Proposed Mechanism of Action

CD20 is an important target for NHL and CLL therapy

  • CD20 is a cell surface antigen, or protein, that is expressed on the surface of most normal and malignant B cells1
  • CD20 is a stable target that is not shed, found freely circulating in plasma, or internalized upon antibody binding2
  • Both NHL and CLL cells express surface CD20—NHL does so to a greater degree3

RITUXAN is an anti-CD20 monoclonal antibody

  • First FDA-approved monoclonal antibody for the treatment of cancer
  • RITUXAN specifically targets and binds tightly to CD201

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This video depicts:

  • An introduction to the proposed mechanism of action for RITUXAN
  • Antibody-dependent cell-mediated cytotoxicity (ADCC)
  • Complement-dependent cytotoxicity (CDC)
  • Apoptosis

RITUXAN induces B-cell destruction through 3 proposed mechanisms

  • These proposed ways include4
    • ADCC: Natural killer cells, T cells, and macrophages are involved in recognizing and killing antibody-labeled target cells, leading to cell lysis
    • CDC: Binding of the antibody recruits complement proteins, which punch holes in the cell membrane, flooding the cell and leading to cell lysis
    • Apoptosis: Binding of the antibody signals the cell to self-destruct
  • All 3 of these proposed mechanisms of action are potentially important contributors to targeted B-cell destruction4
  • NHL=non-Hodgkin’s lymphoma; CLL=chronic lymphocytic leukemia.

ADCC

Chart: ADCC

CDC

Chart: CDC

Apoptosis

Chart: Apoptosis

References:
  1. RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2011.
  2. Reff ME, Carner K, Chambers KS, et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood. 1994;83:435-445.
  3. Yee KWL, O’Brien SM. Chronic lymphocytic leukemia: diagnosis and treatment. Mayo Clin Proc. 2006;81:1105-1129.
  4. Maloney DG, Smith B, Rose A. Rituximab: mechanism of action and resistance. Semin Oncol. 2002;29(suppl 2):2-9.

Indications

RITUXAN® (Rituximab) is indicated for the treatment of patients with:

  • Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent
  • •  Weekly ×4  •  Weekly ×8  •  Bulky disease  •  Retreatment
  • Previously untreated follicular, CD20-positive, B-cell NHL in combination with first-line chemotherapy and, in patients achieving a complete or partial response to RITUXAN in combination with chemotherapy, as single-agent maintenance therapy
  • Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after first-line CVP chemotherapy
  • Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens
  • Previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide (FC)

RITUXAN is not recommended for use in patients with severe, active infections.

Important Safety Information

WARNING: FATAL INFUSION REACTIONS, TUMOR LYSIS SYNDROME (TLS), SEVERE MUCOCUTANEOUS REACTIONS, and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)

Infusion Reactions: RITUXAN administration can result in serious, including fatal, infusion reactions. Deaths within 24 hours of RITUXAN infusion have occurred. Approximately 80% of fatal infusion reactions occurred in association with the first infusion. Carefully monitor patients during infusions. Discontinue RITUXAN infusion and provide medical treatment for Grade 3 or 4 infusion reactions.

Tumor Lysis Syndrome (TLS): Acute renal failure requiring dialysis with instances of fatal outcome can occur in the setting of TLS following treatment of non-Hodgkin's lymphoma (NHL) with RITUXAN monotherapy.

Severe Mucocutaneous Reactions: Severe, including fatal, mucocutaneous reactions can occur in patients receiving RITUXAN.

Progressive Multifocal Leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving RITUXAN.

Warnings and Precautions

RITUXAN has also been associated with other serious and/or fatal adverse reactions. These include

  • hepatitis B reactivation with fulminant hepatitis; hepatic failure resulting in death
  • serious, including fatal, bacterial, fungal, and new or reactivated viral infections
  • cardiovascular events, including serious or life-threatening cardiac arrhythmias
  • severe, including fatal, renal toxicity
  • abdominal pain, bowel obstruction and perforation, in some cases leading to death, can occur in patients receiving RITUXAN in combination with chemotherapy

Additional Important Safety Information

  • The most common adverse reactions of RITUXAN (incidence ≥25%) observed in clinical trials of patients with NHL were infusion reactions, fever, lymphopenia, chills, infection, and asthenia. The incidence of infusion reactions was highest during the first infusion (77%) and decreased with each subsequent infusion. These infusion reactions typically resolved with slowing or interruption of the infusion and with supportive care. The most frequent Grade 3 or 4 adverse reactions observed in NHL were cytopenias, including lymphopenia
  • The most common adverse reactions of RITUXAN (incidence ≥25%) observed in clinical trials of patients with CLL were infusion reactions and neutropenia. Infusion-related adverse reactions occurring during or within 24 hours of the start of infusion included nausea, pyrexia, chills, hypotension, vomiting, and dyspnea
  • Most CLL patients treated with R-FC experienced at least one Grade 3 or 4 adverse reaction. The Grade 3 or 4 adverse reactions observed more frequently with R-FC compared with FC alone were neutropenia, leukopenia, febrile neutropenia, thrombocytopenia, infusion reactions, pancytopenia, hypotension, and hepatitis B
  • In clinical trials, CLL patients 70 years of age or older who received R-FC had more Grade 3 and 4 adverse reactions compared with younger CLL patients who received the same treatment

For additional safety information, please see the full prescribing information, including BOXED WARNINGS and Medication Guide.

Attention Healthcare Provider: Provide Medication Guide to patient prior to RITUXAN infusion.