Radioimmunotherapy for patients with relapsed B-cell non-Hodgkin lymphoma

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Clinical trials of an yttrium-90 (90Y)-conjugated monoclonal antibody to CD20 in patients with relapsed B cell non-Hodgkin lymphoma (NHL) are reviewed. Ibritumomab is the murine parent anti-CD20 antibody engineered to make the human chimeric antibody rituximab. Tiuxetan is an MX-DTPA linker chelator attached to ibritumomab to form ibritumomab tiuxetan (Zevalin). Ibritumomab tiuxetan can react with indium-111 (111In) or 90Y to form 111In-ibritumomab tiuxetan, which is used for dosimetry, or 90Y-ibritumomab tiuxetan, which is used for therapy of B cell NHL. In this report, the results of five separate clinical trials of ibritumomab tiuxetan are reviewed. Two phase I trials of 90Y-ibritumomab tiuxetan were performed, one using cold ibritumomab prior to 90Y-ibritumomab tiuxetan, and one using rituximab prior to 90Y-ibritumomab tiuxetan. The optimal schedule was found to be rituximab on days 1 and 8, and 90Y-ibritumomab tiuxetan 0.4 mCi/kg i.v. on day 8; no stem cells or prophylactic growth factors were used. A dose of 0.3 mCi/kg was recommended for patients with a baseline platelet count of 100,000-149,000×106/l. The only significant toxicity was reversible myelosuppression. With this schedule, the overall response rate (ORR) was 67% of all patients and 82% of those with low-grade NHL. The phase I/II trials were followed by a phase III trial that randomized 143 eligible patients to either rituximab or 90Y-ibritumomab tiuxetan radioimmunoconjugate to demonstrate that the combination of the 90Y radioisotope to the murine anti-CD20 antibody provided additional efficacy over the unconjugated ("cold") rituximab alone. A planned interim analysis of the first 90 patients demonstrated an ORR of 80% with 90Y-ibritumomab tiuxetan vs 44% for rituximab (P < 0.05). To provide additional evidence of the benefit of 90Y radioimmunotherapy over rituximab immunotherapy, patients who were nonresponsive or refractory to rituximab were enrolled in an additional trial and treated with 90Y-ibritumomab tiuxetan 0.4 mCi/kg. An ORR of 46% was achieved in these rituximab-refractory patients. These results provide further evidence of the added value of 90Y. Therefore 90Y-ibritumomab tiuxetan radioimmunotherapy is a useful new treatment modality for patients with B cell NHL. Future trials are needed to define the optimal time in the disease course when this modality should be used.

Original languageEnglish (US)
JournalCancer Chemotherapy and Pharmacology
Volume48
Issue numberSUPPL. 1
DOIs
StatePublished - 2001

Fingerprint

Radioimmunotherapy
B-Cell Lymphoma
Non-Hodgkin's Lymphoma
Cells
ibritumomab tiuxetan
Refractory materials
Antibodies
Anti-Idiotypic Antibodies
Appointments and Schedules
Clinical Trials
Immunoconjugates
Yttrium
Rituximab
Pentetic Acid
Indium
Chelating Agents
Platelets
Stem cells
Platelet Count
Radioisotopes

Keywords

  • CD20
  • Monoclonal antibody
  • Non-Hodgkin lymphoma
  • Radioimmunotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology

Cite this

Radioimmunotherapy for patients with relapsed B-cell non-Hodgkin lymphoma. / Witzig, Thomas Elmer.

In: Cancer Chemotherapy and Pharmacology, Vol. 48, No. SUPPL. 1, 2001.

Research output: Contribution to journalArticle

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