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Immune-Related Adverse Events in Melanoma Patients Receiving Adjuvant Immune Checkpoint Inhibitor Therapy

接受辅助免疫检查点抑制剂治疗的黑色素瘤患者的免疫相关不良事件

基本信息

批准号：
10471406
负责人：
Noha Abdelwahab Hassan Ali Hassan
金额：
$ 11.39万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-18 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10471406
关键词：
Acute Adjuvant Adjuvant Therapy Adverse effects Adverse event Advisory Committees Area Autoimmune Autoimmune Diseases Autoimmunity Behavioral Behavioral Sciences Benefits and Risks Biological Markers Biological Response Modifiers Biometry Cancer Center Cancer Patient Cancer Survivor Cancer Survivorship Caring Cell Therapy Cells Chronic Clinical Clinical Immunology Clinical Management Clinical Research Clinical Trials Clinical assessments Committee Members Complement Data Data Collection Development Development Plans Disease Ecological momentary assessment Effectiveness Environment Epidemiologist Epidemiology Fatigue Foundations Future Genes Genetic Genetic Markers Genetic Risk Goals Immune Immune checkpoint inhibitor Immune system Immunobiology Immunologic Adjuvants Immunologics Immunology Incidence Inflammation Inflammatory Inflammatory Response Interleukin-6 Intervention Link Malignant Neoplasms Measurement Measures Medical Oncology Mental Depression Mentors Mentorship Methods Oral Organ Outcome Measure Outcomes and Health Services Research Pathogenesis Pathway interactions Patient Outcomes Assessments Patients Phenotype Physician Executives Play Population Prevention Prospective Studies Prospective cohort Prospective cohort study Quality of life Recommendation Reporting Research Resected Rheumatology Risk Role Secondary to Severities Single Nucleotide Polymorphism Sleep disturbances Solid Solid Neoplasm Specific qualifier value Symptoms T-Lymphocyte Technology Assessment Testing Therapeutic Therapy trial Time Toxic effect Training Translational Research Writing acute toxicity adverse event risk anticancer research associated symptom body system career development checkpoint therapy clinical care clinical phenotype clinical practice cytokine experience follow-up high risk immune activation immune-related adverse events innovation instrument melanoma mid-career faculty mobile computing neoplasm immunotherapy practice setting professor prospective social statistics surgical risk tumor immunology

项目摘要

PROJECT SUMMARY: Immune checkpoint inhibitors (ICIs) have transformed the treatment of melanoma, significantly enhancing overall survival. The exponential increase in their use after being approved for melanoma in the adjuvant setting is significantly changing the lanscape of cancer survivorship. Inspite of the survival benefits, the use of ICI can be limited by off-target inflammatory responses and autoimmunity in various organs. The clinical phenotypes of the acute immune toxicities have been clearly documented in trials. Yet, their potential long-term adverse effects, and their impact quality of life (QOL) are still undetermined. The overall goal of the proposed study is to understand the full impact of adjuvant ICI therapy, including its potential toxicity/symptom burden and its immune correlates in melanoma patients receiving regular clinical care. We hypothesize that: adverse events and sustained inflammation induced by adjuvant ICIs increase symptom burden and negatively impact function and QOL in a subset of melanoma patients receiving therapy, and that elevated expression of pro-inflammatory cytokines and T-cell signatures during therapy correlate with the toxicity and symptom burden. We will test this hypothesis in a prospective cohort of 240 melanoma patients from the initiation of adjuvant ICI therapy through 2 years of follow-up. We will determine the incidence, clinical phenotypes, timing, and severity of irAEs, and will longitudinally assess patients reported outcomes through 2 years of follow-up. We will use validated instruments and ecological momentary assessments technology to assess adverse events and symptom burden in real time via patient- initiated reports. Lastly, we will characterize patient immune signatures (immune cell phenotypes and inflammatory cytokines) from baseline through 2 years of follow-up and evaluate their association with irAEs and symptom burden. CAREER DEVELOPMENT PLAN: The primary objective of this application is to support Dr. Abdelwahab’s career development into an independent immuno-epidemiologist with a focus on autoimmunity arising in the context of cancer or its therapy. Dr. Abdelwahab proposed training in four areas 1) immunology, 2) epidemiology and biostatistics, 3) health services and outcomes research, and 4) scientific writing and oral presentations. Dr. Abdelwahab has assembled an outstanding mentorship team led by Dr. Cassian Yee, Professor in Melanoma Medical Oncology and Director of Solid Tumor Cell Therapy in the Center for Cancer Immunology Research, and Dr. Annemieke Kavelaars, Professor in Symptom Research at MD Anderson Cancer Center (MDACC) as co-primary mentors. This is complemented by mentoring advisory committee members including Dr. Adi Diab, Associate Professor in Melanoma Medical Oncology with expertise in tumor immunology and immunotherapy, Dr. Suarez-Almazor, Professor of Rheumatology and Clinical Immunology, Dr. Susan Peterson, Professor in Behavioral Science and Director of the Assessment, Intervention and Measurement Facility, and Dr. Sanjay Shete, Chief of Behavioral and Social Statistics. MDACC, a leading center in cutting edge of cancer research, care, and prevention, is an excellent training environment for Dr. Abdelwahab.

