• Rituximab (Rituxan, MabThera, Zytux) (see Rituximab, [[Rituximab]])
  • Pharmacology: chimeric monoclonal antibody against B-cell surface CD20, resulting in B-cell depletion (which lasts for several months)
    • Immunoglobulin Levels Remain Normal: in most cases
      • Exception: when rituzimab is used prior to stem cell transplant or as maintenance after stem cell transplant, persistent hypogammaglobulinemia is common
    • Rituximab Use is Associated with Increased Risk of Neutropenia
    • Rituximab May Also Interfere with T-Cell Function: some data exist to support this mechanism
• Ibritumomab Tiuxetan (Zevalin) (see Ibritumomab, [[Ibritumomab]])
  • Pharmacology: radioimmunotherapeutic agent, consisting of murine anti-human CD20 monoclonal antibody conjugated with the chelating agent tiuxetan (which chelates the radioisotopes indium-111 and yttrium-90)
• Obinutuzumab (Gazyva) (see Obinutuzumab, [[Obinutuzumab]])
  • Pharmacology: glycoengineered type II monoclonal antibody against B-cell CD20
• Ocrelizumab (see Ocrelizumab, [[Ocrelizumab]])
  • Pharmacology: humanized (90%-95% human) monoclonal antibody against B-cell surface CD20, resulting in B-cell depletion
• Ofatumumab (Arzerra, HuMax-CD20) (see Ofatumumab, [[Ofatumumab]])
  Pharmacology
  • Pharmacology: fully human monoclonal antibody against B-cell surface CD20, resulting in B-cell depletion

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Pharmacology

• Binding to B-Cell Surface CD20 Receptors, Resulting in Profound B-Cell Depletion

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Adverse Effects

Cardiovascular Adverse Effects

Cardiac Arrest (see Cardiac Arrest, [[Cardiac Arrest]])

• Epidemiology: reported with rituximab

Cytokine Release Syndrome (see Cytokine Release Syndrome, [[Cytokine Release Syndrome]])

• Epidemiology: reported with rituximab

Infectious Adverse Effects

Babesiosis (see Babesiosis, [[Babesiosis]])

• Epidemiology: possibly etiologic, reported with rituximab

Cytomegalovirus (CMV) (see Cytomegalovirus, [[Cytomegalovirus]])

• Epidemiology: possibly etiologic, reported with rituximab

Enterovirus Meningioencephalitis (see Enteroviruses, [[Enteroviruses]])

• Epidemiology: possibly etiologic, reported with rituximab

Hepatitis B Reactivation (see Hepatitis B Virus, [[Hepatitis B Virus]])

• Epidemiology: reported with rituximab and ofatumumab
• Clinical
  • Acute Hepatitis (see Hepatitis, [[Hepatitis]])
  • Fulminant Hepatic Failure (FHF) (see Fulminant Hepatic Failure, [[Fulminant Hepatic Failure]])
• Prevention: recommended to screen patients for hepatitis B prior to rituximab administration

Infection

• Epidemiology: reported with rituximab
  • Generally increased risk
  • In solid organ transplants, the most important risk factor for infection-related death was the concomitant use of rituximab and rabbit ATG
• Mechanism: may be (at least) partly related to hypogammaglobulinemia
  • Trials that used rituximab before/after stem cell transplant demonstrated persistent hypogammaglobulinemia and increased risk of multiple infections (TB, CMV, varicella-zoster, PML, etc) -> some patients required IVIG replacement

Mycobacterium Avium Complex (MAC) (see Mycobacterium Avium Complex, [[Mycobacterium Avium Complex]])

• Epidemiology: possibly etiologic, reported with rituximab

Mycobacterium Kansasii (see Mycobacterium Kansasii, [[Mycobacterium Kansasii]])

• Epidemiology: possibly etiologic, reported with rituximab

Parvovirus B19 with Pure Red Cell Aplasia (see Parvovirus B19, [[Parvovirus B19]])

