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


Authors: 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. H.
Article Title: A phase 1 study of ibrutinib in combination with R-ICE in patients with relapsed or primary refractory DLBCL
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. © 2018 by The American Society of Hematology.
Keywords: adult; cancer survival; clinical article; event free survival; treatment response; aged; primary tumor; overall survival; cancer combination chemotherapy; drug safety; unspecified side effect; cancer patient; rituximab; carboplatin; progression free survival; infection; multiple cycle treatment; anemia; etoposide; ifosfamide; febrile neutropenia; clostridium difficile infection; bloodstream infection; staphylococcus infection; catheter infection; heart atrium arrhythmia; parainfluenza virus infection; sinus tachycardia; diffuse large b cell lymphoma; ibrutinib; human; priority journal; article
Journal Title: Blood
Volume: 131
Issue: 16
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2018-04-19
Start Page: 1805
End Page: 1808
Language: English
DOI: 10.1182/blood-2017-08-802561
PROVIDER: scopus
PMCID: PMC5909762
PUBMED: 29386196
DOI/URL:
Notes: Article -- Export Date: 2 July 2018 -- Source: Scopus
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MSK Authors
  1. Carol Portlock
    174 Portlock
  2. Craig Moskowitz
    366 Moskowitz
  3. Ariela Noy
    202 Noy
  4. Maria Lia Palomba
    118 Palomba
  5. Heiko Schoder
    275 Schoder
  6. Craig Steven Sauter
    150 Sauter
  7. Andrew D Zelenetz
    538 Zelenetz
  8. Matthew J Matasar
    116 Matasar
  9. David J Straus
    203 Straus
  10. Susan J McCall
    13 McCall
  11. Anita Kumar
    50 Kumar
  12. Sean McCarthy Devlin
    277 Devlin
  13. Anas Younes
    186 Younes
  14. Shoshana T Miller
    4 Miller