Faculty Collaboration Database

A phase 1/1b study of rituximab, bendamustine, and ibrutinib in patients with untreated and relapsed/refractory non-Hodgkin lymphoma. Blood 2015 Jan 08;125(2):242-8

Date

10/31/2014

Pubmed ID

25355819

DOI

10.1182/blood-2014-08-597914

Scopus ID

2-s2.0-84920951834 (requires institutional sign-in at Scopus site)   116 Citations

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.

Author List

Maddocks K, Christian B, Jaglowski S, Flynn J, Jones JA, Porcu P, Wei L, Jenkins C, Lozanski G, Byrd JC, Blum KA

Author

Samantha M. Jaglowski MD, MPH Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenine
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Murine-Derived
Antineoplastic Combined Chemotherapy Protocols
Bendamustine Hydrochloride
Female
Humans
Kaplan-Meier Estimate
Lymphoma, Non-Hodgkin
Male
Maximum Tolerated Dose
Middle Aged
Neoplasm Recurrence, Local
Nitrogen Mustard Compounds
Piperidines
Pyrazoles
Pyrimidines
Rituximab
Young Adult