Citations

PURPOSE In patients with diffuse large B-cell lymphoma (DLBCL), most relapses occur within the first 2 years of diagnosis. We sought to define the rate and outcome of late relapses that occurred after achieving event-free survival at 24 months (EFS24). METHODS We prospectively followed 1,324 patients with newly diagnosed DLBCL from 2002 to 2015 and treated with immunochemotherapy. Cumulative incidences of late DLBCL and indolent lymphoma relapses were analyzed as competing events. Postrelapse survival was defined as time from first relapse to death from any cause. RESULTS In 847 patients who achieved EFS24, the cumulative incidence of late relapse was 6.9% at 3 years, 9.3% at 5 years, and 10.3% at 8 years after EFS24. The incidence of DLBCL relapse was similar in patients with DLBCL alone at diagnosis (6.3% at 5 years), compared with patients with concurrent indolent lymphoma at diagnosis (5.2%; P = .46). However, the rate of indolent lymphoma relapse was higher in patients with concurrent indolent lymphoma (7.4% v 2.1% at 5 years; P < .01). In patients with DLBCL alone, the rate of DLBCL relapse was similar in the germinal center B-cell–like (GCB) (4.1% at 5 years) and non-GCB (4.0%; P = .71) subtypes, whereas the rate of indolent lymphoma relapse was higher in patients with the GCB subtype (3.9% v 0.0% at 5 years; P = .02). Postrelapse survival was inferior for patients who relapsed with DLBCL than for those who relapsed with indolent lymphoma (median 29.9 months v unreached; P < .01). CONCLUSION Patients with DLBCL with a concurrent indolent lymphoma and those with the GCB subtype had a higher rate of late relapse, owing to increased relapses with indolent lymphoma. Patients who relapsed with DLBCL had a worse prognosis than those who relapsed with indolent lymphoma.

SummaryThe diabetes mellitus (DM) drug metformin targets mechanistic/mammalian target of rapamycin and inhibits lymphoma growth in vitro. We investigated whether metformin affected outcomes of newly diagnosed diffuse large B‐cell (DLBCL, n = 869) and follicular lymphoma (FL, n = 895) patients enrolled in the Mayo component of the Molecular Epidemiology Resource cohort study between 2002 and 2015. Hazard ratios (HR) and 95% confidence intervals (CIs) adjusted for age, sex, body mass index, prognostic index and treatment were used to estimate the association of metformin exposure (No DM/No metformin; DM/No metformin; DM/Metformin) with event‐free (EFS), lymphoma‐specific (LSS) and overall (OS) survival. Compared to No DM/No metformin DLBCL patients, there was no association of DM/Metformin (n = 48; HR = 1·05, 95% CI 0·59–1·89) or DM/No metformin(n = 54; HR = 1·41, 95% CI 0·88–2·26) with EFS; results were similar for LSS and OS. Compared to No DM/No metformin FL patients, there was no association of DM/Metformin (n = 37; HR = 1·16, 95% CI 0·71–1·89) or DM/No metformin (n = 19; HR = 1·16, 95% CI 0·66–2·04) with EFS; results were similar for LSS. However, DM/Metformin was associated with inferior OS (HR = 2·17; 95% CI 1·19–3·95) compared to No DM/No metformin. In conclusion, we found no evidence that metformin use was associated with improved outcomes in newly diagnosed DLBCL and FL.