Abstract
The development of monoclonal antibodies has dramatically changed the outcome of patients with non-Hodgkin’s lymphoma (NHL), the most common hematological malignancy. However, despite the satisfying results of monoclonal antibody treatment, only few NHL patients are permanently cured with single-agent therapies. In this context, radioimmunotherapy, the administration of radionuclides conjugated to monoclonal antibodies, is aimed to augment the single-agent efficacy of immunotherapy in order to deliver targeted radiation to tumors, particularly CD20+ B-cell lymphomas. Based on evidence from several trials in NHL, the radiolabeled antibodies 90Y-ibritumomab tiuxetan (Zevalin, Spectrum Pharmaceuticals) and 131I-tositumomab (Bexxar, GlaxoSmithKline) received FDA approval in 2002 and 2003, respectively. However, none of the two radioimmunotherapeutic agents has been broadly applied in clinical practice. The main reason for the under-utilization of radioimmunotherapy includes economic and logistic considerations. However, concerns about potential side effects have also been raised. Driven by these developments, we performed retrospective analysis of adverse events reporting Zevalin or Bexxar, extracted from the FDA’s Adverse Event Reporting System (FAERS) and the World Health Organization’s VigiBase repository. Our results indicate that the two radioimmunotherapeutic agents have both related and distinct side effect profiles and confirm their known toxicological considerations. Our work also suggests that computational analysis of real-world post-marketing data can provide informative clinical insights. While more prospective studies are necessary to fully characterize the efficacy and safety of radioimmunotherapy, we expect that it has not yet reached its full therapeutic potential in modern hematological oncology.
Highlights
The development and introduction of monoclonal antibodies in clinical practice have constituted a true revolution in the management of non-Hodgkin’s lymphoma (NHL), the most frequent hematologic malignancy
Our dataset consisted of adverse events (AEs) extracted from Food and Drug Administration (FDA)’s Adverse Event Reporting System (FAERS) and VigiBase that reported use of Bexxar or Zevalin
As expected, ‘non-Hodgkin’s lymphoma’, as well as other Preferred Term (PT) describing—more or less specific—forms of lymphoma were reported as treatment indication in the vast majority of the reported cases in all cohorts
Summary
The development and introduction of monoclonal antibodies in clinical practice have constituted a true revolution in the management of non-Hodgkin’s lymphoma (NHL), the most frequent hematologic malignancy. Rituximab is directed against the CD20 antigen and exerts its antitumor effect by activation of antibody-dependent cell-mediated cytotoxicity through complement activation and induction of apoptosis [2]. Despite the satisfying results of monoclonal antibody treatment, only few patients are permanently cured with single-agent therapy: fewer than half of follicular NHL patients respond to Rituximab with median response duration of about a year, since they may not respond or may develop resistance to antibody therapy [3,4]. Radioimmunotherapy represents an attempt to augment the single-agent efficacy of this therapeutic approach in NHL by conjugating therapeutic radionuclides to the monoclonal antibodies in order to deliver radiation to these tumors [5], which are known to be more radiosensitive than solid tumors and other types of cancer [6,7,8,9]. Due to the “crossfire” radiation effect, adjacent tumor cells that do not bind the antibody may still be killed [5]
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