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

Clin Cancer Res. 2024 Sep 3;30(17):3704-3714. doi: 10.1158/1078-0432.CCR-24-0183.

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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adenine* / administration & dosage
  • Adenine* / analogs & derivatives
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Drug Resistance, Neoplasm
  • Female
  • Gemcitabine
  • Humans
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Lymphoma, Large B-Cell, Diffuse* / mortality
  • Lymphoma, Large B-Cell, Diffuse* / pathology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / pathology
  • Oxaliplatin / administration & dosage
  • Oxaliplatin / adverse effects
  • Piperidines* / administration & dosage
  • Pyrimidines / administration & dosage
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use
  • Rituximab / administration & dosage
  • Rituximab / adverse effects
  • Spain / epidemiology
  • Treatment Outcome

Substances

  • ibrutinib
  • Adenine
  • Piperidines
  • Deoxycytidine
  • Gemcitabine
  • Rituximab
  • Oxaliplatin
  • Pyrimidines

Grants and funding