Ibrutinib in Combination with R-GemOx in Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma of Nongerminal Center B-cell–like Type: Phase II Clinical Trial of the Spanish GELTAMO Group
Beatriz Rey-Búa, Carlos Grande, José Javier Sánchez Blanco, Pau Abrisqueta, Antonio Gutiérrez, Ángel Ramírez Páyer, Eva Giné, Izaskun Zeberio, María José Terol, Fátima de la Cruz Vicente, Rafael Andreu, M.J. Ramírez, Adolfo de la Fuente, María C. Viguria, María Jesús Peñarrubia, Ana Jiménez Ubieto, Santiago Montes‐Moreno, Armando López‐Guillermo, M. D. Caballero, Alejandro Martı́n
Abstract
PURPOSE: 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.