II. Indications: Leukemia and Lymphoma

  1. Non-Hodgkin's Lymphoma
    1. Rituximab
    2. Ibritumomab tiuxetan
    3. Tositumomab-Iodine 131
  2. Large B cell Lymphoma
    1. Rituximab
  3. Burkitt Lymphoma
    1. Rituximab
  4. Follicular Lymphoma
    1. Obinutuzumab
  5. Chronic Lymphocytic Leukemia
    1. Rituximab
    2. Ofatumumab
  6. Acute Mature B Cell Leukemia
    1. Rituximab

IV. Contraindications

  1. Active Hepatitis BVirus Infection
    1. Screen before starting regimen

V. Mechanism

  1. See Monoclonal Antibody-Mediated Chemotherapy
  2. CD20 Antigens
    1. CD20 Antigens are phosphoproteins found only on the surface of B-Cells including Leukemia, Lymphoma (but not B-Cell precursors)
    2. Regulate transmembrane Calcium conductance
    3. Plays a role in B-Cell Activation and proliferation, as well as complement-dependent cytotoxicity
  3. Anti-CD20 Monoclonal Antibody
    1. Recombinant human Monoclonal Antibody directed against the CD20 Antigen cell surface marker
    2. Bind CD20 and triggers a cytotoxic immune response, depleting CD20 positive B Cells

VI. Medications: Anti-CD20

  1. Rituximab (Rituxan)
    1. See Rituximab
    2. Used in Non-Hodgkin's Lymphoma (as well as several other Lymphomas and Leukemias)
    3. Also used in Refractory Rheumatoid Arthritis, Granulomatosis with Polyangiitis
    4. Risk of severe infusion reactions and severe mucocutaneous reactions
    5. Also risk of PML, Tumor Lysis Syndrome, Hepatitis B reactivation and Bowel Obstruction and perforation
    6. Also risk of Acute Kidney Injury, Cardiac Arrhythmia and severe cytopenia
  2. Ofatumumab (Arzerra, Kesimpta)
    1. Used in Chronic Lymphocytic Leukemia (Arzerra) and Multiple Sclerosis (Kesimpta)
    2. Risk of severe infusion reactions, Severe infections, Hepatitis B reactivation
  3. Obinutuzumab (Gazyva)
    1. Used in CLL, Follicular Lymphoma
    2. Risk of Hepatitis B reactivation, PML, DIC, Tumor Lysis Syndrome, infusion reactions, severe infections, cytopenias,
  4. Ocrelizumab (Ocrevus)
    1. Indicated for Multiple Sclerosis (relapsing, and primary progressive)
      1. First-line only in primary progresive MS (only one FDA approved in primary progressive MS)
    2. Pretreat doses with Methylprednisolone and Diphenhydramine (or other Antihistamine) 30 to 60 minutes before dose
    3. Adults with MS
      1. Load: 300 mg IV infusion over 3.5 hours for 2 doses, 2 weeks apart
      2. Maintenance: 600 mg IV infusion over 3.5 hours every 6 months

VII. Medications: Anti-CD20 with Cytotoxic Conjugates

  1. Ibritumomab tiuxetan (Zevalin)
    1. Used for Non-Hodgkin's Lymphoma
    2. Risk of severe infusion reactions, cytopenias and secondary malignancies
    3. Conjugate of CD20 Monoclonal Antibody (Ibritumomab) and a radioisotope chelation site (tiuxetan)
      1. Tiuxetan is bound to Iridium-111 or yttrium Y-90
      2. Delivers cytotoxic dose of radiation to B Cells with CD20 cell surface marker
  2. Tositumomab-Iodine 131 (Bexxar)
    1. Used for Non-Hodgkin's Lymphoma
    2. Risk of severe infusion reactions, cytopenia, secondary malignancy, Hypothyroidism
    3. Conjugate of CD20 Monoclonal Antibody (Tositumomab) and a radioisotope, Iodine-131
      1. Delivers cytotoxic dose of radiation to B Cells with CD20 cell surface marker

