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

Leuk Lymphoma. 2012 Feb;53(2):254-8. doi: 10.3109/10428194.2011.608445. Epub 2011 Sep 19.

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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols
  • Boronic Acids / therapeutic use*
  • Bortezomib
  • Drug Resistance, Neoplasm*
  • Female
  • Follow-Up Studies
  • Humans
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / mortality
  • Lymphoma, B-Cell / pathology
  • Lymphoma, Mantle-Cell / drug therapy*
  • Lymphoma, Mantle-Cell / mortality
  • Lymphoma, Mantle-Cell / pathology
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Prognosis
  • Pyrazines / therapeutic use*
  • Radioimmunotherapy
  • Salvage Therapy*
  • Survival Rate

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Boronic Acids
  • Pyrazines
  • ibritumomab tiuxetan
  • Bortezomib