Ibrutinib in Combination with R-Gemox-D in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma: Phase II Clinical Trial of the Geltamo Group

AbstractPurpose: This phase II clinical trial evaluated the combination of ibrutinib with rituximab, gemcitabine, and oxaliplatin (R-GemOx) in patients with nongerminal center B-cell–like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Patients and Methods: The IBDCL trial (NCT02692248) included patients with histologic diagnosis of non-GCB DLBCL with relapsed or refractory disease and non-candidates for stem-cell transplantation. Patients received an induction treatment consisting of six or eight cycles of R-GemOx 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. The primary objective was to evaluate the overall response rate after four cycles. Results: Sixty-four patients were included, 72% of them refractory to the last regimen. The overall response rate and complete remission rate after the fourth cycle were 53% [95% confidence interval (CI), 41–65] and 34% (95% CI, 24–46), respectively. Twenty-four (37%) patients started maintenance, and 7 (11%) completed the planned 2 years. After a median follow-up of 29.7 months (range: 0.4–48.6), the estimated 2-year progression-free survival and overall survival were 18% (95% CI, 8–28) and 26% (95% CI, 14–37), respectively. The most common grade ≥3 treatment-related adverse events were thrombocytopenia (44%), neutropenia (30%), and anemia (14%). Grade ≥3 infectious and cardiovascular treatment-related adverse events were reported in 6 (9%) and 1 (2%) patient, respectively. Conclusions: Ibrutinib in combination with R-GemOx, followed by ibrutinib maintenance, demonstrated encouraging antitumor activity with durable responses and a manageable toxicity in patients with non-GCB DLBCL.