Búa BR, Jiménez-Ubieto A, Sánchez Blanco JJ, et al. - Among patients suffering from non-germinal center B-cell like (non-GCB) diffuse large B-cell lymphoma (DLBCL), this phase II clinical trial was conducted to assess efficacy as well as toxicity of the combination of Ibrutinib with R-GEMOX-D (rituximab, gemcitabine, oxaliplatin and dexamethasone). Participants included patients with histological diagnosis of non-GCB DLBCL (Hans algorithm), with relapsed or refractory disease and non-candidates for autologous stem-cell transplantation. Patients were administered an induction therapy with 6 (in case of complete remission [CR] following cycle 4) or 8 (in case of partial response or stable disease following cycle 4) cycles of R-GEMOX-D at standard doses every 2 weeks, in combination with ibrutinib (560 mg daily), followed by a maintenance therapy with ibrutinib for a maximum of 2 years. Following the 4th cycle, overall response rate and CR rate were estimated to be 53.1% and 34.4%, respectively. These rates were 35.9% and 29.7%, respectively, at the end of induction. The 2-year progression-free survival and overall survival were found to be 20% and 27%, respectively, following a median follow-up of 29 months (0.37-48.9), and were significantly better in cases with non-refractory disease. Findings revealed that high response rates, particularly in non-refractory cases, were conferred by the combination of ibrutinib with R-GEMOX-D as salvage therapy in patients with non-GCB DLBCL. Very early progression occurs in the vast majority of refractory patients, thus this regimen could be considered as a bridge to other consolidation therapies.