Abstract
Purpose: Both anti-CD20 antibodies (ibritumomab; ZEVALIN® and tositumomab; BEXXAR®) currently used for radioimmunotherapy of B cell non-Hodgkin's lymphoma are murine immunoglobulins. The aim of this feasibility study was to evaluate the safety and efficacy of radioimmunotherapy with a human chimeric anti-CD20 antibody labelled with Yttrium-90 ( 90 Y-rituximab) in patients with B cell lymphoma. Methods: Patients with CD20+ B-cell lymphoma in partial remission or with progressive disease after at least one line of therapy were included. 90 Y-rituximab was administered according to a similar schedule as currently approved by the European Medicines Agency for the treatment with 90 Y-ibritumomab tiuxetan (ZEVALIN ® ): a first infusion of rituximab 250 mg/m² is repeated one week later and directly followed by the injection of 90Y-rituximab (14,8 MBq/kg). 18 FDG-PET/CT was performed before treatment and repeated 3 months after for response assessment. Results: Twenty-six patients were treated with 90 Y-rituximab. Disease histologies included mainly follicular lymphomas (53%). Toxicity was primarily haematological. The incidence of grade 3-4 neutropenia, thrombocytopenia and anemia were 34%, 38%, and 8% respectively, with spontaneous recovery in all but one patient that needed autologous stem cell transplant for refractory thrombocytopenia. Among the relevant long-term side effects, one patient developed secondary myelodysplasia 2 years after the treatment. The overall response rate was 88% (95% CI: 70%-98%), including 65% complete metabolic responses and 23% partial metabolic responses. After a median follow-up of 29.6 months, the Kaplan-Meier estimated median progression-free survival was 9.1 months (95% CI 6.1-17.9). Median time to next treatment was 24 months (95% CI: 12.8-28).
Highlights
Radioimmunotherapy (RIT) is a targeted molecular radiotherapy in which radiation from radionuclides is delivered selectively to tumours by using monoclonal antibodies directed to tumour-associated antigens
Patients with CD20+ B-cell lymphoma in partial remission or with progressive disease after at least one line of therapy were included. 90Y-rituximab was administered according to a similar schedule as currently approved by the European Medicines Agency for the treatment with 90Y-ibritumomab tiuxetan (ZEVALIN®): a first infusion of rituximab 250 mg/m2 is repeated one week later and directly followed by the injection of 90Y-rituximab (14,8 MBq/kg). 18FDG-PET/CT was performed before treatment and repeated 3 months after for response assessment
The most widely studied radioimmunoconjugates for treatment of B cell Non-Hodgkin’s Lymphoma (NHL) are murine anti-CD20 monoclonal antibodies radiolabelled with Yttrium-90 (90Y-ibritumomab tiuxetan; ZEVALIN®) or Iodine-131 (131I-tositumomab; BEXXAR®)
Summary
Radioimmunotherapy (RIT) is a targeted molecular radiotherapy in which radiation from radionuclides is delivered selectively to tumours by using monoclonal antibodies directed to tumour-associated antigens. The most widely studied radioimmunoconjugates for treatment of B cell Non-Hodgkin’s Lymphoma (NHL) are murine anti-CD20 monoclonal antibodies radiolabelled with Yttrium-90 (90Y-ibritumomab tiuxetan; ZEVALIN®) or Iodine-131 (131I-tositumomab; BEXXAR®). Several studies have shown the efficacy of these radioimmunoconjugates in patients with B cell NHL, as a single agent in indolent lymphoma and in combination with chemotherapy in both indolent and aggressive lymphoma [1,2,3,4,5,6]. In Europe, only 90Y-ibritumomab tiuxetan (ZEVALIN®) has been approved, and this radioimmuno conjugate is used in combination with unlabeled rituximab. Rituximab (RITUXAN® or MABTHERA®), a chimeric IgG1 Kappa monoclonal antibody, targets the same epitope on the CD20 antigen. J Cancer Sci Ther 4: 394-400. doi:10.4172/1948-5956.1000173
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