肿瘤细胞治疗研究
英文原题：Development and Validation of a Prediction Model of Outcome After B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Multiple Myeloma.
Development and Validation of a Prediction Model of Outcome After B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Multiple Myeloma.
RRMM 患者接受 CAR-T 后的结局在欧洲和美国之间具有可比性。MyCARe 模型可能有助于在患者特定亚组中优化 CAR-T 细胞的时机。
尽管CAR-T 疗法（CAR-T）细胞是复发/难治性多发性骨髓瘤（RRMM）的成熟疗法，但目前尚无预测结局的成熟模型来识别可能从 CAR-T 中获益最大的患者。
这是一项国际回顾性观察性研究，纳入接受当前可获得的商业化或学术机构生产的抗B细胞成熟抗原（BCMA）CAR-T输注的RRMM患者。我们描述了欧洲（n = 136）和美国（n = 133）的特征和结局。在训练队列（欧洲）中，复发/进展的独立预测因素构建了一个简单的预测模型（骨髓瘤CAR-T复发 [MyCARe] 模型），该模型经外部验证（美国队列），并在患者特异性和治疗特异性亚组中进行了测试。
总体缓解率为87%，且在两个队列间相当，完全缓解见于48%（欧洲）和49%（美国）。中位复发时间为5个月，输注后<5个月早期复发在各队列中均显示生存较差，12个月总生存率分别为30%（欧洲）和14%（美国）。存在髓外疾病或浆细胞白血病、来那度胺难治、高危细胞遗传学以及淋巴细胞清除时铁蛋白升高，是早期复发或进展的独立预测因素。每个因素计1分，形成三层MyCARe模型：评分0-1（低危）、评分2-3（中危）、评分4（高危）。MyCARe模型与不同的5个月复发/进展发生率显著相关（P < .001）：低危组7%、中危组27%、高危组53%。该模型在美国队列中得到验证，并在各亚组中保持对缓解、生存和结局的预后价值。
PURPOSE: Although chimeric antigen receptor T therapy (CAR-T) cells are an established therapy for relapsed/refractory multiple myeloma (RRMM), there are no established models predicting outcome to identify patients who may benefit the most from CAR-T. PATIENTS AND METHODS: This is an international retrospective observational study including patients with RRMM infused with currently available commercial or academically produced anti-B-cell maturation antigen (BCMA) CAR-T. We describe characteristics and outcomes in Europe (n = 136) and the United States (n = 133). Independent predictors of relapse/progression built a simple prediction model (Myeloma CAR-T Relapse [MyCARe] model) in the training cohort (Europe), which was externally validated (US cohort) and tested within patient- and treatment-specific subgroups. RESULTS: The overall response rate was 87% and comparable between both cohorts, and complete responses were seen in 48% (Europe) and 49% (the United States). The median time to relapse was 5 months, and early relapse <5 months from infusion showed poor survival across cohorts, with the 12-month overall survival of 30% (Europe) and 14% (the United States). The presence of extramedullary disease or plasma cell leukemia, lenalidomide-refractoriness, high-risk cytogenetics, and increased ferritin at the time of lymphodepletion were independent predictors of early relapse or progression. Each factor received one point, forming the three-tiered MyCARe model: scores 0-1 (low risk), scores 2-3 (intermediate risk), and a score of 4 (high risk). The MyCARe model was significantly associated with distinct 5-month incidence of relapse/progression ( P < .001): 7% for low-risk, 27% for intermediate-risk, and 53% for high-risk groups. The model was validated in the US cohort and maintained prognostic utility for response, survival, and outcomes across subgroups. CONCLUSION: Outcomes of patients with RRMM after CAR-T are comparable between Europe and the United States. The MyCARe model may facilitate optimal timing of CAR-T cells in patient-specific subgroups.
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