title: A phase 1/1b study of rituximab, bendamustine, and ibrutinib in patients with untreated and relapsed/refractory non-Hodgkin lymphoma.
abstract: Ibrutinib has single agent activity of 22% to 68% in relapsed B-cell non-Hodgkin lymphoma(NHL). This study evaluated the safety and efficacy of ibrutinib combined with rituximab (R) and bendamustine. Patients received R (375 mg/m(2)) on day 1, bendamustine (90 mg/m(2)) on days 1 and 2, and ibrutinib (280 or 560 mg) on days 1 to 28 every 28 days for 6 cycles followed by ibrutinib alone until progression. Forty-eight patients enrolled, including 12 patients with follicular lymphoma (FL), 16 with diffuse large B-cell lymphoma (DLCL), and 17 with mantle cell lymphoma (MCL). No dose-limiting toxicities were observed. Patients received a median of 8 cycles, with 26 completing 6 cycles and continuing ibrutinib alone in cycles 7 to 34. The overall response (OR) rate was 72%, with 52% complete responses (CRs). By histology, the OR rate was 94% (76% CR) in MCL, 37% (31% CR) in DLCL, and 90% (50% CR) in FL. Grade 3 to 4 toxicities included lymphopenia (77%), neutropenia (33%), thrombocytopenia (19%), and rash (25%). Median progression-free survival has not been reached (95% CI, 8.7 months to not reached). The recommended phase 2 dose of ibrutinib in combination with R-bendamustine in patients with NHL is 560 mg. The combination has promising efficacy, particularly in MCL and FL. This trial was registered at www.clinicaltrials.gov as #NCT01479842.
authors.affiliation: Division of Hematology, Department of Internal Medicine.
authors.forename: Kami
authors.initials: K
authors.lastname: Maddocks
authors.affiliation: Division of Hematology, Department of Internal Medicine.
authors.forename: Beth
authors.initials: B
authors.lastname: Christian
authors.affiliation: Division of Hematology, Department of Internal Medicine.
authors.forename: Samantha
authors.initials: S
authors.lastname: Jaglowski
authors.affiliation: Division of Hematology, Department of Internal Medicine.
authors.forename: Joseph
authors.initials: J
authors.lastname: Flynn
authors.affiliation: Division of Hematology, Department of Internal Medicine.
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Jones
authors.affiliation: Division of Hematology, Department of Internal Medicine.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Porcu
authors.affiliation: Center for Biostatistics.
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.affiliation: Clinical Trials Office, Arthur G. James Comprehensive Cancer Center and Research Institute, and.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Jenkins
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, OH.
authors.forename: Gerard
authors.initials: G
authors.lastname: Lozanski
authors.affiliation: Division of Hematology, Department of Internal Medicine.
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.affiliation: Division of Hematology, Department of Internal Medicine.
authors.forename: Kristie A
authors.initials: KA
authors.lastname: Blum
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage / Q000009:adverse effects; D010880:Piperidines; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D000069283:Rituximab; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D009588:Nitrogen Mustard Compounds; D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D000069283:Rituximab; D000069461:Bendamustine Hydrochloride; D000225:Adenine