While CD19-directed CAR T-cell therapy represents a transformative immunotherapy for relapsed/refractory large B-cell lymphoma (r/r LBCL), more than 50% of patients ultimately progress or relapse. Recently, the International Metabolic Prognostic Index (IMPI) – incorporating age, stage, and metabolic tumor volume (MTV) – was shown to improve prognostication for LBCL frontline treatment. Here, we examine its utility to predict toxicity and survival in CAR-T recipients. This multicenter observational study spanning six international sites included 504 patients with available 18FDG-PET/CT imaging at last response assessment prior to lymphodepletion. Optimal CAR-adapted MTV thresholds were identified in a development cohort (n = 256) and incorporated into a CAR-T-specific IMPI (“CAR-IMPI”). The prognostic performance of CAR-IMPI was validated in an independent cohort (n = 248). CAR-IMPI risk categories, defined by the median (1.35) and terciles (1.07, 1.58), demonstrated significant discrimination for progression-free survival (PFS; p < 0.0001) and overall survival (OS; p < 0.0001) in both cohorts. Multivariate Cox regression confirmed CAR-IMPI as an independent predictor of survival, accounting for pre-lymphodepletion LDH and CRP, performance status, treatment center, and CAR-T product. Patients in the CAR-IMPI high-risk category experienced increased severity of CRS and ICANS, and higher rates of intensive care unit (ICU) admissions. In an exploratory analysis, combining CAR-IMPI with established indices of high-risk systemic inflammation (CAR-HEMATOTOX, InflaMix) further enhanced survival stratification. The CAR-IMPI may provide a potent and validated PET-based tool for risk stratification of clinical outcomes in patients with r/r LBCL receiving CD19 CAR-T therapy. Our data highlight the utility of combining clinical and radiological modalities, with implications for patient selection and the anticipated level-of-care for toxicity management.
尽管CD19靶向CAR-T细胞疗法是治疗复发/难治性大B细胞淋巴瘤（r/r LBCL）的一种变革性免疫疗法，但超过50%的患者最终会出现病情进展或复发。近期研究显示，结合年龄、分期和代谢肿瘤体积（MTV）的国际代谢预后指数（IMPI）可优化LBCL一线治疗的预后评估。本研究旨在探讨该指数在预测CAR-T治疗患者毒性和生存方面的应用价值。这项多中心观察性研究涵盖六个国际中心，共纳入504例在淋巴清除前末次疗效评估中拥有可用¹⁸FDG-PET/CT影像数据的患者。我们首先在开发队列（n=256）中确定了适配CAR-T治疗的最佳MTV阈值，并据此构建了CAR-T特异性IMPI指数（"CAR-IMPI"）。随后在独立验证队列（n=248）中评估了CAR-IMPI的预后效能。根据中位数（1.35）和三分位数（1.07，1.58）定义的CAR-IMPI风险分级在两个队列中均对无进展生存期（PFS；p<0.0001）和总生存期（OS；p<0.0001）展现出显著区分能力。多变量Cox回归分析证实，在纳入淋巴清除前乳酸脱氢酶、C反应蛋白、体能状态、治疗中心和CAR-T产品类型等因素后，CAR-IMPI仍是生存期的独立预测因子。CAR-IMPI高危组患者出现更严重的细胞因子释放综合征和免疫效应细胞相关神经毒性综合征，且入住重症监护室的比率更高。探索性分析显示，将CAR-IMPI与现有高风险系统性炎症指数（CAR-HEMATOTOX，InflaMix）联用可进一步提升生存分层效能。CAR-IMPI可能为接受CD19 CAR-T治疗的r/r LBCL患者提供一种有效且经过验证的PET影像学风险分层工具。我们的研究数据凸显了临床与影像学指标结合的应用价值，对患者筛选和毒性管理的预期护理层级具有重要指导意义。
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