90Y-ibritumomab tiuxetan, fludarabine, busulfan and antithymocyte globulin reduced-intensity allogeneic transplant conditioning for patients with advanced and high-risk B-cell lymphomas

Ann Oncol. 2015 Jan;26(1):193-198. doi: 10.1093/annonc/mdu503. Epub 2014 Oct 30.

Abstract

Background: Patients with advanced B-cell non-Hodgkin's lymphoma (NHL) refractory to initial chemotherapy or relapsing after autologous stem-cell transplantation have a poor prognosis. Allogeneic stem-cell transplantation after reduced-intensity conditioning (RIC) regimen can be a therapeutic option. However, the high incidence of relapse remains a challenging issue. We speculated that the incorporation of (90)Y-Ibritumomab tiuxetan into a fludarabine-based RIC regimen would improve the lymphoma control without overwhelming toxicity. Our aim was to evaluate the safety of (90)Y-Ibritumomab tiuxetan in association with such a regimen in a prospective multicenter phase II trial.

Patients and methods: Thirty-one patients with advanced lymphoma from five distinct institutions were included between February 2008 and October 2010. Thirty patients in complete or partial response after failure of a median of 3 (range, 2-4) previous chemotherapy regimens including autologous transplant in 29 were evaluable for nonrelapse mortality (NRM) at day 100 post-transplant that was the primary end point.

Results: With a median follow-up of 32 months (range, 29-60 months), the 2-year event-free and overall survivals of the whole study group were both 80% [95 confidence interval (CI) 60.8% to 90.5%). The 100-day and 2-year post-transplant cumulative incidences of NRM were 3.3% (95% CI 0.2% to 14.9%) and 13.3% (95% CI 5.4% to 33.2%), respectively. The 2-year cumulative incidence of relapse was 6.7% (95% CI 1.7% to 25.4%). The cumulative incidences of grade II-IV and extensive chronic graft-versus-host disease were 27% and 14%, respectively.

Conclusions: For chemosensitive advanced high-risk B-cell lymphoma, the addition of (90)Y-Ibritumomab tiuxetan to a RIC regimen based on fludarabine, busulfan and antithymocyte globulin followed by allogeneic transplant is safe and highly effective. clinicaltrials.gov: NCT00607854.

Keywords: 90Y-ibritumomab tiuxetan; aggressive lymphoma; allogeneic stem-cell transplantation.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use*
  • Antilymphocyte Serum / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Busulfan / therapeutic use*
  • Disease-Free Survival
  • Female
  • Graft vs Host Disease
  • Humans
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / surgery
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Prospective Studies
  • Salvage Therapy
  • Stem Cell Transplantation
  • Transplantation Conditioning
  • Transplantation, Homologous
  • Treatment Outcome
  • Vidarabine / analogs & derivatives*
  • Vidarabine / therapeutic use

Substances

  • Antibodies, Monoclonal
  • Antilymphocyte Serum
  • ibritumomab tiuxetan
  • Vidarabine
  • Busulfan
  • fludarabine

Associated data

  • ClinicalTrials.gov/NCT00607854