A phase I study evaluating ibritumomab tiuxetan (Zevalin (R)) in combination with bortezomib (Velcade (R)) in relapsed/refractory mantle cell and low grade B-cell non-Hodgkin lymphoma

作者：Beaven Anne W^*; Shea Thomas C; Moore Dominic T; Feldman Tatyana; Ivanova Anastasia; Ferraro Madlyn; Ford Peggy; Smith Judith; Goy Andre

来源：Leukemia and Lymphoma, 2012, 53(2): 254-258.

DOI：10.3109/10428194.2011.608445

• Radioimmunotherapy
• proteasome inhibitor
• mantle cell lymphoma
• non-Hodgkin lymphoma
• ibritumomab tiuxetan

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.

• 出版日期2012-2