肿瘤细胞治疗研究
英文原题：Real-world patient-reported symptomatic adverse events and concordance with physician assessments after CAR T-cell therapy in patients with aggressive B-cell lymphomas: a prospective study.
在 2022 年 6 月 29 日至 2024 年 2 月 26 日期间，共 170 例患者被纳入该研究。
**背景：**嵌合抗原受体（CAR）T 细胞在治疗血液系统恶性肿瘤方面展现出显著潜力。本研究旨在调查接受 CAR-T 治疗的侵袭性 B 细胞淋巴瘤患者短期内自行报告的症状性不良事件，并与治疗医生报告的事件进行比较，同时考察可预测总体短期治疗负担的因素。**方法：**这是一项前瞻性、多中心观察研究，在意大利 13 个中心招募患者。符合条件者为年满 18 岁、确诊侵袭性 B 细胞淋巴瘤且计划接受 axicabtagene ciloleucel（axi-cel）、tisagenlecleucel（tisa-cel）或 brexucabtagene autoleucel（brexu-cel）治疗的患者。本分析的主要目标是评估总体及按性别、年龄分层的短期患者报告症状性不良事件发生率。输注后第 10 天采用不良事件通用术语标准患者报告结果版（PRO-CTCAE）评估，该量表根据临床相关性选择 19 个项目，包括吞咽困难、食欲下降、恶心、腹泻、水肿、脱发、头晕、注意力困难、记忆困难、一般疼痛、头痛、肌痛、关节痛、失眠、疲劳、焦虑、沮丧、悲伤和寒战。研究还按 CAR-T 产品类型评估症状性不良事件发生率，并由治疗血液科医生使用 CTCAE 进行相应评估以作比较；医生报告的事件与患者报告的对应事件进行匹配。此外，研究计算总体症状负担评分，并在多变量分析中将其作为结局指标，考察人口社会学及临床资料、输注前 EORTC QLQ-C30 患者报告身体功能等预测因素。本研究已在 ClinicalTrials.gov 注册（NCT06026644），目前已停止入组且完成随访。**结果：**2022 年 6 月 29 日至 2024 年 2 月 26 日，共纳入 170 例患者。中位年龄为 61.1 岁（四分位距 [IQR] 51.1–68.5），中位随访时间为 23.7 个月（17.7–24.6）；女性 53 例（31%），男性 117 例（69%）。多数患者确诊为弥漫大 B 细胞淋巴瘤（118 例，69%），其次为套细胞淋巴瘤（32 例，19%）和原发性纵隔大 B 细胞淋巴瘤（20 例，12%）。接受 axi-cel、tisa-cel 和 brexu-cel 输注的患者分别为 98 例（58%）、39 例（23%）和 32 例（19%）。165 例到达第 10 天评估时点，其中 143 例（87%）完成相应 PRO-CTCAE 项目。19 项症状性不良事件中有 12 项的任何级别发生率超过 50%：疲劳 123/141（87%）、食欲下降 116/139（83%）、失眠 112/142（79%）、寒战 103/142（73%）、腹泻 99/141（70%）、悲伤 81/141（57%）、一般疼痛 78/143（55%）、头晕 78/143（55%）、关节痛 74/142（52%）、肌痛 73/143（51%）、头痛 73/143（51%）及注意力受损 72/142（51%）。中重度症状中，超过 30% 患者报告疲劳（78/141，55%）、食欲下降（74/139，53%）、腹泻（63/141，45%）、寒战（49/142，35%）和失眠（44/142，31%）。医生经常低估患者症状。例如，胃肠道症状报告持续偏少。
BACKGROUND: Chimeric antigen receptor (CAR) T cells have shown considerable promise in treating patients with haematological malignancies. We aimed to investigate short-term patient-reported symptomatic adverse events in patients with aggressive B-cell lymphomas treated with CAR T-cell therapy and compare them with those reported by their treating physicians. We also examined factors predicting overall short-term burden of therapy. METHODS: This was a prospective, observational, multicentre study enrolling patients across 13 centres in Italy. Eligible patients were aged 18 years and older with a confirmed diagnosis of aggressive B-cell lymphoma. All patients were scheduled to undergo CAR T-cell therapy with one of the following products: axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), or brexucabtagene autoleucel (brexu-cel). The primary objective of this analysis was to assess the prevalence of short-term patient-reported symptomatic adverse events overall and by sex and age categories. The primary objective was evaluated on day 10 after infusion via the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), which includes 19 items selected based on their clinical relevance, including: difficulty swallowing, decreased appetite, nausea, diarrhoea, swelling, hair loss, dizziness, concentration difficulty, memory difficulty, general pain, headache, muscle pain, joint pain, insomnia, fatigue, anxiety, discouragement, sadness, and chills. Prevalence of symptomatic adverse events was also assessed by type of CAR T-cell product. Additionally, the study was designed to allow a corresponding adverse event assessment via the CTCAE by treating haematologists for comparative analysis. Adverse events reported by physicians were matched with corresponding adverse events reported by patients. Furthermore, an overall symptom burden score was computed and used as outcome variable in multivariable analysis to examine factors predicting short-term burden of therapy, including sociodemographic and clinical data and pre-infusion patient-reported physical functioning by the EORTC QLQ-C30. The study is registered with ClinicalTrials.gov, NCT06026644, and is closed to accrual and follow-up is complete. FINDINGS: Between June 29, 2022, and Feb 26, 2024, 170 patients were included in the study. The median age of patients was 61 1 years (IQR 51 1-68 5) and the median follow-up was 23 7 months (17 7-24 6). 53 (31%) of 170 enrolled patients were female and 117 (69%) were male. Most patients were diagnosed with diffuse large B-cell lymphoma (118 [69%] patients), followed by mantle cell lymphoma (32 [19%] patients) and primary mediastinal large B-cell lymphoma (20 [12%] patients). 98 (58%) patients were infused with axi-cel, 39 (23%) with tisa-cel, and 32 (19%) with brexu-cel. 165 patients reached the day 10 timepoint, of whom 143 (87%) completed the corresponding PRO-CTCAE item list. We observed a prevalence (any grade) of more than 50% across 12 of the 19 symptomatic adverse events examined: fatigue (123 [87%] of 141 patients), decreased appetite (116 [83%] of 139 patients), insomnia (112 [79%] of 142 patients), chills (103 [73%] of 142 patients), diarrhoea (99 [70%] of 141 patients), sadness (81 [57%] of 141 patients), general pain (78 [55%] of 143 patients), dizziness (78 [55%] of 143 patients), joint pain (74 [52%] of 142 patients), muscle pain (73 [51%] of 143 patients), headache (73 [51%] of 143 patients), and impaired concentration (72 [51%] of 142 patients). Inspection of moderate to severe grades revealed that more than 30% of patients reported fatigue (78 [55%] of 141 patients), decreased appetite (74 [53%] of 139 patients), diarrhoea (63 [45%] of 141 patients), chills (49 [35%] of 142 patients), and insomnia (44 [31%] of 142 patients). Physicians frequently under-reported symptoms in their patients. For example, gastrointestinal symptoms were consistently under-reported, including di
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