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

• Published in: Blood Vol. 131; no. 16; pp. 1805 - 1808
• Main Authors: Sauter, Craig S., Matasar, Matthew J., Schoder, Heiko, Devlin, Sean M., Drullinsky, Pamela, Gerecitano, John, Kumar, Anita, Noy, Ariela, Palomba, Maria L., Portlock, Carol S., Straus, David J., Zelenetz, Andrew D., McCall, Susan J., Miller, Shoshana T., Courtien, Amanda I., Younes, Anas, Moskowitz, Craig H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.04.2018; American Society of Hematology
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Brief Report; Carboplatin - administration & dosage; Carboplatin - adverse effects; Clinical Trials and Observations; Etoposide - administration & dosage; Etoposide - adverse effects; Female; Humans; Ifosfamide - administration & dosage; Ifosfamide - adverse effects; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - metabolism; Lymphoma, Large B-Cell, Diffuse - pathology; Male; Middle Aged; Pyrazoles - administration & dosage; Pyrazoles - adverse effects; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Remission Induction; Rituximab - administration & dosage; Rituximab - adverse effects
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2017-08-802561

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. •Ibrutinib plus R-ICE was safe, tolerable, and was not prohibitive to mobilizing hematopoietic stem cells for autologous transplantation.•A favorable early signal in all evaluable rel/ref non-GC DLBCL achieving a complete metabolic remission was observed.