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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：
10282855
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/10282855
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.

项目摘要：免疫检查点抑制剂 (ICIs) 显着改变了黑色素瘤的治疗方法提高总体生存率。在被批准用于黑色素瘤辅助治疗后，它们的使用呈指数级增长正在显着改变癌症生存的面貌。尽管有生存益处，但 ICI 的使用可能受到限制通过各种器官的脱靶炎症反应和自身免疫。急性免疫性疾病的临床表型试验中已清楚地记录了毒性。然而，它们潜在的长期不利影响及其影响质量生活（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治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 ICI 引起的不良事件和持续炎症会增加症状接受治疗的一部分黑色素瘤患者的负担并对功能和生活质量产生负面影响，并且升高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 240 名黑色素瘤患者（从辅助 ICI 开始时起）的前瞻性队列中检验这一假设通过2年的随访进行治疗。我们将确定 irAE 的发生率、临床表型、发生时间和严重程度，并将通过两年的随访纵向评估患者报告的结果。我们将使用经过验证的仪器和生态瞬时评估技术，通过患者实时评估不良事件和症状负担发起的报告。最后，我们将描述患者免疫特征（免疫细胞表型和炎症细胞因子）从基线到 2 年的随访，并评估它们与 irAE 和症状负担的关联。职业发展计划：此申请的主要目标是支持 Abdelwahab 博士的职业生涯发展成为一名独立的免疫流行病学家，重点关注癌症或癌症背景下产生的自身免疫它的疗法。 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) 科学写作和口头演示。 Abdelwahab 博士整理了一份由黑色素瘤医学肿瘤学教授兼 Solid 主任 Cassian Yee 博士领导的杰出导师团队癌症免疫学研究中心的肿瘤细胞疗法和症状教授 Annemieke Kavelaars 博士作为联合主要导师在 MD 安德森癌症中心 (MDACC) 进行研究。这辅以指导咨询委员会成员包括具有肿瘤专业知识的黑色素瘤肿瘤内科副教授 Adi Diab 博士免疫学和免疫治疗，Suarez-Almazor 博士，风湿病学和临床免疫学教授，Susan 博士彼得森，行为科学教授兼评估、干预和测量设施主任，博士。 Sanjay Shete，行为和社会统计主管。 MDACC 是领先的癌症研究、护理、和预防，为 Abdelwahab 博士提供了极好的培训环境。