A phase 1 study of ibrutinib in combination with R-ICE in patients with relapsed or primary refractory DLBCL Academic Article uri icon


MeSH Major

  • Bone Marrow Neoplasms
  • Burkitt Lymphoma
  • Central Nervous System Neoplasms
  • DNA-Binding Proteins
  • Gene Rearrangement
  • Genes, bcl-2
  • Genes, myc
  • Germinal Center
  • Lymphoma, Large B-Cell, Diffuse


  • In the postrituximab era, approximately half of the patients with relapsed or refractory (rel/ref) diffuse large B-cell lymphoma (DLBCL) fail to achieve a chemosensitive response to standard salvage therapy, and are thus ineligible to proceed to autologous stem cell transplantation with curative intent. The Bruton tyrosine kinase inhibitor ibrutinib demonstrates single-agent activity in rel/ref DLBCL, particularly of non-germinal center (non-GC) cell of origin. We conducted a single-center phase 1 study evaluating dose-escalated ibrutinib, in a 3-by-3 design, in combination with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in physiologically transplant-eligible rel/ref DLBCL patients. Twenty-one patients have been treated and are evaluable for toxicity with no dose-limiting toxicities observed through expansion with ibrutinib at 840 mg daily at dose level 3. Of the 20 patients evaluable for response, per modern International Conference on Malignant Lymphoma criteria, 11 patients achieved complete remission (CR) and 7 patients achieved partial remission for an overall response rate of 90%. All evaluable patients with non-GC DLBCL achieved a metabolic CR. Ibrutinib in combination with R-ICE demonstrates tolerability and efficacy in rel/ref DLBCL, particularly of non-GC phenotype. This treatment program warrants further investigation in later-phase studies. This trial was registered at www.clinicaltrials.gov as #NCT02219737.

publication date

  • April 19, 2018



  • Academic Article



  • eng

PubMed Central ID

  • PMC5909762

Digital Object Identifier (DOI)

  • 10.1182/blood-2017-08-802561

PubMed ID

  • 29386196

Additional Document Info

start page

  • 1805

end page

  • 1808


  • 131


  • 16