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：
10664973
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/10664973
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 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 Health Services Research Immune Immune checkpoint inhibitor Immune system Immunobiology Immunologic Adjuvants Immunologics Immunology Incidence Inflammation Inflammatory Inflammatory Response Interleukin-6 Intervention Learning Link Malignant Neoplasms Measurement Measures Medical Oncology Mental Depression Mentors Mentorship Methods Oral Organ Outcome Measure Outcomes 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 System T-Lymphocyte Technology Assessment Testing Therapeutic Therapy trial Time Toxic effect Training Translational Research Writing acute toxicity adverse event risk anticancer research associated symptom biomarker identification 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)显著改变了黑色素瘤的治疗提高总体存活率。在佐剂环境中被批准用于黑色素瘤后，它们的使用量呈指数级增长正在显著改变癌症存活期的面貌。尽管ICI对生存有好处，但其使用可能是有限的通过各种器官的非靶标炎症反应和自身免疫。急性免疫性疾病的临床表型毒性已经在试验中得到了明确的记录。然而，它们潜在的长期不利影响，以及它们对生命(QOL)仍未确定。拟议研究的总体目标是了解佐剂ICI的全部影响。接受常规治疗的黑色素瘤患者的治疗，包括其潜在的毒性/症状负担及其免疫相关性临床护理。我们假设：由佐剂ICIS引起的不良事件和持续性炎症增加了症状接受治疗的一部分黑色素瘤患者的负担和负面影响功能和生活质量，并提高促炎症细胞因子和T细胞信号在治疗期间的表达与毒性和症状相关负担。我们将在240名接受ICI辅助治疗的黑色素瘤患者的前瞻性队列中测试这一假说。通过2年随访进行治疗。我们将确定irAEs的发生率、临床表型、时间和严重程度，并将通过2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已启动报告。最后，我们将描述患者的免疫特征(免疫细胞表型和炎症细胞因子)，并评估其与irAEs和症状负担的关系。职业发展计划：本申请的主要目标是支持Abdelwahab博士的职业生涯发展成为独立的免疫流行病学家，专注于癌症或癌症背景下产生的自身免疫它的治疗方法。Abdelwahab博士提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)科学写作和口头陈述。Abdelwahab博士已经组装了一个由黑色素瘤内科肿瘤学教授兼Solid主任Cassian Yee博士领导的杰出导师团队癌症免疫研究中心的肿瘤细胞疗法，以及症状教授Annemieke Kavelaars博士作为共同的主要导师在MD安德森癌症中心(MDACC)进行研究。辅以辅导建议作为补充委员会成员包括具有肿瘤专业知识的黑色素瘤内科肿瘤学副教授Adi Diab博士免疫学和免疫疗法，风湿学和临床免疫学教授Suarez-Almazor博士行为科学教授兼评估、干预和测量设施主任彼得森博士说。行为和社会统计负责人Sanjay Shete说。MDACC是领先的癌症研究、护理、对于Abdelwahab博士来说，这是一个极好的培训环境。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Pathologic Predictors of Response to Treatment of Immune Checkpoint Inhibitor-Induced Kidney Injury.

DOI：
10.3390/cancers14215267
发表时间：
2022-10-27
期刊：
Cancers
影响因子：
5.2
作者：
通讯作者：

Utilization of Immunotherapy for the Treatment of Hepatocellular Carcinoma in the Peri-Transplant Setting: Transplant Oncology View.

DOI：
10.3390/cancers14071760
发表时间：
2022-03-30
期刊：
Cancers
影响因子：
5.2
作者：
Abdelrahim M;Esmail A;Saharia A;Abudayyeh A;Abdel-Wahab N;Diab A;Murakami N;Kaseb AO;Chang JC;Gaber AO;Ghobrial RM
通讯作者：
Ghobrial RM