title: A phase I study evaluating ibritumomab tiuxetan (Zevalin®) in combination with bortezomib (Velcade®) in relapsed/refractory mantle cell and low grade B-cell non-Hodgkin lymphoma.
abstract: Proteasome inhibitors may inhibit DNA repair of radiation-induced strand breaks and adducts thereby making the combination of radioimmunotherapy and bortezomib a promising approach. Preclinical models demonstrate additive/synergistic effects from combining DNA damaging agents with proteasome inhibitors. This phase I trial combines ibritumomab tiuxetan with bortezomib. Twelve patients with relapsed/refractory mantle cell and low grade B-cell non-Hodgkin lymphoma were enrolled. Patients with prior radioimmunotherapy were prohibited. The maximum tolerated dose (MTD) was not reached. No dose limiting toxicities (DLTs) occurred in cohort 1 or 2. One of six patients on cohort 3 had DLTs of asthenia, dizziness and neuropathy. Grade 3/4 thrombocytopenia occurred in two patients (16%) and grade 3/4 neutropenia in three patients (25%). Five subjects (41.7%) had complete responses (CRs) and one patient had a partial response (8.3%) for an overall response rate (ORR) of 50%. The combination of standard dose ibritumomab tiuxetan and bortezomib at 1.5 mg/m(2) is well tolerated with a promising response rate.
authors.affiliation: Duke University Medical Center, Durham, NC 27710, USA. Anne.beaven@duke.edu
authors.forename: Anne W
authors.initials: AW
authors.lastname: Beaven
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Shea
authors.forename: Dominic T
authors.initials: DT
authors.lastname: Moore
authors.forename: Tatyana
authors.initials: T
authors.lastname: Feldman
authors.forename: Anastasia
authors.initials: A
authors.lastname: Ivanova
authors.forename: Madlyn
authors.initials: M
authors.lastname: Ferraro
authors.forename: Peggy
authors.initials: P
authors.lastname: Ford
authors.forename: Judith
authors.initials: J
authors.lastname: Smith
authors.forename: Andre
authors.initials: A
authors.lastname: Goy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011719:Pyrazines / Q000627:therapeutic use*; D016499:Radioimmunotherapy; D016879:Salvage Therapy; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; C422802:ibritumomab tiuxetan; D000069286:Bortezomib