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Drugs of interest to pathologists

Drugs related to surgical pathology

Rituximab


Author: Him G. Kwee, M.D. (see Reviewers/Authors page)
Revised: 31 March 2012, last major update March 2012
Copyright: (c) 2012, PathologyOutlines.com, Inc.

General
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● A chimeric monoclonal IgG1 kappa antibody directed against the CD20 antigen

Trade name
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● Rutixan®

Clinical information
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Approved by US Food and Drug Administration for:
● Previously untreated follicular CD20+ B cell non-Hodgkin lymphoma in combination with first line chemotherapy, in patients achieving complete or partial response to Rituxan in combination with chemotherapy and as a single agent maintenance therapy
● Nonprogressive (including stable disease) low grade CD20+ B cell non-Hodgkin lymphoma as a single agent after first line CVP chemotherapy
● Previously untreated diffuse large CD20+ B cell non-Hodgkin lymphoma in combination with CHOP or other anthracycline based chemotherapy regimens
● Relapsed or refractory low grade or follicular CD20+ B cell non-Hodgkin lymphoma as single agent
● Previously untreated and previously treated CD20+ chronic lymphocytic leukemia in combination with fludarabine and cyclophosphamide
● In combination with methotrexate in adults with moderate to severe active rheumatoid arthritis, who have had inadequate response to one or more Tissue Necrosis Factor antagonist therapies
● In combination with glucocorticoids for adults with Wegener’s granulomatosis and microscopic polyangiitis (Package insert, Rituxan, Genentech)
● Cost: 10mg/ml Concentrate 10ml Vial $700 at Drugstore.com

Rituxan side effects for pathologists
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● Post-rituxan loss of CD20 expression is associated with resistance; see Post-rituximab topic in Lymphoma - B cell neoplasms chapter
● In CLL, it is difficult to evaluate CD20 loss since it is normally expressed only dimly
● Additional B cell markers may be necessary, such as anti-CD79a, CD19 and PAX5, to detect residual disease; however CD79a antigen is expressed in a wider range of cells than CD20 and is positive in plasma cells
● CD19 can also be positive in T cell lymphomas
● After Rituxan therapy, T cell aggregates may be seen in bone marrow; CD3, CD19 or CD79a may be needed to distinguish these non-neoplastic T cell aggregates from residual B cell lymphoma (Appl Immunohistochem Mol Morphol 2009;17:96)
● Rituxan persists for many months in serum after therapy and is cytotoxic in the presence of complement
● This condition can cause a positive B cell cytotoxic positive crossmatch in testing for transplantation purposes
● The human portion of IgG1 in Rituxan is also a target for the anti-human Ig fluorochromes used in flow cytometric crossmatches and could result in a false positive B cell crossmatch
● Flow and cytotoxic crossmatches can be done if the CD20 is eliminated first with pronase treatment of the cells, or if the Rituxan is removed with immununomagnetic bead absorption (Am J Transplant 2006;6:859)
● The boxed warning of the drug includes the possibility of progressive multifocal leukoencephalopathy as a side effect (Package insert, Rituxan, Genentech)

End of Drugs > Drugs related to surgical pathology > Rituximab


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