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      90Yttrium ibritumomab tiuxetan in the treatment of non-Hodgkin’s lymphoma: current status and future prospects

      review-article
      Biologics : Targets & Therapy
      Dove Medical Press
      immunotherapy, radioimmunotherapy, ibritumomab, zevalin, non-Hodgkin lymphoma

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          Abstract

          After nearly three decades with little change in the treatment for B-cell non-Hodgkin’s lymphoma, the addition of immunotherapy has had a profound effect on the treatment of this group of diseases. A more subtle addition to the armentarium has been the radiolabeled monoclonal antibodies, 90yttrium ibritumomab tiuxetan and 131iodine tositumomab. Unfortunately these drugs have been underutilized. This is, in part, because of the need for coordination between specialties, concern about long-term effects, possible limitations on the tolerance of subsequent therapies and, in part, because of reimbursement factors. In this review, the studies in relapsed and refractory disease are discussed and the very promising results reported from phase II studies using radioimmunotherapy as first-line. Potential mechanisms of resistance to monoclonal antibodies are postulated based on alterations in cell signaling pathways that have been observed in lymphoma cell lines resistant to rituximab. It is anticipated that as mechanisms of resistance are better understood for both unlabeled and labeled monoclonal antibodies, biomarkers will not only predict their efficacy but also lead to the development of therapies to overcome resistance.

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          Most cited references58

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          Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma.

          To develop guidelines for performing and interpreting positron emission tomography (PET) imaging for treatment assessment in patients with lymphoma both in clinical practice and in clinical trials. An International Harmonization Project (IHP) was convened to discuss standardization of clinical trial parameters in lymphoma. An imaging subcommittee developed consensus recommendations based on published PET literature and the collective expertise of its members in the use of PET in lymphoma. Only recommendations subsequently endorsed by all IHP subcommittees were adopted. PET after completion of therapy should be performed at least 3 weeks, and preferably at 6 to 8 weeks, after chemotherapy or chemoimmunotherapy, and 8 to 12 weeks after radiation or chemoradiotherapy. Visual assessment alone is adequate for interpreting PET findings as positive or negative when assessing response after completion of therapy. Mediastinal blood pool activity is recommended as the reference background activity to define PET positivity for a residual mass > or = 2 cm in greatest transverse diameter, regardless of its location. A smaller residual mass or a normal sized lymph node (ie, < or = 1 x 1 cm in diameter) should be considered positive if its activity is above that of the surrounding background. Specific criteria for defining PET positivity in the liver, spleen, lung, and bone marrow are also proposed. Use of attenuation-corrected PET is strongly encouraged. Use of PET for treatment monitoring during a course of therapy should only be done in a clinical trial or as part of a prospective registry.
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            Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program.

            The CD20 antigen is expressed on more than 90% of B-cell lymphomas. It is appealing for targeted therapy, because it does not shed or modulate. A chimeric monoclonal antibody more effectively mediates host effector functions and is itself less immunogenic than are murine antibodies. This was a multiinstitutional trial of the chimeric anti-CD20 antibody, IDEC-C2B8. Patients with relapsed low grade or follicular lymphoma received an outpatient treatment course of IDEC-C2B8 375 mg/m2 intravenously weekly for four doses. From 31 centers, 166 patients were entered. Of this intent-to-treat group, 48% responded. With a median follow-up duration of 11.8 months, the projected median time to progression for responders is 13.0 months. Serum antibody levels were sustained longer after the fourth infusion than after the first, and were higher in responders and in patients with lower tumor burden. The majority of adverse events occurred during the first infusion and were grade 1 or 2; fever and chills were the most common events. Only 12% of patients had grade 3 and 3% grade 4 toxicities. A human antichimeric antibody was detected in only one patient. The response rate of 48% with IDEC-C2B8 is comparable to results with single-agent cytotoxic chemotherapy. Toxicity was mild. Attention needs to be paid to the rate of antibody infusion, with titration according to toxicity. Further investigation of this agent is warranted, including its use in conjunction with standard chemotherapy.
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              New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project.

              Increasing knowledge about the biology of the non-Hodgkin's lymphomas has led to new approaches in classification. Rather than grouping lymphomas simply based on cell size, cell shape, and growth pattern, it is now possible to identify distinctive clinicopathologic entities. In many cases, the existence of specific immunologic and/or genetic features has confirmed the existence of these distinctive types of lymphoma. Since patients will be given these diagnoses by pathologists, it is important that clinicians be knowledgeable with regard to their clinical characteristics. The findings for the 13 most common lymphoma types that will be encountered in clinical practice are presented here.
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                Author and article information

                Journal
                Biologics
                Biologics: Targets & Therapy
                Biologics : Targets & Therapy
                Dove Medical Press
                1177-5475
                1177-5491
                September 2007
                September 2007
                : 1
                : 3
                : 215-227
                Affiliations
                University of Pittsburgh School of Medicine, 5150 Centre Avenue, Pittsburgh, PA, USA
                Author notes
                Correspondence: Samuel A Jacobs, University of Pittsburgh School of Medicine, 5150 Centre Avenue, Pittsburgh, PA 15232, USA, Tel +1 412 235 1278, Fax +1 412 623 4655, Email jacobssa@ 123456upmc.edu
                Article
                btt-1-215
                2721318
                19707332
                702beb3c-2913-4167-8c13-63e6bbfa8e48
                © 2007 Dove Medical Press Limited. All rights reserved
                History
                Categories
                Review

                radioimmunotherapy,zevalin,non-hodgkin lymphoma,ibritumomab,immunotherapy

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