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

Craig S. Sauter, Matthew J. Matasar, Heiko Schoder, Sean M. Devlin, Pamela Drullinsky, John Gerecitano, Anita Kumar, Ariela Noy, Maria L. Palomba, Carol S. Portlock, David J. Straus, Andrew D. Zelenetz, Susan J. McCall, Shoshana T. Miller, Amanda I. Courtien, Anas Younes, Craig Moskowitz

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1805-1808
Number of pages4
JournalBlood
Volume131
Issue number16
DOIs
StatePublished - Apr 19 2018
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Sauter, C. S., Matasar, M. J., Schoder, H., Devlin, S. M., Drullinsky, P., Gerecitano, J., Kumar, A., Noy, A., Palomba, M. L., Portlock, C. S., Straus, D. J., Zelenetz, A. D., McCall, S. J., Miller, S. T., Courtien, A. I., Younes, A., & Moskowitz, C. (2018). A phase 1 study of ibrutinib in combination with R-ICE in patients with relapsed or primary refractory DLBCL. Blood, 131(16), 1805-1808. https://doi.org/10.1182/blood-2017-08-802561