Combining Approved Drugs for Alcoholism and Cancer to Treat Diffuse Large B-cell Lymphoma
Principal Investigator: Dr. Jason Romancik
Disease: Diffuse Large B-cell Lymphoma
Research Description: Diffuse large B-cell lymphoma (DLBCL) and other aggressive subtypes of B-cell non-Hodgkin lymphoma (NHL) affect men and women of all ages and causes approximately 10,000 deaths per year in the US. Initial treatment with multiagent chemotherapy cures some patients, but up to 40% will relapse. Autologous stem cell transplant and chimeric antigen receptor (CAR) T-cell therapy have curative potential for a subset of patients with relapsed disease, but those who fail these therapies have a very poor prognosis. Using a computational approach, the research team has discovered that disulfiram, used to treat chronic alcoholism, can inhibit a biomarker found to be a driver of aggressive non-Hodgkin lymphomas such as DLBCL. Furthermore, in laboratory studies and animal models, the team has shown that disulfiram can make human lymphoma cells more sensitive to immune-based killing. This open-label, pilot study will test the safety and efficacy of combining disulfiram with pembrolizumab, a drug used to treat a variety of cancers, in patients with relapsed DLBCL. If the combination of disulfiram and pembrolizumab is safe and demonstrates early evidence of efficacy, this could potentially lead to the repurposing of disulfiram as an anti-cancer agent for DLBCL and possibility other forms of cancer.
Funding Partners: Goldman Philanthropic Partnerships and others
CWR funding role: Primary funder