嵌合抗原受体T细胞疗法用于复发或难治性大B细胞淋巴瘤三线及后续治疗的匹配调整间接治疗比较：利妥昔单抗与替沙格赛定。
Matching-adjusted indirect treatment comparison of chimeric antigen receptor T-cell therapies for third-line or later treatment of relapsed or refractory large B-cell lymphoma: lisocabtagene maraleucel versus tisagenlecleucel.
作者信息
Cartron Guillaume, Fox Christopher P, Liu Fei Fei, Kostic Ana, Hasskarl Jens, Li Daniel, Bonner Ashley, Zhang Yixie, Maloney David G, Kuruvilla John
机构信息
Montpellier University Hospital Center, 80 Avenue Augustin Fliche, Montpellier, France.
Nottingham University Hospitals NHS Trust, Nottingham, UK.
出版信息
Exp Hematol Oncol. 2022 Mar 25;11(1):17. doi: 10.1186/s40164-022-00268-z.
BACKGROUND
There are no head-to-head clinical studies comparing chimeric antigen receptor (CAR) T-cell therapies for the treatment of relapsed or refractory aggressive large B-cell lymphomas. Naive, indirect comparisons may be inappropriate, as the study designs and patient populations could differ substantially. Matching-adjusted indirect comparisons (MAIC) can reduce many biases associated with indirect comparisons between studies. To determine the comparative efficacy and safety of lisocabtagene maraleucel (liso-cel) to tisagenlecleucel, we describe an unanchored MAIC of the pivotal studies TRANSCEND NHL 001 (TRANSCEND; NCT02631044; liso-cel) and JULIET (NCT02445248; tisagenlecleucel).
METHODS
Individual patient data (IPD) from TRANSCEND were available to the authors; for the JULIET pivotal study, summary-level data from the published study were used. To balance the populations between two studies, IPD from TRANSCEND were adjusted to match the marginal distribution (e.g., mean, variance) of clinical factors among patients from JULIET.
RESULTS
Results from the primary MAIC showed liso-cel had statistically significant greater efficacy than tisagenlecleucel (objective response rate: odds ratio [OR] = 2.78, 95% confidence interval [CI]: 1.63‒4.74; complete response rate: OR = 2.01, 95% CI: 1.22‒3.30; progression-free survival: hazard ratio [HR] = 0.65, 95% CI: 0.47‒0.91; overall survival: HR = 0.67, 95% CI: 0.47‒0.95). MAIC of safety outcomes showed lower ORs for all-grade and grade ≥ 3 cytokine release syndrome, and grade ≥ 3 prolonged cytopenia for liso-cel when compared with tisagenlecleucel; there were no statistically significant differences detected for other safety outcomes.
CONCLUSIONS
Overall, this MAIC of two CAR T-cell therapies indicates liso-cel had favorable efficacy and a comparable or better safety profile relative to tisagenlecleucel.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov identifiers: NCT02631044 and NCT02445248.
背景
尚无头对头的临床研究比较嵌合抗原受体（CAR）T细胞疗法治疗复发或难治性侵袭性大B细胞淋巴瘤的疗效。单纯的间接比较可能并不合适，因为研究设计和患者群体可能存在很大差异。匹配调整间接比较（MAIC）可以减少与研究间间接比较相关的许多偏差。为了确定利妥昔单抗（liso-cel）与替沙罗汀（tisagenlecleucel）的相对疗效和安全性，我们描述了关键研究TRANSCEND NHL 001（TRANSCEND；NCT02631044；liso-cel）和JULIET（NCT02445248；tisagenlecleucel）的非锚定MAIC。
方法
作者可获取TRANSCEND的个体患者数据（IPD）；对于JULIET关键研究，使用已发表研究的汇总数据。为平衡两项研究的人群，对TRANSCEND的IPD进行调整，以匹配JULIET患者临床因素的边际分布（如均值、方差）。
结果
主要MAIC结果显示，liso-cel的疗效在统计学上显著优于tisagenlecleucel（客观缓解率：优势比[OR]=2.78，95%置信区间[CI]：1.63‒4.74；完全缓解率：OR=2.01，95%CI：1.22‒3.30；无进展生存期：风险比[HR]=0.65，95%CI：0.47‒0.91；总生存期：HR=0.67，95%CI：0.47‒0.95）。安全性结果的MAIC显示，与tisagenlecleucel相比，liso-cel所有级别和≥3级细胞因子释放综合征以及≥3级长期血细胞减少的OR较低；其他安全性结果未检测到统计学显著差异。
结论
总体而言，这两种CAR T细胞疗法的MAIC表明，相对于tisagenlecleucel，liso-cel具有良好的疗效和相当或更好的安全性。
临床试验注册
ClinicalTrials.gov标识符：NCT02631044和NCT02445248。
Zotero 插件