ABCL-181: Updated Results of a Phase 2 Study from GELTAMO Investigating the Combination of Ibrutinib with R-GEMOX in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Context In the present phase II clinical trial (NCT02692248), we investigated the efficacy and toxicity of the combination of ibrutinib with R-GEMOX-D in patients with non-germinal center B-cell like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Objective The main objective was to evaluate the overall response rate (ORR) after four cycles. Patients Histological diagnosis of non-GCB DLBCL (Hans algorithm) with relapsed or refractory disease and non-candidates for autologous stem cell transplantation. Design Induction treatment with six (in cases of complete remission [CR] after cycle 4) or eight (in cases of partial response [PR] or stable disease after cycle 4) cycles of R-GEMOX-D at standard doses every 2 weeks, in combination with ibrutinib (560 mg daily), followed by a maintenance treatment with ibrutinib for a maximum of 2 years. Results Sixty-four patients (median age 67 [25–84] years) were included. Patients had received a median of two previous lines of treatment; 61% were refractory ( 10% of patients) were thrombocytopenia (51.6%), neutropenia (46.9%), anemia (21.9%), and diarrhea (15.6%). Conclusions The combination of ibrutinib with R-GEMOX-D is associated with high response rates, especially in non-refractory patients. The vast majority of refractory patients progress very early, so this regimen could be considered as a bridge to other consolidation therapies. Biological studies analyzing cell of origin by gene expression profiling, minimal residual disease, and mutational spectrum are in progress. Funding Janssen (NCT02692248)