Rituximab

Alemtuzumab is a humanized antibody that is directed against the cell-surface glycoprotein expressed on the surface of the normal and malignant B and T lymphocytes, and is indicated for the treatment of B-cell CLL [91]. 

Bevacizumab, a humanized IgG and cetuximab, a chimeric IgGx, are currently marketed in the US for treatment of metastatic colorectal cancer [92, 93]. Bevacizumab neutralizes the biological activity of vascular endothelial growth factor (VEGF), while cetuximab binds specifically to the extracellular domain of the human epidermal growth factor receptor (EGFR). Bevacizumab, in combination with IV 5-fluorouracil (5-FU) -based chemotherapy, is indicated for first-line treatment of metastatic colorectal cancer, whereas cetuximab is used in patients refractory to or intolerant to irinotecan-based chemotherapy. The clinical pharmacokinetics of cetuximab are discussed in detail in Chapter 14. 

Rituximab is a chimeric antibody that contains the human IgGx constant region and murine variable region, and binds the membrane-associated human CD20 antigen. Evidence for multiple mechanisms of rituximab action has been reported [96, 97]. Rituximab can deplete CD20-positive B cells via ADCC, CDC, or apoptosis however, it is not clear which is the most important mechanism in humans. Resistance to rituximab s in-vivo effects has been reported, but the underlying resistance mechanisms are not well understood. 

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Recombinant humanized monoclonal antibodies have been used recently to target antigens that are preferentially located on cancer cells. Examples include trastuzumab and rituximab which are used to treat HER2 positive breast cancer and B-cell type lymphomas, respectively. Unwanted side effects include anaphylactic reactions. 

The potential of B lymphocyte depletion as an approach to therapy has been confirmed in RA patients seropositive for rheumatoid factor and/or anti-CCP antibodies using the anti-CD20 mAb, rituximab. 

Rituximab is a recombinant mouse/human chimeric monoclonal antibody whose in vitro activity varies with the number of terminal galactose moieties glycosylated to the peptide backbone at residue asparagine 301 [8]. The ability to monitor the levels of each discrete species present would allow the manufacturing process to... 

Figure 5.9 Principal oligosaccharide structures found on recombinant rituximab. Reprinted from J. Chromatogr., A, 913, Wan, H. Z., Kaneshiro, S., Frenz, J. and Cacia, J., Rapid method for monitoring galactosylation levels dnring recombinant antibody production by electrospray mass spectrometry with selective-ion monitoring , 437-446, Copyright (2001), with permission from Elsevier Science.

Also known as antibody-mediated rejection, humoral rejection is the process of creating graft-specific antibodies.1,4 This type of rejection occurs less frequently than cell-mediated acute rejection. Humoral rej ection is characterized by deposition of immunoglobulins and complement in allograft tissues. Treatment for this type of rejection is not well defined, yet several reports have shown that treatments such as plasmapheresis, immunoglobulin therapy, rituximab, and/or antithymocyte globulin maybe effective. 

Rituximab (Rituxan) Two 1000-mg infusions separated by 2 weeks IV infusion 4 weeks IR Monitor for infection ... 

The exact role of rituximab in RA is not clearly defined, but it is indicated for patients with moderate to severe RA with a history of inadequate response to DMARDs and other BRMs. Rituximab carries a black-box warning of fatal infusion reactions and severe mucocutaneous reactions even though these events did not occur during the RA clinical trials. The benefits of rituximab must be tempered against the safety concerns reported with use of rituximab in the oncology setting. 

This hot antibody is linked to yttrium and binds to the CD20 receptor of B lymphocytes (see Rituximab below). Hematologic toxicity may occur several weeks after administration and may take weeks to resolve. 

Rituximab is a monoclonal antibody to the CD20 receptor expressed on the surface of B lymphocytes the presence of the antibody is determined during flow cytometry of the tumor cells. Cell death results from antibody-dependent cellular cytotoxicity. The pharmacokinetics of rituximab are best described by a two-compartment model, with a terminal half-life of 76 hours after the first infusion and a terminal half-life of 205 hours after the fourth dose.36 Rituximab has shown clinical activity in the treatment of B-cell lymphomas that are CD20+. Side effects include hypersensitivity reactions, hypotension, fevers, chills, rash, headache, and mild nausea and vomiting. 

The recombinant monoclonal antibody rituximab is an effective treatment option for some patients with non-Hodgkin s lymphoma as a single agent and enhances the efficacy of combination chemotherapy regimens. 

The addition of rituximab to chemotherapy has an adverse effect on outcome in this patient population. 

A limitation of rituximab treatment is the severe and potentially fatal infusion-related reactions. To date, eight deaths have... 

Coiffer B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large B-cell lymphoma. New Engl J Med 2002, 346 235-242. 

McLaughlin P, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma Half of patients respond to a four dose treatment program. J Clin Oncol 1998 16 2825-2833. 

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

Rituximab (Rituxan ) Rituximab is a chimeric monoclonal antibody directed against the CD20 molecule on B lymphocytes.21 Similar to other B-cell malignancies, CLL... 

Rituximab Infusion reactions fever, chills, rigors, Premedicate with acetaminophen, diphenhydramine,... 

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... 

Watch for infusion reactions with rituximab and alemtuzumab. Premedicate with acetaminophen and diphenhydramine to prevent these reactions. 

LL, a 47-year-old man, was diagnosed with high-risk diffuse large cell B-cell non-Hodgkin s lymphoma (NHL) 12 months ago. LL had a complete response to his initial treatment of six cycles of RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). LL is participating in a clinical trial and is randomized to receive a myeloablative autologous HCT TBI days 8 to 5, etoposide day 4, rest day 3, cyclophosphamide day 2, rest day 1, with infusion of autologous PBPC on day 0. 

BR arrives at the clinic to receive her first dose of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) at full doses. 

Rituxan Rituximab Genentech Treatment of relapsed or refractory low-grade or follicular CD20-positive B-cell non-Hodgkins lymphoma... 

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