Metformin prolonged the survival of diffuse large B-cell lymphoma and grade 3b follicular lymphoma patients responding to first-line treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone: a prospective phase II clinical trial

Abstract

Background: With the addition of rituximab to chemotherapy, the response rates of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma grade 3b (FL3b) have been significantly improved. However, recurrence remains to be the hinder of long survival of the patients. Metformin is a widely used anti-diabetic agent and has an anti-lymphoma effect through adenosine monophosphate (AMP)-activated protein kinase activation in vitro and in vivo. Methods: We conducted a single center, prospective, single-arm phase II clinical trial of metformin for maintenance therapy in patients with DLBCL or FL3b who achieved complete remission after the first-line treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), and analyzed the efficacies of metformin maintenance. Results: The patients received metformin maintenance had significantly better overall survival (OS) than those without metformin maintenance, especially for the diabetic patients. Patients with age >60, elevated serum lactate dehydrogenase (LDH), or International Prognostic Index (IPI) score ≥2 were benefit from metformin maintenance, as well as those with tumor cell expressing Ki67 ≥80%, or with non-germinal center B-cell-like (non-GCB) subtype. In multivariate analysis, age >60, elevated serum LDH and diabetic patients without metformin maintenance were the three independent unfavorable prognostic factors for OS. Conclusions: Metformin could thus be a safe and economic maintenance agent for elderly and high-risk patients not suitable for transplantation.