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

项目总结 嵌合抗原受体(CAR)T细胞疗法正在改变成人血液病患者的护理 其他情况下预后不佳的恶性肿瘤。多达40%的大B细胞淋巴瘤(LBCL)患者 在注射CAR T细胞疗法后，预计至少可以存活两年，而平均总存活率 在CAR T细胞疗法问世前的6个月。此外，更多的试验正在进行中，以评估汽车 T细胞治疗其他血液病和实体恶性肿瘤。因此，有越来越多的人口 经历与CAR T细胞治疗相关的独特副作用的幸存者，如细胞因子释放 综合征(CRS)和神经毒性。有关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(AEs)。相比之下，患者报告的结果(PRO)提供了 从患者的角度来看的重要信息，这些信息是对AEs的补充。FDA将专业人士定义为： 1)疾病症状，2)治疗副作用，3)生活质量。尽管有经过充分验证的 衡量疾病症状(#1)和生活质量(#3)，目前还没有有效的衡量标准来捕捉 CAR T细胞疗法的独特副作用(#2)。缺乏这样的措施限制了开展研究和 对患者进行有关这种新疗法的教育。这项研究将开发并验证一种评估患者的新方法-- 报道了CAR T细胞疗法的副作用。措施开发将遵循FDA的措施开发 指南，并提供英文和西班牙文版本。在目标1中，将对20名学生进行定性访谈 CAR T细胞接受者，20名非正式家庭照顾者，以及20名具有CAR T细胞专业知识的医疗提供者 心理治疗。患者和照顾者将在生存轨迹上进行抽样，以确保足够的 代表了自CAR T细胞治疗以来的各种经验。定性访谈将确定患者的身份- 报告的副作用是常见的、严重的、令人痛苦的和在护理过程中具有诊断重要性的 T细胞治疗、康复和生存。副作用将被映射到功能评估 慢性病治疗(FAIT)项目库700个独特的专业项目。将为副作用编写新的项目 没有对应的Facit项的。在目标2中，将对另外20名患者进行认知访谈 进行以确保题库的可读性、可理解性和表面有效性，以及生成 根据需要添加其他项目。在目标3中，收敛、发散、区分效度和可靠性将 在一项横断面研究中评估了150名CAR T细胞治疗患者自治疗以来的不同时间。 目前的项目具有很强的创新性。从研究角度来看，这项措施将在以下方面提供重要数据 接受CAR T细胞治疗的观察性、干预性和治疗性试验。从一家诊所 从角度来看，这项措施将导致更好地检测患者报告的副作用，以提高支持性 关爱这群人。

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.