Neurocognitive and Patient-Reported Outcomes after Chimeric Antigen Receptor T-Cell Therapy: A Controlled Comparison

嵌合抗原受体 T 细胞治疗后的神经认知和患者报告结果：对照比较

基本信息

批准号：
10444276
负责人：
HEATHER S.L. JIM
金额：
$ 70.73万
依托单位：
H. LEE MOFFITT CANCER CTR & RES INST
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10444276
关键词：
Acute Address Admission activity Adult Adverse event Age Attention B-Cell Lymphomas Behavior Behavioral Biological Blood CAR T cell therapy Cancer Survivor Cell Aging Cellular Phone Cognition Cognitive Collaborations Data Delirium Deterioration Disease Disease-Free Survival Ecological momentary assessment Education Encephalopathies Energy Metabolism Event Exhibits FDA approved Family Fatigue Fever Frequencies Future Goals Hypotension Hypoxia Impaired cognition In complete remission Individual Inflammation Internet Intervention Length of Stay Life Long Term Survivorship Malignant Neoplasms Measures Memory Mental Depression Neurocognition Neurocognitive Neurologic Neuropsychological Tests Neuropsychology Outcome Pain Participant Patient Outcomes Assessments Patient Self-Report Patients Performance Performance Status Phase I/II Trial Physical activity Population Prior Chemotherapy Quality of life Questionnaires Refractory Relapse Research Risk Factors Self Assessment Sleep Societies Stress Supportive care Symptoms Technology Time Woman actigraphy base chimeric antigen receptor clinical risk cognitive performance cognitive task comorbidity contextual factors cytokine release syndrome improved innovation insight leukemia/lymphoma malignant breast neoplasm modifiable risk neurotoxic neurotoxicity novel objective response rate processing speed protective factors recruit response sedentary lifestyle sex side effect survivorship

项目摘要

PROJECT SUMMARY There is widespread excitement about chimeric antigen receptor (CAR) T-cell therapy, which causes complete disease response in 40%-54% of adults with relapsed/refractory large B-cell lymphoma (LBCL), compared to a response rate of 7% to chemotherapy prior to the advent of CAR T-cell therapy. For the first time, long-term disease-free survival is possible for patients with advanced LBCL. CAR T-cell therapy causes a unique profile of adverse events, including cytokine release syndrome (CRS) and neurologic events, which may be risk factors for cancer-associated cognitive decline (CACD). However, little is known about neurocognition and patient- reported outcomes (PROs; e.g., symptoms, quality of life or QOL) in CAR T-cell therapy patients. The goal of the current study is to investigate longitudinal changes in PROs and CACD, outcomes that are highly relevant to survivorship, in the first year after CAR T-cell therapy. We will recruit 204 LBCL patients treated with CAR T-cell therapy and 102 age-, sex-, and education-matched individuals without cancer. Participants will be assessed at pre-CAR T-cell therapy baseline and 3 and 12 months later to capture acute and longer-term outcomes. At each time point, participants will complete internet-based neuropsychological testing, validated PRO questionnaires, and 7-day smartphone-based ecological momentary assessment (EMA) of cognition and self-reported risk factors for CACD (i.e., fatigue, depression, pain, stress). Actigraphy during EMA periods will be used to objectively measure sleep, physical activity, and sedentary behavior as behavioral factors for QOL and CACD. Blood will be collected and banked at each assessment for future examination of biological mechanisms (e.g., inflammation, accelerated cellular aging). Data will be used to address the following aims: 1) to examine baseline differences and longitudinal changes in patient-reported outcomes and cognition in CAR T-cell therapy recipients and controls, 2) to identify demographic, contextual, and clinical risk factors that are associated with worse cognition in CAR T-cell therapy recipients compared to controls, and 3) to determine behavioral protective factors associated with better cognition among CAR T-cell therapy recipients and controls. This research will be highly impactful, providing the data needed to educate patients and their families about CAR T-cell therapy in collaboration with the Leukemia and Lymphoma Society. Analyses focused on risk and protective factors will provide insights into potential targets of intervention to improve QOL and CACD in this novel cancer survivor population.

项目概要嵌合抗原受体 (CAR) T 细胞疗法引起广泛关注，该疗法可导致完全与患有复发/难治性大 B 细胞淋巴瘤 (LBCL) 的成人相比，40%-54% 的疾病有反应在 CAR T 细胞疗法出现之前，化疗的反应率为 7%。第一次，长期晚期 LBCL 患者有可能实现无病生存。 CAR T 细胞疗法具有独特的特征不良事件，包括细胞因子释放综合征 (CRS) 和神经系统事件，这些可能是危险因素用于癌症相关认知能力下降（CACD）。然而，人们对神经认知和患者知之甚少。 CAR T 细胞治疗患者的报告结果（PRO；例如症状、生活质量或 QOL）。目标是当前的研究是调查 PRO 和 CACD 的纵向变化，这些结果与 CAR T 细胞治疗后第一年的存活率。我们将招募204名接受CAR T细胞治疗的LBCL患者治疗和 102 名年龄、性别和教育程度匹配的未患癌症的个体。参与者将在以下时间接受评估 CAR T 细胞治疗前基线以及 3 个月和 12 个月后，以捕获急性和长期结果。在每个时间点，参与者将完成基于互联网的神经心理学测试、经过验证的 PRO 问卷、以及为期 7 天的基于智能手机的认知和自我报告风险生态瞬时评估 (EMA) CACD 的因素（即疲劳、抑郁、疼痛、压力）。 EMA 期间的体动记录仪将用于客观地衡量睡眠、体力活动和久坐行为作为 QOL 和 CACD 的行为因素。每次评估时都会收集并储存血液，以供将来检查生物机制（例如，炎症、加速细胞老化）。数据将用于实现以下目标：1）检查基线 CAR T 细胞治疗接受者患者报告的结果和认知的差异和纵向变化和控制，2) 识别与病情恶化相关的人口统计学、背景和临床风险因素与对照组相比，CAR T 细胞治疗接受者的认知能力，以及 3) 确定行为保护因素与 CAR T 细胞治疗接受者和对照者更好的认知相关。这项研究将高度具有影响力，提供所需数据来教育患者及其家人了解 CAR T 细胞疗法与白血病和淋巴瘤协会合作。重点分析风险和保护因素深入了解潜在的干预目标，以改善这位新型癌症幸存者的生活质量和 CACD 人口。