Rituximab disease

Chronic lymphocytic leukemia (CLL) patients who receive fludarabine-based combination chemotherapy and rituximab may have long-term disease-free survival. 

Combination therapy may provide improvement in longterm disease-free survival. The combination of fludarabine, cyclophosphamide, and rituximab improves CR rates compared with fludarabine alone (70% versus 20%) but at the expense of increased infections.28,29 Combinations of fludarabine and alemtuzumab are also being investigated, with the hope of improving overall survival.21... 

Rituximab -monoclonal antibody to CD20 (B-cell surface antigen) -fever, chills, malaise -nausea, vomiting -flushing -bronchospasm, angioedema, urticaria -rhinitis -pain at disease sites -tumor lysis syndrome may occur in patients with high peripheral lymphocyte count... 

Rituximab, a chimeric monoclonal antibody directed at the CD20 molecule on B cells, has become one of the most widely used therapies for follicular lymphoma. Rituximab is approved for first-line therapy either alone or combined with chemotherapy and as maintenance therapy for patients with stable disease or with partial or complete response following induction chemotherapy. 

The rituximab dosage is 375 mg/m2 weekly for 4 weeks. Maintenance schedules include 375 mg/m2 weekly for 4 weeks every 6 months for 2 years or 375 mg/m2 every 2 to 3 months for 1 to 2 years. Maintenance rituximab significantly prolongs progression-free and overall survival as compared with observation or initiation of rituximab at the time of disease progression. 

In addition, combination therapy trials of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in refractory and newly diagnosed patients suggests that rituximab may also have a role in the eradication of residual disease. This combination appears to be a viable treatment option for relapsed low-grade non-Hodgkin lymphoma... 

Examples of antibodies in the market include trastuzumab (anti-HER2 monoclonal antibody), rituximab, natalizumab (x4-integiin antibody), abciximab, infiximab (targets TNF-a in Crohn s disease and rheumatoid arthritis), alemtuzumab, adalimumab (TNF-a antibody for the treatment of rheumatoid arthritis) and efalizumab (anti-CDlla monoclonal antibody for the treatment of psoriasis)Rituximab is a mouse/human chimeric anti-CD20 monoclonal antibody used for the treatment of various l)unphoid malignancies. As CE)20 antigen is found on the surface of... 

Kazkaz H, Isenberg D. Anti B cell therapy (rituximab) in the treatment of autoimmune diseases. Curr Opin Pharmacol 2004 4 398 02. 

Based on the bio-molecular pathogenesis, novel therapeutic agents have been developed since 1998 for the treatment of DMARDs refractory autoimmune diseases. These biological-DMARDs include infliximab, etanercept, adalimumab, rituximab and abatacept. The biological-DMARDs anti TNF-a were first approved for therapy of refractory RA, followed by Crohn s disease, AS, and PsA. Scores of other biological DMARDs in Phase I, II, and III clinical trials in autoimmune diseases indicate that the number of these biological agents may ultimately become equal to the number of NSAIDs introduced over the last 50 years. 

Rituxan was administered at weekly intervals for four doses to NHL patients, the peak and trough serum levels of rituximab were inversely correlated with baseline values for the number of circulating CD20 positive B cells and measures of disease burden. Median steady-state serum levels were higher for responders compared to nonresponders. Rituximab was detectable in the serum of patients 3 to 6 months after completion of treatment. 

Ibritumomab tiuxetan is an anti-CD20 murine monoclonal antibody labeled with isotopic yttrium (90Y) or 11 LIn. The radiation of the isotope provides the major antitumor activity. Ibritumomab is approved for use in patients with relapsed or refractory low-grade, follicular, or -cell non-Hodgkin s lymphoma, including patients with rituximab-refractory follicular disease. It is used in conjunction with rituximab in a two-step therapeutic regimen. 

Tositumomab is another anti-CD20 monoclonal antibody and is complexed with iodine 131 (131I). Tositumomab is used in two-step therapy in patients with CD20-positive, follicular non-Hodgkin s lymphoma whose disease is refractory to rituximab and standard chemotherapy. Toxicities are similar to those for ibritumomab and include severe cytopenias such as thrombocytopenia and neutropenia. Tositumomab should not be administered to patients with greater than 25% bone marrow involvement. 

Combination chemotherapy is the treatment standard for patients with diffuse non-Hodgkin s lymphoma. The anthracycline-containing regimen CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) has been considered the best treatment in terms of initial therapy. Recently, randomized phase III clinical studies have shown that the combination of CHOP with the anti-CD20 monoclonal antibody rituximab results in improved response rates, disease-free survival, and overall survival compared with CHOP chemotherapy alone. 

Following the success of recombinant proteins such as insulin, therapeutic mAbs today represent the second wave of innovation created by the biotechnology industry during the past 20 years. The recent success of a number of new mAb therapies, for example rituximab (Rituxan ) and infliximab (Remicade ), suggests a resurgence of the biotech industry for the coming years. For serious chronic diseases such as cancer or rheumatoid arthritis, mAb therapy has indeed proven its clinical efficacy. 

A large multicenter pivotal phase II study was performed to evaluate the efficacy of rituximab in the treatment of relapsed low-grade or follicular CD20(+) B-cell NHL (171). A total of 166 patients with small lymphocytic (n= 33), follicular small cleaved (n = 67), follicular mixed (n= 53), follicular large-cell (n = 10), or low-grade variant (n = 3) NHL were enrolled at 31 centers. Patients with bulky disease (>10 cm), pleural or peritoneal involvement, CNS lymphoma, AIDS-related lymphoma, CLL or leukemic component (more than 5,000 lymphocytes/pl) were excluded. Rituximab was again administered intravenously at 375 mg/m2 weekly for four doses. The overall response rate, which was the primary study end point, was... 

Salama AD, Pusey CD. Drag insight rituximab in renal disease and transplantation. Nat Clin Pract Nephrol 2006 2 221-30. 

Current phase I/II trials in PP-MS are underw ay and include evaluation of rituximab, a synthetic antibody that binds to and induces lyses of B cells. The trial is scheduled to enroll over 430 patients for 30m and will monitor clinical outcomes as well as immunologic and MRI measures. Rationale for the trial is based on a efficacy in use with worsening Devic s disease or neuromyelitis optica (Cree et al., 2005). 

Rituximab Fever chills rigors hypotension bronchospasm Bone marrow depression angioedema precipitation of angina or arrhythmia with pre-existing heart disease... 

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