肿瘤细胞治疗研究
英文原题：Standard-of-care ciltacabtagene autoleucel in earlier versus later lines of therapy for relapsed or refractory multiple myeloma: a nationwide registry analysis.
该分析表明，cilta-cel 用于更早线次治疗可获得深度缓解和较高的 PFS，与 CARTITUDE-4 试验结果一致。
背景：Ciltacabtagene autoleucel（cilta-cel）是一种靶向 BCMA 的嵌合抗原受体（CAR）T 细胞疗法，已获批用于复发或难治性多发性骨髓瘤（RRMM）。在 CARTITUDE-1 研究显示其对多线治疗患者有效后，随机 III 期 CARTITUDE-4 试验证实，对既往接受 1–3 线治疗且来那度胺耐药的患者，cilta-cel 的无进展生存期（PFS）和总生存期均优于标准治疗，促使其于 2024 年扩大适应证。但这一更早治疗线适应证的真实世界结局数据尚缺乏。 方法：研究分析德国干细胞移植与细胞治疗登记系统中，2022 至 2025 年接受标准治疗 cilta-cel 的所有 RRMM 患者。按既往治疗线数分为早期组（1–3 线）和晚期组（>3 线）。主要终点为 PFS；次要终点包括总缓解率、应答转化及安全性结局，包括细胞因子释放综合征、免疫效应细胞相关神经毒性综合征（ICANS）、非 ICANS 神经毒性和非复发死亡率。采用限制性立方样条 Cox 回归和单变量 Cox 模型评估预后相关性。 结果：606 名患者中，177 人（30%）在早期治疗线接受治疗，429 人（70%）在晚期治疗线接受治疗。早期组和晚期组总缓解率分别为 91% 和 88%，完全缓解率分别为 63% 和 54%。cilta-cel 治疗 12 个月 PFS 早期组为 79%，晚期组为 70%。缓解深度是两组 PFS 最强预测因素；无论治疗线数，维持完全缓解的患者 12 个月 PFS 均为 100%。髓外病变对两组均为不良预后因素，而早期组中高危细胞遗传学与 PFS 较差无关。早期组非 ICANS 神经毒性发生率较低（3% 对 8%），非复发死亡率相近（6% 对 7%）。 结论：该分析显示，较早治疗线使用 cilta-cel 可获得深度缓解和较高 PFS，与 CARTITUDE-4 试验一致。这些结果提供了真实世界证据，支持最早在首次复发时使用 cilta-cel，并可作为前瞻性试验以外的参考基准。
BACKGROUND: Ciltacabtagene autoleucel (cilta-cel) is a BCMA-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed or refractory multiple myeloma (RRMM). Following the CARTITUDE-1 results in heavily pretreated patients, the randomized phase 3 CARTITUDE-4 trial demonstrated superior progression-free survival (PFS) and overall survival for cilta-cel compared with standard of care in lenalidomide-refractory patients after one to three prior lines, leading to label expansion in 2024. However, real-world data characterizing outcomes in this earlier-line indication are lacking. METHODS: We analyzed all patients with RRMM receiving standard-of-care cilta-cel between 2022 and 2025 from the German Registry for Stem Cell Transplantation and Cellular Therapy. Patients were stratified by prior lines of therapy into an Early group (1-3 prior lines) and a Late group (> 3 prior lines). The primary endpoint was PFS. Secondary endpoints included overall response rate, response conversion, and safety outcomes including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS), non-ICANS neurotoxicity, and non-relapse mortality. Prognostic associations were assessed using restricted cubic spline Cox regression and univariable Cox models. RESULTS: Of 606 patients, 177 (30%) were treated in the Early and 429 (70%) in the Late setting. The overall response rate was 91% and 88%, with complete response in 63% and 54%, respectively. The 12-month PFS was 79% for Early and 70% for Late cilta-cel. Depth of response was the strongest predictor of PFS in both cohorts, with patients maintaining complete response showing 100% PFS at 12 months irrespective of treatment line. Extramedullary disease was adversely prognostic in both groups, whereas high-risk cytogenetics were not associated with inferior PFS in the Early group. Non-ICANS neurotoxicity occurred less frequently in the Early group (3% versus 8%), while non-relapse mortality was comparable (6% versus 7%). CONCLUSIONS: This analysis demonstrates that cilta-cel in earlier lines of therapy achieves deep responses and high PFS consistent with the CARTITUDE-4 trial. These results provide real-world evidence for the deployment of cilta-cel as early as first relapse and may be a benchmark outside prospective trials.
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