项目总结：免疫检查点抑制剂（ICI）显著改变了黑色素瘤的治疗，提高整体生存率。在被批准用于黑色素瘤的辅助治疗后，正在显着改变癌症生存的格局。尽管有生存益处，但ICI的使用可能受到限制通过各种器官中的脱靶炎症反应和自身免疫。急性免疫性肺结核的临床表型在试验中已经清楚地记录了毒性。然而，其潜在的长期不利影响，以及其影响质量，生活质量（QOL）仍不确定。拟议研究的总体目标是了解辅助ICI的全面影响治疗，包括其潜在的毒性/症状负担及其在接受常规化疗的黑色素瘤患者中的免疫相关性。临床护理我们假设：辅助性ICI诱导的不良事件和持续炎症增加了症状在接受治疗的黑色素瘤患者亚组中，治疗期间促炎细胞因子和T细胞特征的表达与毒性和症状相关负担我们将在一个由240名黑色素瘤患者组成的前瞻性队列中从开始辅助ICI开始测试这一假设通过2年的随访治疗。我们将确定irAE的发生率、临床表型、时间和严重程度，并将通过2年随访纵向评估患者报告的结局。我们将使用经过验证的仪器和生态瞬时评估技术，通过患者- 发起的报告。最后，我们将描述患者的免疫特征（免疫细胞表型和炎症反应）。细胞因子），并评估其与irAE和症状负荷的相关性。职业发展计划：本申请的主要目的是支持阿卜杜勒瓦哈卜博士的职业生涯发展成为一个独立的免疫流行病学家，专注于癌症背景下产生的自身免疫，它的治疗。Abdelwahab博士建议在四个领域进行培训：1）免疫学，2）流行病学和生物统计学，3）健康服务和成果研究，以及4）科学写作和口头报告。Abdelwahab博士召集了一个杰出的导师团队由Cassian Yee博士领导，他是黑色素瘤医学肿瘤学教授和Solid 癌症免疫学研究中心的肿瘤细胞治疗和症状学教授Annemieke Kavelaars博士在MD安德森癌症中心（MDACC）作为共同主要导师进行研究。这是由辅导咨询补充委员会成员包括Adi Diab博士，黑色素瘤医学肿瘤学副教授，具有肿瘤方面的专业知识免疫学和免疫疗法，Suarez-Almazor博士，流变学和临床免疫学教授，Susan博士彼得森，行为科学教授和评估，干预和测量设施主任，博士。 Sanjay Shete，行为和社会统计局局长。MDACC是癌症研究、护理、和预防，是一个很好的培训环境阿卜杜勒瓦哈卜博士。