Safety, efficacy, and cost-effectiveness of rituximab for multicentric Castleman disease in Malawi

项目摘要/摘要 Matthew Painschab博士正在申请Fogarty国际中心K01国际研究科学家 发展奖。Painschab博士作为一名年轻的全球卫生研究员表现出了希望，但需要 进一步培训，以实现研究的独立性。这一奖项将为他提供五年的指导 他将花费75%的研究时间在北卡罗来纳大学马拉维项目和Kamuzu Central 马拉维首都利隆圭的一家医院。他的目标是成为一名专家和独立研究员 撒哈拉以南非洲(SSA)癌症治疗的临床试验和成本效益，特别是多中心 卡斯特尔曼病和其他卡波西肉瘤相关疱疹病毒(KSHV)相关疾病。他的初选 该奖项的导师是Satih Gopal博士，医学博士，公共卫生硕士(LMIC的主要导师，癌症临床研究 SSA)和Stephanie Wheeler博士，博士，公共卫生硕士(主要美国导师，决策建模和成本- 有效性分析)。通过导师指导、课程学习和实践经验的结合，Dr。 Painschab建议完成以下培训目标：1)临床试验高级培训 设计和实施；2)微观成本计算和成本效益建模方面的高级培训；3) KSHV病理生物学方面的高级培训。这项培训计划将支持MCD的严格研究计划，一种生活- 以全身炎症和淋巴结病为特征的威胁性淋巴增生性疾病 与KSHV和人类免疫缺陷病毒(HIV)密切相关。这种病要流行得多 在SSA，因为KSHV和艾滋病毒感染的流行率要高得多。化疗很少，如果有的话， 有效地预防这种疾病的发病率和死亡率。然而，在高收入的小规模研究中 在一些国家，抗CD20的单抗利妥昔单抗一直是B细胞上常见的一种蛋白质 在诱导长期缓解方面有效。在本应用程序中，我们建议测试 在马拉维进行的一项基于利妥昔单抗治疗MCD(AIM 1)的II期研究。我们还将进行一次 马拉维MCD治疗的综合微成本研究，并使用AIM 1的结果来建立 马尔可夫模型(AIM 2)，我们将使用该模型来分析基于利妥昔单抗的治疗的成本-效果。这 研究将建立一个独特的MCD患者和样本的预期队列，可以用于 未来的独立研究奖，以更好地了解这种新出现的艾滋病毒相关共病和 改善SSA和高收入国家的患者结局。

PROJECT SUMMARY/ABSTRACT Dr. Matthew Painschab is applying for a Fogarty International Center K01 International Research Scientist Development Award. Dr. Painschab has shown promise as a young investigator in global health but needs further training to achieve research independence. This award will provide him with five years of mentored research time and he will spend >75% of the award period based at UNC Project Malawi and Kamuzu Central Hospital in Lilongwe, the capital city of Malawi. His goal is to become an expert and independent researcher in clinical trials and cost-effectiveness of cancer care in sub-Saharan Africa (SSA), specifically, multicentric Castleman’s disease and other Kaposi sarcoma-associated herpesvirus (KSHV)-related diseases. His primary mentors for this award are Dr. Satish Gopal, MD, MPH (Primary LMIC-based Mentor, cancer clinical research in SSA) and Dr. Stephanie Wheeler, PhD, MPH (Primary US-based Mentor, decision modeling and cost- effectiveness analysis). Through a combination of mentorship, coursework, and practical experience, Dr. Painschab proposes to accomplish the following training objectives: 1) advanced training in clinical trials design and implementation; 2) advanced training in microcosting and cost-effectiveness modeling; and 3) advanced training in KSHV pathobiology. This training plan will support a rigorous research plan in MCD, a life- threatening lymphoproliferative disorder characterized by systemic inflammation and lymphadenopathy that is strongly associated with KSHV and human immunodeficiency virus (HIV). This disease is much more prevalent in SSA because of a much higher prevalence of KSHV and HIV infections. Chemotherapy is rarely, if ever, effective in preventing morbidity and mortality from this disease. However, in small studies in high income countries, rituximab, a monoclonal antibody against CD20, a protein commonly found on B cells, has been effective in inducing long-term remissions. In this application, we propose testing the safety and efficacy of rituximab-based treatment for MCD (AIM 1) in a single arm, phase II study in Malawi. We will also conduct a comprehensive microcosting study of treatment of MCD in Malawi and use outcomes from AIM 1 to establish a Markov model (AIM 2) that we will use to analyze the cost-effectiveness of rituximab-based therapy. This research will establish a unique prospective cohort of MCD patients and samples that can be leveraged for future independent research awards to better understand this emerging HIV-associated comorbidity and improve patient outcomes in both SSA and high-income countries.