Seminars in oncology
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Seminars in oncology · Oct 1999
ReviewOverview of the clinical development of rituximab: first monoclonal antibody approved for the treatment of lymphoma.
Rituximab (Rituxan; IDEC Pharmaceuticals, San Diego, CA, and Genentech, Inc, San Francisco, CA) is a genetically engineered monoclonal antibody for the treatment of non-Hodgkin's lymphoma. This chimeric mouse/human, immunoglobulin GI kappa anti-CD20 antibody mediates complement-dependent cell lysis and antibody-dependent cellular cytotoxicity. It also has been shown to sensitize chemoresistant human lymphoma cell lines and to induce apoptosis. ⋯ Activity also has been seen in patients with bulky disease. Combination studies have been performed with interferon, cyclophosphamide/doxorubicin/vincristine/prednisone, and radioimmunotherapy. Rituximab, the first monoclonal antibody approved for the treatment of cancer, is safe and effective in treating patients with relapsed or refractory, CD-20 positive, B-cell, low-grade or follicular non-Hodgkin's lymphoma.
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Patients with relapsed B-cell lymphomas are currently incurable with conventional doses of chemotherapy or radiotherapy. In recent years, new treatment options have become available for these patients, including the use of chimeric mouse-human anti-CD20 antibodies and radiolabeled anti-CD20 antibodies. ⋯ High-dose (131)I-anti-B1 antibody with stem cell transplantation generates objective responses in 85% to 90% of cases, including 75% to 80% complete remissions. Although more patients need to be evaluated with a longer follow-up period, radioimmunotherapy appears to be an effective and well-tolerated addition to the oncologists' armamentarium for relapsed lymphomas.
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Seminars in oncology · Oct 1999
Multicenter Study Clinical TrialCHOP plus rituximab chemoimmunotherapy of indolent B-cell lymphoma.
Indolent (low-grade) B-cell lymphomas are responsive to single-agent and combination chemotherapy agents, but unfortunately possess an incurable, relapsing nature. Novel agents and innovative treatment approaches need to be evaluated in these patients, with the ultimate goals of maintaining good quality of life and prolonging overall survival. Novel combinations of chemotherapeutic agents, monoclonal antibodies (both unlabeled and radiolabeled), and anti-idiotypic vaccine therapies are currently being evaluated. ⋯ A 95% overall response (55%, complete remission; 40%, partial remission) rate using strict definitions for complete remission and extensive staging studies was achieved in a 40-patient intent-to-treat group. In addition, seven of seven patients with follicular histologies achieving complete remission also had clearing of BCL-2 (chromosome 14;18 translocation) positivity from blood and marrow by sensitive polymerase chain reaction assay, suggesting the eradication of subclinical minimal residual disease. Based on its single-agent efficacy, excellent toxicity profile, and ability to be successfully combined with combination chemotherapy (ie, CHOP), rituximab is currently undergoing extensive investigation in a large number of worldwide clinical trials to determine its optimal use in the treatment of CD20-positive neoplasms.
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Seminars in oncology · Oct 1999
Case ReportsTreatment of plasma cell dyscrasias by antibody-mediated immunotherapy.
The use of serotherapy to treat patients with plasma cell dyscrasias (PCDs) has been sought by us and others. Candidate antigens that have been targeted or proposed for targeting in PCDs include the immunoglobulin idiotype, CD19, CD38, CD54, CD126, HM1.24, and Muc-1 core protein. Unfortunately, many of these antigens are not ideal for use in serotherapy since they are not selectively expressed, are either shed or secreted, or have not been fully characterized. ⋯ We also characterize a response to rituximab with a decrease in paraprotein and resolution of anemia in a patient with WM whose response to rituximab is ongoing after 19+ months. This preliminary experience supports the potential use of serotherapy targeting CD20 in PCDs. Our studies further suggest that interferon-gamma may enhance CD20 expression on MM plasma cells, thereby increasing their susceptibility to anti-CD20 monoclonal antibody therapies.
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Seminars in oncology · Oct 1999
Clinical TrialStem cell function and engraftment is not affected by "in vivo purging" with rituximab for autologous stem cell treatment for patients with low-grade non-Hodgkin's lymphoma.
The chimeric anti-CD20 monoclonal antibody rituximab (Rituxan; IDEC Pharmaceuticals, San Diego, CA, and Genentech, Inc, San Francisco, CA) has recently been approved by the US Food and Drug Administration as single-agent treatment of relapsed/refractory low-grade or follicular non-Hodgkin's lymphoma. Initial results from the pivotal clinical trial revealed that response rates to rituximab were higher in patients who previously had high-dose therapy and autologous stem cell transplantation. We have initiated a clinical trial that combines the use of rituximab with high-dose chemotherapy followed by autologous stem cell transplantation for patients with chemosensitive relapsed follicular small cleaved or mantle cell lymphoma. ⋯ The median number of platelet transfusions was two for patients receiving rituximab and 2.5 for the control group. Assessment of serum cytokines immediately before the rituximab infusion during the stem cell mobilization and immediately after revealed a twofold to sevenfold increase in interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6. The polymerase chain reaction analysis for minimal residual disease in stem cell collections and in peripheral blood and bone marrow samples of these patients will help to determine the efficacy of rituximab in vivo purge on disease progression.