Iodine-131 rituximab radioimmunotherapy with BEAM conditioning and autologous stem cell transplant salvage therapy for relapsed/refractory aggressive non-Hodgkin lymphoma

Cancer Biother Radiopharm. 2012 Nov;27(9):552-60. doi: 10.1089/cbr.2012.1275. Epub 2012 Oct 12.

Abstract

A standard salvage therapy of relapsed/refractory aggressive non-Hodgkin lymphoma (NHL) comprises autologous stem cell transplantation (ASCT) after chemotherapy conditioning with carmustine, etoposide, cytarabine, and melphalan (BEAM) regimen. However, the achievement of long-term disease-free survival remains challenging. We have introduced concomitant (131)I-rituximab radioimmunotherapy (RIT) in an attempt to effect the elimination of lymphoma cells. Our phase II physician-sponsored study of 16 consecutive patients with relapsed, refractory, aggressive B-cell NHL reports a median 44 month follow-up after (131)I-rituximab-BEAM conditioning therapy and ASCT. Prospective personalized dosimetry performed in each patient limited the whole body radiation absorbed dose to 0.75 Gy. RIT (131)I-rituximab was administered on an outpatient basis on day -15 before ASCT. The BEAM conditioning regimen was commenced on day -6. Evaluable engraftment data are available for 15 patients who had 16 ASCTs. Engraftment was achieved in all patients, 15 out of 16 ASCTs achieved a complete response, and 1 out of 15 ASCTs achieved a partial response. Twelve out of sixteen patients remained alive and disease free at a median of 44 months (range 4-108 months) post-ASCT. This study suggests that the addition of (131)I-rituximab RIT to BEAM conditioning, before ASCT, for relapsed or primary refractory B-cell NHL improves disease eradication, compared with BEAM conditioning alone, without significant additional toxicity. In particular, there is an impression of improved disease control in the subset of patients with transformed follicular and mantle cell lymphomas.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage*
  • Antibodies, Monoclonal, Murine-Derived / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carmustine / administration & dosage
  • Cytarabine / administration & dosage
  • Disease-Free Survival
  • Etoposide / administration & dosage
  • Humans
  • Iodine Radioisotopes / administration & dosage*
  • Iodine Radioisotopes / adverse effects
  • Lymphoma, Non-Hodgkin / drug therapy
  • Lymphoma, Non-Hodgkin / radiotherapy
  • Lymphoma, Non-Hodgkin / surgery
  • Lymphoma, Non-Hodgkin / therapy*
  • Melphalan / administration & dosage
  • Middle Aged
  • Radioimmunotherapy / methods*
  • Rituximab
  • Salvage Therapy / methods
  • Stem Cell Transplantation / methods*
  • Transplantation Conditioning / methods*
  • Transplantation, Autologous

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Iodine Radioisotopes
  • Cytarabine
  • Rituximab
  • Etoposide
  • Melphalan
  • Carmustine

Supplementary concepts

  • BEAM regimen