VIII. Dosing

  1. See other references for disease specific dosing protocols

IX. Adverse Effects

  1. Severe infusion reactions including Anaphylaxis (Rituximab, Ofatumumab, Ibritumomab, Obinutuzumab, Tositumomab)
  2. Severe mucocutaneous syndrome (Rituximab, Ibritumomab)
  3. Progressive Multifocal Leukoencephalopathy (Rituximab, Ofatumumab, Obinutuzumab)
  4. Tumor Lysis Syndrome (Rituximab, Obinutuzumab)
  5. Hepatitis B reactivation (Rituximab, Ofatumumab, Obinutuzumab)
  6. Acute Kidney Injury (Rituximab)
  7. Cardiac Arrhythmia (Rituximab)
  8. Severe cytopenia (Rituximab, Ofatumumab, Ibritumomab, Obinutuzumab, Tositumomab)
  9. Bowel Obstruction and perforation (Rituximab, Ofatumumab)
  10. Severe infections (Rituximab, Obinutuzumab)
  11. Hypothyroidism (Tositumomab-I131)
  12. Secondary malignancy (Ibritumomab-tiuxetan, Tositumomab-I131)
    1. Acute Myelogenous Leukemia
    2. Myelodysplastic Syndrome

X. Safety

  1. Avoid in Lactation
  2. Avoid in pregnancy (all trimesters, Pregnancy category X)
    1. Use reliable Contraception

XI. Drug Interactions

  1. Vaccines
    1. Give non-Live Vaccines at least 2 weeks prior to dosing
    2. Hold CD20 Monoclonal Antibody for 6 months before and 4-6 weeks after Live Vaccines
      1. Ideally, give Live Attenuated Vaccines at least 6 weeks before starting CD20 Monoclonal Antibodies

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Related Studies

Ontology: CD20 Antigens (C0054946)

Definition (NCI) B-lymphocyte antigen CD20 (297 aa, ~33 kDa) is encoded by the human MS4A1 gene. This protein plays a role in both the activation and proliferation of B-cells.
Definition (MSH) Unglycosylated phosphoproteins expressed only on B-cells. They are regulators of transmembrane Ca2+ conductance and thought to play a role in B-cell activation and proliferation.
Concepts Amino Acid, Peptide, or Protein (T116) , Immunologic Factor (T129)
MSH D018951
SnomedCT 82753007
LNC LP14623-0, LP37559-9, MTHU001655, MTHU022267
English Antigen, CD20, Antigens, CD20, CD20 Antigen, CD20 - Cluster of diff ag 20, Cluster of diff antigen 20, HRF-20 - Human restric fact 20, ANTIGENS CD 020, CD 020 ANTIGENS, B-Lymphocyte Antigen CD20, Antigens, CD20 [Chemical/Ingredient], cd20 antigen, CD20 Ag, CD20, Lymphocyte antigen CD20, CD20 - Cluster of differentiation antigen 20, Cluster of differentiation antigen 20, HRF-20 - Human restriction factor 20, Human restriction factor 20, Leucocyte 16, Leukocyte 16, Lymphocyte antigen CD20 (substance), B1, Bp35, B-Lymphocyte Surface Antigen B1, CD20 Receptor, Leu-16, MS4A1, Membrane-Spanning 4-Domains Subfamily A Member 1, CD20 Antigens
Swedish CD20-antigener
Czech antigeny CD20
Finnish CD20-antigeenit
Russian ANTIGENY CD20, CD20 ANTIGENY, CD20 АНТИГЕНЫ, АНТИГЕНЫ CD20
Japanese CD20抗原, 抗原-CD20
French Antigènes CD20, Antigène CD20, CD20
German ANTIGENE CD 020, CD 020 ANTIGENE, Antigene, CD20-, CD20-Antigene
Polish Antygeny CD20
Croatian Antigeni, CD20
Spanish antígeno linfocitario CD20 (sustancia), antígeno linfocitario CD20, Antígenos CD20
Italian Antigeni CD20
Portuguese Antígenos CD20

Ontology: iodine-131-tositumomab (C0768182)

