plus dexamethasone [HORIZON]), each with distinct mechanisms of action, for the treatment of patients with relapsed or refractory multiple myeloma (RRMM) who were triple-class exposed to an immunomodulatory drug, proteasome inhibitor, and an anti-CD38 monoclonal antibody.
Pairwise matching-adjusted indirect treatment comparisons (MAICs) were conducted using patient-level data for cilta-cel from CARTITUDE-1 and summary level data for each comparator (2.5 mg/kg cohort in DREAMM-2, modified intention-to-treat population in STORM Part 2, and triple-class refractory patients in HORIZON). Treated patients from CARTITUDE-1 who satisfied the eligibility of the comparator trial were included. MAICs adjusted for imbalances in important prognostic factors between CARTITUDE-1 and the comparator populations. Comparative efficacy of cilta-cel versus each therapy was estimated for overall response rate, complete response or better rate, progression-free survival, and overall survival.
After adjustment, patients treated with cilta-cel demonstrated at least a 3.1-fold and at least a 10.3-fold increase in the likelihood of achieving an overall response or complete response or better, respectively, at least a 74% reduction in the risk of disease progression or death, and at least a 47% reduction in the risk of death. These results were statistically significant.
Cilta-cel showed improved efficacy over each comparator for all outcomes, demonstrating its potential as an efficacious treatment for patients with triple-class exposed RRMM.
本研究评估了嵌合抗原受体（CAR）-T 细胞疗法 cilta-cel（cilta-cel；CARTITUDE-1）与 3 种非 CAR-T 疗法（belantamab mafodotin [DREAMM-2]、selinexor 联合地塞米松 [STORM 第 2 部分] 和 melphalan flufenamide 联合地塞米松 [HORIZON]）的疗效比较，这些疗法的作用机制不同，用于治疗三药暴露（免疫调节剂、蛋白酶体抑制剂和抗 CD38 单克隆抗体）的复发/难治性多发性骨髓瘤（RRMM）患者。
使用 CARTITUDE-1 中 cilta-cel 的患者水平数据和每个对照药物的汇总水平数据（DREAMM-2 中 2.5 mg/kg 队列、STORM 第 2 部分的改良意向治疗人群和 HORIZON 中的三药难治患者）进行了配对匹配调整间接治疗比较（MAIC）。CARTITUDE-1 中符合对照试验纳入标准的治疗患者被纳入。MAIC 调整了 CARTITUDE-1 人群和对照人群之间重要预后因素的不平衡。通过总体缓解率、完全缓解或更好率、无进展生存期和总生存期来估计 cilta-cel 与每种治疗方法的疗效比较。
调整后，接受 cilta-cel 治疗的患者在获得总体缓解或完全缓解或更好方面的可能性分别至少增加了 3.1 倍和至少增加了 10.3 倍，疾病进展或死亡的风险降低了至少 74%，死亡风险降低了至少 47%。这些结果具有统计学意义。
与每个对照药物相比，cilta-cel 在所有结果上均显示出更好的疗效，表明其作为三药暴露 RRMM 患者有效治疗方法的潜力。
