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

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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.