Definition (NCI_NCI-GLOSS) A monoclonal antibody (tositumomab) that has been chemically changed by adding radioactive iodine, and that is used in the treatment of certain types of non-Hodgkin lymphoma. It belongs to the family of drugs called radioconjugated monoclonal antibodies. When iodine I 131 tositumomab and tositumomab are given together, the combination is called the Bexxar regimen.
Definition (NCI) A monoclonal antibody directed against the CD20 protein expressed on the surface of B-lymphocytes and radiolabeled with the radioisotope iodine I 131 with potential antineoplastic activity. Iodine I 131 tositumomab binds to and selectively delivers cyctotoxic radiation to CD20-expressing B-lymphocytes, thereby minimizing systemic radiotoxicity.
Definition (PDQ) A monoclonal antibody directed against a protein (CD20) expressed on the surface of B-lymphocytes and radiolabeled with the radioisotope I 131 with potential antineoplastic activity. Iodine I 131 tositumomab delivers radiation selectively to neoplastic CD20-expressing B-lymphocytes cells, thereby decreasing the risk of systemic radiotoxicity. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42806&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42806&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C2444" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Immunologic Factor (T129) , Amino Acid, Peptide, or Protein (T116)
MSH C119496
English I 131 Monoclonal Antibody Anti-B1, I 131 Tositumomab, Iodine I 131 Tositumomab, Iodine-131 Tositumomab, 131-I-Anti-B1 Monoclonal Antibody, Iodine-131 Anti-CD20 Monoclonal Antibody, 131-I-Anti-B1 Antibody, Iodine-131 Anti-B1 Antibody, I-131 anti-B1 antibody, iodine-131 anti-B1 antibody, iodine-131 anti-B1 monoclonal antibody, iodine-131-labeled anti-CD20 antibody, 131I anti-B1, TOSITUMOMAB I-131, iodine-131 anti-B1 antibody [Chemical/Ingredient], tositumomab iodine i 131, iodine i 131 tositumomab, anti-b1, iodine-131 tositumomab, tositumomab iodine-131, tositumomab/iodine (131I) tositumomab, chemotherapeutics tositumomab + iodine-131, tositumomab + iodine-131, tositumomab + iodine-131 (medication), iodine-131-tositumomab, iodine I 131 monoclonal antibody anti-B1, iodine I 131 MOAB anti-B1, iodine I 131 tositumomab, I131-MOAB-B1, Iodine I 131 MOAB Anti-B1, Iodine I 131 Monoclonal Antibody Anti-B1, TOSITUMOMAB IODINE-131

Ontology: ibritumomab tiuxetan (C0877880)

Definition (NCI) An immunoconjugate of the monoclonal antibody ibritumomab conjugated with the linker-chelator tiuxetan, a high affinity, conformationally restricted chelation site for radioisotopes. When bound to indium In 111 or yttrium Y 90, ibritumomab tiuxetan, targeting the CD20 antigen on B cell surfaces, specifically delivers a potentially cytotoxic dose of radiation to B lymphocytes. Ibritumomab is a murine IgG1 kappa monoclonal antibody directed against the CD20 antigen, which is found on the surface of normal and malignant B lymphocytes.
Definition (NCI) A murine monoclonal antibody directed against the CD20 phosphoprotein, expressed on the cell surface of normal B-lymphocytes and B-cell lymphomas.
Definition (NCI_NCI-GLOSS) A monoclonal antibody that is used to treat certain types of B-cell non-Hodgkin lymphoma and is being studied in the treatment and detection of other types of B-cell tumors. Monoclonal antibodies are made in the laboratory and can locate and bind to substances in the body, including cancer cells. Ibritumomab binds to the protein called CD20, which is found on B cells. It is linked to the compound tiuxetan. This allows certain radioisotopes to be attached before it is given to a patient. It is a type of monoclonal antibody-chelator conjugate.
Concepts Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116) , Immunologic Factor (T129)
MSH C422802
SnomedCT 410951004, 385548008
English Ibritumomab Tiuxetan, IDEC-129, IBRITUMOMAB TIUXETAN, ibritumomab tiuxetan [Chemical/Ingredient], ibritumomab tiuxetan, Ibritumomab tiuxetan (product), Ibritumomab tiuxetan, Ibritumomab tiuxetan (substance), IDEC-2B8, Murine Monoclonal Antibody 2B8
Spanish ibritumomab tiuxetano (producto), ibritumomab tiuxetano (sustancia), ibritumomab tiuxetano

Ontology: tositumomab (C0879399)

