CD20 Monoclonal Antibody

Aka: CD20 Monoclonal Antibody, CD20 Antigen, Ibritumomab, Ibritumomab tiuxetan, Zevalin, Tositumomab, Tositumomab-Iodine-131, Bexxar, Ofatumumab, Arzerra, Kesimpta, Obinutuzumab, Gazyva, Ocrelizumab, Ocrevus

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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

III. Indications: Non-Oncology

  1. Refractory Rheumatoid Arthritis
    1. Rituximab
  2. Granulomatosis with Polyangiitis (formerly known as Wegener's Granulomatosis)
    1. Rituximab
  3. Multiple Sclerosis
    1. Ofatumumab
    2. Ocrelizumab (Ocrevus)
    3. Delgado (2024) J Neurol 271(4):1515-35 +PMID: 37906325 [PubMed]

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

XII. Resources

  1. Rituximab (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b172773b-3905-4a1c-ad95-bab4b6126563
  2. Ibritumomab tiuxetan (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=25d367dc-da65-44c9-a844-1bf15339c285
  3. Tositumomab-Iodine 131 (DailyMed)
    1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/125011s102lbl.pdf
  4. Ofatumumab (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6a8a3f53-2062-48ff-9dbe-b939df133ca3
  5. Obinutuzumab (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=df12ceb2-5b4b-4ab5-a317-2a36bf2a3cda
  6. Ocrelizumab (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9da42362-3bb5-4b83-b4bb-b59fd4e55f0d

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