Rituximab (Rituxan)

Anti-CD 20 monoclonal antibody targets CD20 B-cells by recruiting Fc receptor-expressing cellular effectors of natural killer cells and macrophages able to mediate antibody-dependent cellular cytotoxicity, causes cell growth cell arrest and promotes apoptosis.

Antibody induces cell death by complement dependent cytotoxicity and antibody dependent cell mediated cytotoxicity.

Induces apoptosis and sensitizes cells to the effects of chemotherapy.

Chimeric monoclonal antibody directed against CD20 antigen which is expressed on pre-B and mature B cell lymphocytes.

Pharmacokinetics similar to that of human IgG, whether given weekly, monthly it is present at therapeutic levels in the circulation for months at a time.

As with IgG it distributes in the intravascular and extravascular compartments.

Intravenous administration can cause severe reactions.

Severe reactions typically occur with the first infusion (80%), with an onset of 30-120 minutes of starting the infusion.

Hypersensitivity reactions include hypotension, angioedema, urticaria, hypoxia, bronchospasm, lung infiltrates, acute respiratory distress, myocardial infarction, ventricular fibrillation, cardiogenic shock, and anaphylaxis.

Rarely, deaths have been reported within 24 hours of infusion of this drug.

Resistance to this agent occurs in about half of patients with NHL, resulting in non-response to treatment or early relapse of the original disease.

Eliminates CD20+ cells mainly by three mechanisms: complement dependent cytotoxicity, antibody depenedent cellular cytotoxicity, and induction of apoptosis.

Some studies suggest this agent may contribute to T-cell response, the vaccinal effect, in which the death of follicular lymphoma cells caused a T cell specific response to follicular lymphoma cells (Hagenbeek A et al).

Complement is activated in some patients treated with this drug, but not all patients, and complement activation correlates with infusional toxicity (van der Kolk LE).

Rituximab is used to treat cancers of the white blood system such as leukemias and lymphomas, including non-Hodgkin’s lymphoma and lymphocyte predominant subtype, of Hodgkin’s Lymphoma.

Shown to be an effective rheumatoid arthritis treatment.

It has been FDA-approved for use in combination with methotrexate (MTX) for reducing signs and symptoms in adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more anti-TNF-alpha therapy.

Widely used off-label to treat difficult cases of multiple sclerosis, systemic lupus erythematosus, chronic inflammatory demyelinating polyneuropathy and autoimmune anemias.

Other autoimmune diseases that have been treated with rituximab include autoimmune hemolytic anemia, pure red cell aplasia, thrombotic thrombocytopenic purpura (TTP), idiopathic thrombocytopenic purpura (ITP), Evans syndrome,vasculitis, bullous skin disorders, type 1 diabetes mellitus, Sjogren’s syndrome, anti-NMDA receptor encephalitis and Devic’s disease, Graves’ ophthalmopathy, autoimmune pancreatitis, Opsoclonus myoclonus syndrome, and IgG4-related disease.

It is ineffective in treating IgA-mediated autoimmune diseases. Resistance can be host or lymphoma related.

Mechanisms of resistance is dependent on the patient specific microenvironment of the lymphoma.

It enters lymph nodes and its environs and afects malignant B cells, stromal cells, benign lymphocytes, extracellular matrix,vasculature proteins in th extravascular fluid, cytokines and chemokines.

Eliminates most circulating B cells with recovery of B cell counts in 6-12 months after treatment.

Cells that remain after treatment have a higher surface expression complement inhibitor CD59.

Average duration of response depending upon the subtype of lymphoma is about 1 year.

Most commonly used with CHOP chemotherapy for diffuse large B-cell lymphoma.

The addition of rituximab immunotherapy to CHOP chemotherapy has improved overall survival by 10-15%.(Coiffler).

In patients with de novo immune thrombocytopenic purpura, adding rituximab to corticosteroids appears to delay, but not prevent, relapse.

Caucasian patients with relapsed iTTP had significantly longer relapse-free survival (RFS), compared with African American patients.

Rituximab added to corticosteroids, results in 5-year RFS for Caucasian patients with relapsed disease improves dramatically.

In the corticosteroids plus rituximab group, rates of 1-year and 3-year RFS were significantly higher compared with patients who received corticosteroids alone.

There is no difference at five years (0.60 for corticosteroids plus rituximab vs. 0.56 for corticosteroids alone).

African American patients have a higher risk of relapse, compared with Caucasian patients

Among Caucasian patients, the addition of rituximab significantly improved RFS, compared with corticosteroids alone, but no significant difference in African American patients.

Estimated 5-year RFS was about 50% and 40% in African American patients with de novo iTTP and relapsed iTTP, respectively, regardless of treatment with rituximab.

For Caucasian patients with de novo ITP the 5-year RFS was approximately 80%.

Used with additional agents for ITP.

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