Seminars in oncology
-
Research in chronic lymphocytic leukemia (CLL) has undergone a resurgence of interest in the last decade. While it is obvious that most patients with CLL have typical mature B cells, a number of variants such as splenic lymphoma villous lymphocytes, mantle cell leukemia, and prolymphocytic leukemia need to be considered in the differential diagnosis. This can be established by immunophenotype studies and morphology. ⋯ Campath-1H is emerging as another major antibody with marked effect against disease, particularly in the blood and bone marrow. Autologous, allogeneic, and mini-transplant are also being explored extensively. The prognosis for patients with CLL is changing as these new treatments become available.
-
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.
-
The CD20 antigen is an attractive target for antibody-directed therapy due to its stable, high-level surface expression on normal and malignant B cells. Rituximab (Rituxan; IDEC Pharmaceuticals, San Diego, and Genentech, Inc, San Francisco, CA) is an anti-CD20 chimeric monoclonal antibody that has shown single-agent activity in phase I and II clinical trials in patients with B-cell non-Hodgkin's lymphoma. This antibody has a long serum half-life and low immunogenicity. ⋯ The mechanism of action likely includes both immune-mediated effects and direct effects. The generally mild toxicity profile and excellent single-agent activity provide the rationale for use with or following chemotherapy. Additional studies evaluating these and other combinations are under way.
-
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.
-
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.