Yttrium-90-ibritumomab tiuxetan in combination with intravenous busulfan, cyclophosphamide, and etoposide followed by autologous stem cell transplantation in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma

Invest New Drugs. 2010 Aug;28(4):516-22. doi: 10.1007/s10637-009-9283-z. Epub 2009 Jun 23.

Abstract

Background: Radiolabelled immunotherapy agents have an increasingly significant role in autologous stem cell transplantation (ASCT) by improving the tolerability and increasing the efficacy of the conditioning regimen, thereby reducing the relapse risk. We evaluated the efficacy and safety of yttrium-90-ibritumomab tiuxetan ((90)Y-ibritumomab) combined with intravenous busulfan, cyclophosphamide, and etoposide (Bu/Cy/E) followed by ASCT in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL).

Methods: Each patient received a single dose of (90)Y-ibritumomab (0.4 mCi/kg on day -14) with Bu/Cy/E as a conditioning regimen.

Results: The patient cohort consisted of 19 individuals (ten males), of median age 51 years (range, 25-63 years). Sixteen patients had received two or more chemotherapy regimens before transplantation. Histologies were diffuse large B-cell (n = 14), follicular (n = 2), mantle cell (n = 2), and Burkitt lymphoma (n = 1). All patients engrafted. The median time to neutrophil engraftment was 10 days and time to platelet engraftment was 10 days. Nineteen patients were evaluable for response. The objective overall response rate was 84.2% (16/19): continued CR, 36.8% (7/19); induced CR, 36.8% (7/19); and PR, 10.5% (2/19). With a median follow-up of 29.4 months (13.4-36.6), the estimated 3-year overall survival and event-free survival rates were 52.6% (95% confidence interval [CI] 45.8-59.4) and 26.3% (95% CI 19.8-32.8), respectively. Adverse events were similar to those seen historically with Bu/Cy/E alone, and there were no treatment related deaths.

Conclusion: In conclusion, (90)Y-ibritumomab with Bu/Cy/E and ASCT is feasible in patients with relapsed or refractory B-cell NHL, without increased toxicity.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Busulfan / administration & dosage
  • Busulfan / adverse effects
  • Combined Modality Therapy / methods
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Disease-Free Survival
  • Drug Administration Schedule
  • Drug Resistance, Neoplasm / drug effects*
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / prevention & control*
  • Lymphoma, B-Cell / therapy*
  • Male
  • Middle Aged
  • Secondary Prevention
  • Transplantation Conditioning / methods
  • Transplantation, Autologous / methods

Substances

  • Antibodies, Monoclonal
  • ibritumomab tiuxetan
  • Etoposide
  • Cyclophosphamide
  • Busulfan