CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:An AI model classifies risks of early relapse post-CAR T-cell therapy in a multicenter real-world population with DLBCL.
An AI model classifies risks of early relapse post-CAR T-cell therapy in a multicenter real-world population with DLBCL.
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阿基仑赛(axi-cel)的真实世界(RW)证据不断增加,显示其疗效与关键临床试验相当。然而,57%的患者最终复发,多数需要接受后续治疗。若能识别早期复发风险患者,临床医生即可考虑其他干预,以延长生存。
本研究首先旨在使用自动化计算方法,全面评估axi-cel在加州大学健康系统多中心队列中的真实世界疗效;其次,我们开发了一种决策树机器学习(ML)模型,以识别6个月内早期复发风险患者。研究纳入2017年至2024年间接受axi-cel治疗的416例成人弥漫大B细胞淋巴瘤(DLBCL)患者。中位无进展生存期(PFS)和总生存期(OS)分别为10.1个月和54.4个月;18个月PFS率和OS率分别为41.6%和65.5%。18.8%的患者发生重度CRS,32.5%的患者发生重度ICANS。该ML模型依赖年龄和6项常规实验室检测(乳酸脱氢酶、C反应蛋白、铁蛋白、血细胞比容、血小板计数和凝血酶原时间),受试者工作特征曲线下面积高达0.82。决策曲线分析显示,在较宽的决策阈值范围(0–0.7)内,该模型具有正向净获益,提示其适用于多种临床场景。
本研究进一步确认了axi-cel在不同人群中的真实世界疗效。我们的ML模型提供了一种识别可能从额外干预中获益、从而延长生存患者的新方法。经过前瞻性确证后,该模型和决策树方法有望支持高危DLBCL患者的临床决策。
Accumulating real-world (RW) evidence of axicabtagene ciloleucel (axi-cel) has demonstrated comparable performance to that of pivotal trials.
However, 57% of patients eventually relapse, with most requiring additional therapies. Being able to identify patients with risk of early relapse enables clinicians to consider additional interventions to extend survival outcomes.
This study aimed to first comprehensively evaluate the RW performance of axi-cel in the multicenter University of California Health Systems using automated computational approaches. Second, we developed a decision tree machine learning (ML) model to identify patients with risks of early relapse within 6 months. A total of 416 adult patients with diffuse large B-cell lymphoma (DLBCL) receiving axi-cel between 2017 and 2024 were included in the study. The median progression-free survival (PFS) and overall survival (OS) were 10. 1 and 54.
4 months; the 18-month PFS and OS rates were 41. 6% and 65. 5%, respectively. Severe CRS and ICANS were observed in 18. 8% and 32. 5% of patients. The ML model, relying on age and 6 routinely measured laboratory tests (lactate dehydrogenase, C-reactive protein, ferritin, hematocrit, platelet count, and prothrombin time), achieved a high area under the receiver operating characteristic curve score of 0.
82. The decision curve analysis indicated positive net benefit of the model across a broad range (0-0. 7) of decision thresholds, suggesting clinical utility in diverse scenarios.
This study further confirmed the RW performance of axi-cel in diverse populations.
Our ML model represented a novel approach to identify patients that may benefit from additional interventions to extend survival outcomes. Following prospective confirmation study, our model and decision tree approach may support clinical decision making in patients with high-risk DLBCL.
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