A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma

Cancer. 2012 Oct 1;118(19):4706-14. doi: 10.1002/cncr.27418. Epub 2012 Jan 17.

Abstract

Background: High-dose chemotherapy combined with autologous stem-cell transplantation (ASCT) is the standard therapy for refractory/relapsed aggressive lymphoma. In the era of rituximab-containing frontline regimens, it is becoming more challenging to salvage patients in this setting, and novel approaches are required. This is a randomized study evaluating the safety and efficacy of standard-dose ibritumomab tiuxetan (Zevalin) combined with high-dose BEAM chemotherapy (Z-BEAM) and ASCT in refractory/relapsed aggressive lymphoma.

Methods: Forty-three patients with CD20(+) -aggressive lymphoma were randomized to a treatment arm (Z-BEAM, n = 22) or control arm (BEAM alone, n = 21). Ibritumomab tiuxetan was given at 0.4 mCi/kg on day -14 before ASCT.

Results: Patient characteristics, engraftment kinetics, and toxicity profile were similar between the 2 groups. Two-year progression-free survival (PFS) for all patients was 48% (95% confidence interval, 32%-64%): 59% and 37% after Z-BEAM and BEAM alone, respectively (P = .2). Multivariate analysis identified advanced age (hazard ratio [HR], 8.3; P = .001), high-risk disease (relapse within 12 months of diagnosis and/or secondary International Prognostic Index >2; HR, 2.8; P = .04), positive positron emission tomography-computed tomography pretransplant (HR, 2.4; P = .07), and BEAM alone (HR, 2.8; P = .03) as poor prognostic factors. Intermediate-risk patients with 1 or 2 risk factors had better PFS with Z-BEAM compared with BEAM: 69% and 29%, respectively (P = .07). Two-year overall survival was 91% and 62% after Z-BEAM and BEAM, respectively (P = .05). Similar prognostic factors determined survival. The HR for BEAM alone in the multivariate analysis was 8.1 (P = .01).

Conclusions: Standard-dose ibritumomab tiuxetan combined with BEAM high-dose chemotherapy is safe and possibly more effective than BEAM alone as a conditioning regimen for ASCT in the era of rituximab-containing chemotherapy regimens.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carmustine / administration & dosage
  • Cytarabine / administration & dosage
  • Disease-Free Survival
  • Drug Administration Schedule
  • Early Termination of Clinical Trials
  • Etoposide / administration & dosage
  • Female
  • Humans
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / mortality
  • Lymphoma, Non-Hodgkin / surgery*
  • Male
  • Melphalan / administration & dosage
  • Middle Aged
  • Odds Ratio
  • Prognosis
  • Proportional Hazards Models
  • Recurrence
  • Risk Factors
  • Sample Size
  • Stem Cell Transplantation*
  • Survival Analysis
  • Transplantation Conditioning / methods*
  • Transplantation, Autologous
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Cytarabine
  • ibritumomab tiuxetan
  • Etoposide
  • Melphalan
  • Carmustine

Supplementary concepts

  • BEAM regimen