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

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。

项目成果

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Noha Abdelwahab Hassan Ali Hassan其他文献

Noha Abdelwahab Hassan Ali Hassan的其他文献

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{{ truncateString('Noha Abdelwahab Hassan Ali Hassan', 18)}}的其他基金

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
  • 批准号:
    10664973
  • 财政年份:
    2021
  • 资助金额:
    $ 11.39万
  • 项目类别:
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
  • 批准号:
    10471406
  • 财政年份:
    2021
  • 资助金额:
    $ 11.39万
  • 项目类别:

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