Myeloablative anti-CD20 radioimmunotherapy +/- high-dose chemotherapy followed by autologous stem cell support for relapsed/refractory B-cell lymphoma results in excellent long-term survival

Oncotarget. 2013 Jun;4(6):899-910. doi: 10.18632/oncotarget.1037.

Abstract

Background: Radioimmunotherapy (RIT) has been used to treat relapsed/refractory CD20+ Non-Hodgkin lymphoma (NHL). Myeloablative anti-CD20 RIT followed by autologous stem cell infusion (ASCT) enables high radiation doses to lymphoma sites. We performed a phase I/II trial to assess feasibility and survival.

Methods: Twenty-three patients with relapsed/refractory NHL without complete remission (CR) to salvage chemotherapy were enrolled to evaluate RIT with Iodine-131 labelled rituximab (131I-rituximab) in a myeloablative setting. Biodistribution and dosimetric studies were performed to determine 131I activity required to induce a total body dose of 21-27Gy to critical organs. In 6/23 patients RIT was combined with high-dose chemotherapy. 8/23 patients received a sequential high-dose chemotherapy with a second ASCT. The median follow-up is 9.5 years.

Results: 6.956-19.425GBq of 131I was delivered to achieve the limiting organ dose to lungs or kidneys. No grade III/IV non-hematologic toxicity was seen with RIT alone. Significant grade III/IV toxicity (mucositis, fever, infection, one therapy related death) was observed in patients treated with RIT combined with high-dose chemotherapy. The overall response rate was 87% (64% CR). The median progression-free (PFS) and overall survival (OS) is 47.5 and 101.5 months. An international prognostic index score >1 was predictive for OS.

Conclusion: Myeloablative RIT with 131I-rituximab followed by ASCT is feasible, well-tolerated and effective in high risk CD20+ NHL. Combination of RIT and high-dose chemotherapy increased toxicity significantly. Long-term results for PFS and OS are encouraging.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Combined Modality Therapy
  • Disease-Free Survival
  • Female
  • Humans
  • Iodine Radioisotopes / administration & dosage
  • Lymphoma, B-Cell / pathology
  • Lymphoma, B-Cell / therapy*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / therapy
  • Peripheral Blood Stem Cell Transplantation / methods
  • Radioimmunotherapy / methods*
  • Radiopharmaceuticals / administration & dosage
  • Risk Factors
  • Rituximab
  • Survival Analysis
  • Transplantation, Autologous / methods

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • Rituximab