Phase Ib study combining ibrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with CD20-positive B-cell non-Hodgkin lymphoma (NHL).

Lymphoma and Plasma Cell Disorders
Session Type and Session Title: 
Oral Abstract Session, Lymphoma
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 8502)
Anas Younes, Ian Flinn, Jesus G. Berdeja, Jonathan W. Friedberg, Sara Alberti, Catherine Thieblemont, Franck Morschhauser, Peter Hellemans, Brett Hall, Johan Smit, Donna Skee, Ronald de Vries, Marija Todorovic, Imran Khan, Nele Fourneau, Yasuhiro Oki; The University of Texas MD Anderson Cancer Center, Houston, TX; Sarah Cannon Research Institute, Nashville, TN; Sarah Cannon Research Institute; Tennessee Oncology, Nashville, TN; University of Rochester, Wilmot Cancer Center, Rochester, NY; Assistance Publique–Hôpitaux de Paris, Hôpital Saint Louis, Paris, France; Centre Hospitalier Régional Universitaire de Lille, Hôpital Claude Huriez, Service Maladies du Sang, Lille, France; Janssen Research & Development, LLC, Beerse, Belgium; Janssen Research & Development, LLC, Spring House, PA; Janssen Research & Development, LLC, Raritan, NJ; Janssen Research & Development, LLC, Belgrade, Serbia

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Abstract Disclosures


Background: Ibrutinib, a first-in-class oral Bruton’s tyrosine kinase inhibitor, has demonstrated single-agent activity in a variety of relapsed or refractory B-cell malignancies with limited toxicity, making it an appropriate drug to combine with standard R-CHOP chemotherapy in patients with previously untreated NHL. Methods: Patients received oral daily dose of ibrutinib (280, 420, or 560 mg) in combination with standard doses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, and vincristine on day 1, and prednisone on days 1 through 5 of each 21-day cycle for up to 6 cycles). The primary objective was to determine the recommended phase 2 dose (RP2D) of ibrutinib in combination with standard R-CHOP (IR-CHOP). The secondary objectives were to assess safety, overall response rate, pharmacokinetics, and pharmacodynamic biomarkers. Results: Seventeen patients (7, 4, and 6 in increasing ibrutinib doses) were enrolled: 59% male, median age 65 (range 46-81) years, diffuse large B-cell lymphoma 47%, mantle cell lymphoma 29% and follicular lymphoma 24%. In the 280 mg cohort, 2 patients had dose-limiting toxicity (DLT): 1 with transient syncope and 1 with periorbital cellulitis; at 560 mg, 1 patient had gastritis (grade 2). The RP2D was established at 560 mg ibrutinib. The most common (≥ 20% of patients) adverse events (AEs) were neutropenia (77%), thrombocytopenia (65%), vomiting (59%), anemia (53%), nausea (47%), fatigue (35%), headache (29%), constipation (24%), diarrhea (24%), and dizziness (24%). To date, 6 patients completed 6 cycles of treatment, and 2 patients discontinued treatment (1 due to noncompliance with the study drug and 1 due to non-DLT AE). At the time of this analysis, of the 10 patients had at least one post baseline tumor, the overall response rate was 100% (7 complete and 3 partial responses). Conclusions: The combination of IR-CHOP has an acceptable safety profile. No new toxicities were noted with adding ibrutinib to R-CHOP. An expansion cohort 560 mg ibrutinib (RP2D) is being opened to further explore the safety and efficacy of IR-CHOP in patients with newly diagnosed diffuse large B-cell lymphomas. Clinical trial information: NCT01569750.