Metformin combined with chemotherapy improved the treatment response of patients with high-grade B-cell lymphoma and diffuse large B-cell lymphoma

Abstract

Abstract High-grade B-cell lymphomas (HGBCL) with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH) are aggressive and often resistant to standard chemotherapy, and metformin has shown promising anti-lymphoma effects. This study evaluated how lactate dehydrogenase (LDH), albumin (ALB), and oncogene expression levels affect outcomes in HGBCL and diffuse large B-cell lymphoma (DLBCL), and assessed the impact of adding metformin to chemotherapy. This prospective study, conducted between 2021 and 2024, involved HGBCL and DLBCL patients, of which 162 patients with DLBCL and 120 with DTH-HGBL were analyzed, focusing on their diabetes status and metformin use. Patients received 8 cycles of either CHOP or R-CHOP chemotherapy, and metformin use was monitored. Treatment response was evaluated after completion, with a median follow-up of 3 years. Serum levels of LDH and albumin were measured. Additionally, tissue samples were prepared and stained to detect bcl-2, c-myc, and bcl-6 proteins using immunohistochemistry. Among 282 lymphoma patients, 60–68% achieved complete remission, with better survival linked to 60.63% lower LDH, 68.08% higher ALB, and negative oncogene markers. Diabetic patients on metformin showed the best overall survival (OS), while those not on metformin had the worst ( p  = 0.05). Metformin maintenance in diabetic lymphoma patients was linked to lower LDH (79.07%), higher ALB (86.04%), fewer relapses, and better survival (51.16%), in DTH-HGBCL patients, compared to those not on metformin. In 259 lymphoma patients, high c-myc and bcl-2/bcl-6 expression was linked to poorer treatment response and survival ( p  < 0.001). Adding metformin to chemotherapy improved remission rates and 3-year survival, especially in patients with these protein expressions ( p  < 0.001), suggesting metformin helps overcome chemotherapy resistance in high-risk cases. The study found that metformin improves remission and survival rates in high-risk lymphoma patients, and in diabetic DLBCL and DTH-HGBCL patients. It suggests metformin may be a helpful addition to standard lymphoma treatments.