权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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.

项目总结：免疫检查点抑制剂（ICIs）已经显著地改变了黑色素瘤的治疗