Development and Validation of a Patient-Reported Measure Assessing Chimeric Antigen Receptor (CAR) T-Cell Therapy-Related Side Effects

项目摘要 嵌合抗原受体（CAR）T细胞疗法正在改变血液病成人患者的护理 恶性肿瘤患者，否则他们的健康状况很差。高达40%的大B细胞淋巴瘤（LBCL）患者 与平均总生存期相比，在输注CAR T细胞治疗后， 在CAR-T细胞疗法出现之前的6个月。此外，还有更多的试验正在进行中，以评估CAR 其他血液和实体恶性肿瘤的T细胞治疗。因此，越来越多的人 经历与CAR T细胞治疗相关的独特副作用（如细胞因子释放）的幸存者 综合征（CRS）和神经毒性。关于CAR T细胞疗法毒性的数据几乎完全来自 临床试验中医生评定的不良事件（AE）。相比之下，患者报告结局（PRO）提供了 从患者的角度来看，补充AE的重要信息。FDA将PRO定义为： 1)疾病的症状，2）治疗的副作用，和3）生活质量。虽然有一些经过充分验证的 疾病症状（#1）和生活质量（#3）的措施，没有经过验证的措施，捕捉 CAR T细胞疗法的独特副作用（#2）。缺乏这种措施限制了进行研究的努力， 对病人进行这种新疗法的教育。这项研究将开发和验证一种评估患者的新方法- 报告了CAR T细胞疗法的副作用。措施制定将遵循FDA措施制定 指南，并以英文和西班牙文提供。在目标1中，将对20名 CAR T细胞接受者，20名非正式家庭护理人员和20名具有CAR T细胞专业知识的医疗提供者 疗法将在生存轨迹中对患者和护理人员进行采样，以确保充分 代表了自CAR T细胞治疗以来的各种经历。定性访谈将确定患者- 在CAR治疗过程中报告的常见、严重、痛苦和诊断重要的副作用 T细胞治疗，恢复和生存。副作用将被映射到功能评估中， 慢性疾病治疗（FACIT）项目库的700个独特的PRO项目。新的项目将被写入副作用 没有相应的FACIT项目。在目标2中，将对另外20名患者进行认知访谈， 为了保证试题库的可读性、可理解性和表面效度， 根据需要增加项目。在目标3中，聚合效度、发散效度和区分效度以及信度将被 在一项横断面研究中评估了自治疗以来不同时间的150名CAR T细胞治疗患者。 目前的项目具有很强的创新性。从研究的角度来看，这项措施将提供重要的数据， 在CAR T细胞治疗接受者中进行的观察性、干预性和治疗性试验。从临床 从长远来看，该措施将导致更好地检测患者报告的副作用，以提高支持性 照顾这个人口。

PROJECT SUMMARY Chimeric antigen receptor (CAR) T-cell therapy is transforming care for adult patients with hematological malignancies who have otherwise poor prognoses. Up to 40% of patients with large B cell lymphoma (LBCL) can expect to survive at least two years after infusion of CAR T-cell therapy, in contrast to a mean overall survival of 6 months before the advent of CAR T-cell therapy. Moreover, many more trials are underway to evaluate CAR T-cell therapy for other hematologic and solid malignancies. As a result, there is an increasing population of survivors who experience the unique side effects associated with CAR T-cell therapy such as cytokine release syndrome (CRS) and neurotoxicity. Data on toxicities of CAR T-cell therapy come almost exclusively from physician-rated adverse events (AEs) on clinical trials. In contrast, patient-reported outcomes (PROs) provide important information from the patient’s perspective that is complementary to AEs. The FDA defines PROs as: 1) symptoms of disease, 2) side effects of treatment, and 3) quality of life. Although there are well-validated measures of symptoms of disease (#1) and quality of life (#3), there are no validated measures that capture the unique side effects of CAR T-cell therapy (#2). Lack of such a measure limits attempts to conduct research and patient education about this novel therapy. This study will develop and validate a new measure assessing patient- reported side effects of CAR T-cell therapy. Measure development will follow FDA measure development guidelines and be available in English and Spanish. In Aim 1, qualitative interviews will be conducted with 20 CAR T-cell recipients, 20 informal family caregivers, and 20 medical providers with expertise in CAR T-cell therapy. Patients and caregivers will be sampled across the survivorship trajectory to ensure adequate representation of a variety of experiences since CAR T-cell therapy. Qualitative interviews will identify patient- reported side effects that are common, severe, distressing, and diagnostically important over the course of CAR T-cell therapy, recovery and survivorship. Side effects will be mapped on to the Functional Assessment of Chronic Illness Therapy (FACIT) item library of 700 unique PRO items. New items will be written for side effects that do not have a corresponding FACIT item. In Aim 2, cognitive interviews with 20 additional patients will be conducted to ensure the readability, comprehensibility, and face validity of the item bank as well as generate additional items as needed. In Aim 3, convergent, divergent, and discriminant validity as well as reliability will be evaluated in a cross-sectional study assessing 150 CAR T-cell therapy patients at various times since treatment. The current project is highly innovative. From a research perspective, the measure will provide important data in observational, interventional, and therapeutic trials with CAR T-cell therapy recipients. From a clinical perspective, the measure will lead to a better detection of patient-reported side effects to improve supportive care for this population.