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

• 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
• 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

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.

项目摘要 嵌合抗原受体（CAR）T细胞疗法引起了广泛的兴奋， 复发性/难治性大B细胞淋巴瘤（LBCL）成人患者中40%-54%的疾病缓解率， 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患者的无病生存是可能的。CAR T细胞疗法导致独特的特征 不良事件，包括细胞因子释放综合征（CRS）和神经系统事件，可能是风险因素 癌症相关认知能力下降（CACD）然而，我们对神经认知和患者认知知之甚少。 报告的结果（PRO;例如，症状，生活质量或QOL）。的目标 目前的研究是调查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、性别和教育相匹配的无癌症个体。参加者将在 CAR前T细胞治疗基线以及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，验证PRO问卷， 和7天基于智能手机的认知和自我报告风险的生态瞬时评估（EMA） CACD的因素（即，疲劳、抑郁、疼痛、压力）。EMA期间的活动记录将用于 客观地测量睡眠、体力活动和久坐行为作为QOL和CACD的行为因素。 在每次评估时将采集血液并储存，用于将来的生物学机制检查（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细胞治疗接受者中患者报告的结局和认知的差异和纵向变化 2）确定与更糟的疾病相关的人口统计学，背景和临床风险因素， 与对照相比，CAR T细胞治疗接受者的认知，以及3）确定行为保护因素 与CAR T细胞治疗接受者和对照组之间更好的认知相关。这项研究将是高度 有影响力，提供所需的数据，教育患者及其家属关于CAR T细胞治疗， 与白血病和淋巴瘤协会合作。对风险和保护因素的分析将 提供对潜在干预靶点的深入了解，以改善这种新型癌症幸存者的QOL和CACD 人口