A phase 1/2 trial of high-dose yttrium-90-ibritumomab tiuxetan in combination with high-dose etoposide and cyclophosphamide followed by autologous stem cell transplantation in patients with poor-risk or relapsed non-Hodgkin lymphoma

Blood. 2005 Oct 15;106(8):2896-902. doi: 10.1182/blood-2005-03-1310. Epub 2005 Jul 7.

Abstract

We conducted a phase 1/2 trial of high-dose 90Y-ibritumomab tiuxetan in combination with high-dose etoposide (VP-16) 40 to 60 mg/kg (day -4) and cyclophosphamide 100 mg/kg (day -2) followed by autologous stem cell transplantation (ASCT) in 31 patients with CD20+ non-Hodgkin lymphoma (NHL). Patients underwent dosimetry (day -21) with 5 mCi (185 MBq) 111In-ibritumomab tiuxetan following 250 mg/m2 rituximab, followed a week later by 90Y-ibritumomab tiuxetan to deliver a target dose of 1000 cGy to highest normal organ. Bone marrow biopsy was done on day -7 to estimate radiation dose and stem cells were reinfused when the radiation dose was estimated to be less than 5 cGy. The median 90Y-ibritumomab tiuxetan dose was 71.6 mCi (2649.2 MBq; range, 36.6-105 mCi; range, 1354.2-3885 MBq). Histology included follicular lymphoma (n = 12), diffuse large B-cell (n = 14), and mantle cell (n = 5). The median number of prior chemo-therapy treatments was 2. The treatment was well tolerated. The median times to reach an absolute neutrophil count greater than 500/microL and platelet count more than 20,000/microL were 10 days and 12 days, respectively. There were 2 deaths and 5 relapses. At a median follow-up of 22 months, the 2-year estimated overall survival and relapse-free survival rates are 92% and 78%, respectively. We conclude that high-dose 90Y-ibritumomab tiuxetan can be combined safely with high-dose etoposide and cyclophosphamide without an increase in transplant-related toxicity or delayed engraftment.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use*
  • Drug Therapy, Combination
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Etoposide / therapeutic use*
  • Female
  • Humans
  • Lymphoma, Non-Hodgkin / diagnosis*
  • Lymphoma, Non-Hodgkin / immunology
  • Lymphoma, Non-Hodgkin / surgery
  • Lymphoma, Non-Hodgkin / therapy*
  • Male
  • Middle Aged
  • Positron-Emission Tomography
  • Prognosis
  • Radioimmunotherapy*
  • Recurrence
  • Stem Cell Transplantation*
  • Survival Rate
  • Transplantation, Autologous
  • Yttrium Radioisotopes / administration & dosage
  • Yttrium Radioisotopes / adverse effects
  • Yttrium Radioisotopes / therapeutic use

Substances

  • Antibodies, Monoclonal
  • Yttrium Radioisotopes
  • ibritumomab tiuxetan
  • Etoposide
  • Cyclophosphamide