In the absence of randomized studies directly comparing chimeric antigen receptor T cell therapies, this study used matching-adjusted indirect comparisons (MAIC) to evaluate the comparative efficacy and safety of lisocabtagene maraleucel (liso-cel) versus axicabtagene ciloleucel (axi-cel) in patients with relapsed or refractory large B cell lymphoma (LBCL). Primary data sources included individual patient data from the TRANSCEND NHL 001 study (TRANSCEND [NCT02631044]; N = 256 for efficacy set, N = 269 for safety set) for liso-cel and summary-level data from the ZUMA-1 study (NCT02348216; N = 101 for efficacy set, N = 108 for safety set) for axi-cel. Inter-study differences in design, eligibility criteria, baseline characteristics, and outcomes were assessed and aligned to the extent feasible. Clinically relevant prognostic factors were adjusted in a stepwise fashion by ranked order. Since bridging therapy was allowed in TRANSCEND but not ZUMA-1, the initial efficacy and safety analyses included bridging therapy use as a matching factor (TRANSCEND patients who received bridging therapy were removed). Subsequent sensitivity analyses excluded this matching factor. The initial analysis showed similar MAIC-weighted efficacy outcomes between TRANSCEND and ZUMA-1 for overall and complete response rates (odds ratio [95% confidence interval (CI)], 1.40 [0.56–3.49] and 1.21 [0.56–2.64], respectively) and for overall survival and progression-free survival (hazard ratio [95% CI], 0.81 [0.44–1.49] and 0.95 [0.58–1.57], respectively). MAIC-weighted safety outcomes favored liso-cel, with significantly lower odds of all-grade and grade ≥ 3 cytokine release syndrome (odds ratio [95% CI], 0.03 [0.01–0.07] and 0.08 [0.01–0.67], respectively) and study-specific neurological events (0.16 [0.08–0.33] and 0.05 [0.02–0.15], respectively). Efficacy and safety outcomes remained similar in sensitivity analyses, which did not include use of bridging therapy as a matching factor. After matching and adjusting for clinically relevant prognostic factors, liso-cel demonstrated comparable efficacy and a more favorable safety profile compared with axi-cel in patients with third- or later-line relapsed or refractory LBCL. Trial registration: NCT02631044 and NCT02348216

中文翻译：

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liso-cel 与 axi-cel 在复发或难治性大 B 细胞淋巴瘤中的匹配调整间接治疗比较

在没有直接比较嵌合抗原受体 T 细胞疗法的随机研究的情况下，本研究使用匹配调整的间接比较 (MAIC) 来评估 lisocabtagene maraleucel (liso-cel) 与 axicabtagene ciloleucel (axi-cel) 在复发或难治性大 B 细胞淋巴瘤 (LBCL) 患者。主要数据来源包括来自 TRANSCEND NHL 001 研究的个体患者数据（TRANSCEND [NCT02631044]；N = 256 用于疗效组，N = 269 用于安全组）的 liso-cel 和来自 ZUMA-1 研究 (NCT02348216) 的汇总级数据；对于 axi-cel，N = 101 为功效组，N = 108 为安全组）。研究间在设计、资格标准、基线特征和结果方面的差异进行了评估，并在可行的范围内进行了调整。临床相关的预后因素按等级顺序逐步调整。由于 TRANSCEND 允许使用桥接治疗，但 ZUMA-1 不允许，因此初始疗效和安全性分析包括使用桥接治疗作为匹配因素（移除接受桥接治疗的 TRANSCEND 患者）。随后的敏感性分析排除了这个匹配因素。初步分析显示 TRANSCEND 和 ZUMA-1 在总体和完全缓解率方面的 MAIC 加权疗效结果相似（比值比 [95% 置信区间 (CI)]、1.40 [0.56-3.49] 和 1.21 [0.56-2.64]，分别）和总生存期和无进展生存期（风险比 [95% CI]，分别为 0.81 [0.44–1.49] 和 0.95 [0.58–1.57]）。MAIC 加权的安全结果有利于 liso-cel，全级别和≥ 3 级细胞因子释放综合征（比值比 [95% CI]，分别为 0.03 [0.01-0.07] 和 0.08 [0.01-0.67]）和研究特异性神经系统事件（0.16 [0.08 –0.33] 和 0.05 [0.02–0.15]，分别）。在敏感性分析中，疗效和安全性结果仍然相似，其中不包括使用桥接疗法作为匹配因素。在匹配和调整临床相关预后因素后，与 axi-cel 相比，liso-cel 在三线或后线复发或难治性 LBCL 患者中表现出相当的疗效和更有利的安全性。试用注册：NCT02631044和NCT02348216 分别）。在敏感性分析中，疗效和安全性结果仍然相似，其中不包括使用桥接疗法作为匹配因素。在匹配和调整临床相关预后因素后，与 axi-cel 相比，liso-cel 在三线或后线复发或难治性 LBCL 患者中表现出相当的疗效和更有利的安全性。试用注册：NCT02631044和NCT02348216 分别）。在敏感性分析中，疗效和安全性结果仍然相似，其中不包括使用桥接疗法作为匹配因素。在匹配和调整临床相关预后因素后，与 axi-cel 相比，liso-cel 在三线或后线复发或难治性 LBCL 患者中表现出相当的疗效和更有利的安全性。试用注册：NCT02631044和NCT02348216