Definition (NCI_NCI-GLOSS) A monoclonal antibody that is used in the treatment of certain types of non-Hodgkin lymphoma. When tositumomab and iodine I 131 tositumomab (a form of tositumomab that has been chemically changed by adding radioactive iodine) are given together, the combination is called the Bexxar regimen.
Definition (NCI) A murine IgG2 monoclonal antibody directed against the CD20 antigen, found on the surface of B-cells. Tositumomab binds to the CD20 surface membrane antigen, resulting in apoptosis, and may stimulate antitumoral cell-mediated and/or antibody-dependent cytotoxicity. (NCI04)
Definition (PDQ) A murine IgG2 monoclonal antibody directed against the CD20 antigen, found on the surface of B-cells. Tositumomab binds to the CD20 surface membrane antigen, resulting in apoptosis, and may stimulate antitumoral cell-mediated and/or antibody-dependent cytotoxicity. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=37818&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=37818&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C2543" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Immunologic Factor (T129) , Amino Acid, Peptide, or Protein (T116)
SnomedCT 404835009, 407318006
English monoclonal antibody anti-B1, Anti-CD20 Antibody, anti-B1, TOSITUMOMAB, anti-b1, chemotherapeutics tositumomab, tositumomab (medication), tositumomab, Tositumomab (product), Tositumomab (substance), Tositumomab, anti-B1 monoclonal antibody, MOAB anti-B1, MoAb Anti-B1, Monoclonal Antibody Anti-B1
Spanish tositumomab (producto), tositumomab (sustancia), tositumomab

Ontology: Ibritumomab (C1272713)

Concepts Amino Acid, Peptide, or Protein (T116) , Immunologic Factor (T129)
SnomedCT 385546007
English Ibritumomab (product), Ibritumomab, ibritumomab
Spanish ibritumomab (producto), ibritumomab

Ontology: ofatumumab (C1832027)

Definition (NCI) A fully human, high-affinity IgG1 monoclonal antibody directed against the B cell CD20 cell surface antigen with potential antineoplastic activity. Ofatumumab binds specifically to CD20 on the surfaces of B cells, triggering complement-dependent cell lysis (CDCL) and antibody-dependent cell-mediated cytotoxicity (ADCC) of B cells overexpressing CD20. The CD20 antigen, found on over 90% of B cells, B cell lymphomas, and other B cells of lymphoid tumors of B cell origin, is a non-glycosylated cell surface phosphoprotein that acts a calcium ion channel; it is exclusively expressed on B cells during most stages of B cell development.
Definition (NCI_NCI-GLOSS) A drug used to treat chronic lymphocytic leukemia (CLL) that has not gotten better with other chemotherapy. It is also being studied in the treatment of other types of cancer, including follicular non-Hodgkin lymphoma. Arzerra binds to CD20, a protein on the surface of normal B cells and most B-cell tumors. This may kill the cancer cells. It is a type of monoclonal antibody.
Concepts Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116) , Immunologic Factor (T129)
MSH C527517
SnomedCT 444607009, 444609007
English ofatumumab, OFATUMUMAB, Ofatumumab, Ofatumumab (product), Ofatumumab (substance)
Spanish ofatumumab (sustancia), ofatumumab, ofatumumab (producto)

Ontology: obinutuzumab (C2742503)

Definition (NCI) A glycoengineered, humanized IgG1 monoclonal antibody with potential antineoplastic activity. Afutuzumab, a third generation type II anti-CD20 antibody, selectivity binds to the extracellular domain of the human CD20 antigen on malignant human B cells. The Fc region carbohydrates of the antibody, enriched in bisected non-fucosylated glycosylation variants, contribute to its higher binding affinity for human FcgammaRIII receptors compared to non-glycoengineered antibodies, resulting in enhanced antibody-dependent cellular cytotoxicity (ADCC) and caspase-independent apoptosis. In addition, modification of elbow hinge sequences within the antibody variable framework regions may account for the strong apoptosis-inducing activity of R7159 upon binding to CD20 on target cells.
Concepts Amino Acid, Peptide, or Protein (T116) , Immunologic Factor (T129) , Pharmacologic Substance (T121)
MSH C543332
English huMAB(CD20), Afutuzumab, Obinutuzumab, obinutuzumab, OBINUTUZUMAB, Immunoglobulin G1, anti-(human CD20 (antigen)) (human-mouse monoclonal GA101 heavy chain), disulfide with human-mouse monoclonal GA101 KAPPA-chain, dimer, afutuzumab