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

Abstract

<h3>Context</h3> 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). <h3>Objective</h3> The main objective was to evaluate the overall response rate (ORR) after four cycles. <h3>Patients</h3> Histological diagnosis of non-GCB DLBCL (Hans algorithm) with relapsed or refractory disease and non-candidates for autologous stem cell transplantation. <h3>Design</h3> 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. <h3>Results</h3> 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 (<PR) to the last regimen. ORR and CR rate after cycle 4 were 53.1% and 34.4%, respectively. Patients with non-refractory disease had significantly higher ORR (56% <i>vs</i> 44%, p=0.003) and CR rate (82% <i>vs</i> 18%, p<0.01) than patients with refractory disease. After a median follow-up of 29 months (0.37–48.9), the estimated 2-year PFS and OS were 20% and 27%, respectively. PFS was better in patients with non-refractory disease (29%) <i>vs</i> refractory (13%) (p<0.01); OS were 43% <i>vs</i> 17% (p=0.013). In the multivariate analysis, status of lymphoma at study entry significantly influenced PFS (HR 3.03; 95% CI 1.6–5.7; p<0.01) and OS (HR 2.2; 95% CI 1.2–4.2; p=0.016) independently from the IPI and the number of previous treatment lines. The most frequent grade 3–5 adverse events (AE) (>10% of patients) were thrombocytopenia (51.6%), neutropenia (46.9%), anemia (21.9%), and diarrhea (15.6%). <h3>Conclusions</h3> 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. <h3>Funding</h3> Janssen (NCT02692248)