• Epidemiology: possibly etiologic, reported with rituximab

Pneumocytsis Jirovecii Pneumonia (PCP) (see Pneumocystis Jirovecii, [[Pneumocystis Jirovecii]])

• Epidemiology: possibly etiologic, reported with rituximab

Progressive Multifocal Encephalopathy (PML) (see Progressive Multifocal Leukoencephalopathy, [[Progressive Multifocal Leukoencephalopathy]])

• Epidemiology: reported with rituximab and ofatumumab
• Mechanism: anti-CD20 agents reactivate the latent JC polyoma virus, which has lytic effect on oligodenodrocytes in the brain

West Nile Virus (see Encephalitis, [[Encephalitis]])

• Epidemiology: possibly etiologic, reported with rituximab

Neurologic Adverse Effects

Posterior Reversible Encephalopathy Syndrome (PRES) (see Posterior Reversible Encephalopathy Syndrome, [[Posterior Reversible Encephalopathy Syndrome]])

• Epidemiology: reported with rituximab

Pulmonary Adverse Effects

Cytokine Release Syndrome (see Cytokine Release Syndrome, [[Cytokine Release Syndrome]])

• Epidemiology: reported with rituximab

Cytomegalovirus (CMV) (see Cytomegalovirus, [[Cytomegalovirus]])

• Epidemiology: possibly etiologic, reported with rituximab

Diffuse Alveolar Hemorrhage (DAH) (see Diffuse Alveolar Hemorrhage, [[Diffuse Alveolar Hemorrhage]])

• Epidemiology: case reports with rituximab

Interstitial Lung Disease (ILD) (see Interstitial Lung Disease, [[Interstitial Lung Disease]])

• Epidemiology: rituximab pulmonary toxicity typically develops after a few infusions of the drug and relapses when treatment is resumed
• Diagnosis
  • Bronchoscopy (see Bronchoscopy, [[Bronchoscopy]]): in one patient, CD4+ lymphocytosis was found in the BAL fluid
  • Open Lung Biopsy: in one case, a pattern of Desquamative Interstitial Pneumonia (see Desquamative Interstitial Pneumonia, [[Desquamative Interstitial Pneumonia]]) was found
• Treatment/Prognosis: corticosteroids typically are effective [MEDLINE]

Pneumocytsis Jirovecii Pneumonia (PCP) (see Pneumocystis Jirovecii, [[Pneumocystis Jirovecii]])

• Epidemiology: possibly etiologic, reported with rituximab

Mycobacterium Avium Complex (MAC) (see Mycobacterium Avium Complex, [[Mycobacterium Avium Complex]])

• Epidemiology: possibly etiologic, reported with rituximab

Mycobacterium Kansasii (see Mycobacterium Kansasii, [[Mycobacterium Kansasii]])

• Epidemiology: possibly etiologic, reported with rituximab

Other Adverse Effects

Tumor Lysis Syndrome (see Tumor Lysis Syndrome, [[Tumor Lysis Syndrome]])

• Epidemiology: reported with rituximab

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References

• Fatal Cytokine Release Syndrome With Chimeric Anti-CD20 Monoclonal Antibody Rituximab in a 71-Year-Old Patient With Chronic Lymphocytic Leukemia. JCO June 1, 1999 vol. 17 no. 6 1962-1963
• Desquamative alveolitis: an unusual complication of treatment with Mabthera. Blood 1999;94:271
• Pulmonary complications after autologous transplantation and immunotherapy with rituximab in patients with follicular lymphoma [abstract]. Blood 2000;96:383a
• Interstitial pneumonitis related to rituximab therapy. N Engl J Med 2003;348:2690-2691 [MEDLINE]
• Fatal intra-alveolar hemorrhage after rituximab in a patient with non-Hodgkin lymphoma. Leukemia Lymphoma 2004;45:2321-2325
• Rituximab consolidation after high-dose chemotherapy and autologous blood stem cell transplantation in follicular and mantle cell lymphoma: a prospective, multicenter phase II study. Ann Oncol. 2004;15:1691– 8
• Rituximab-induced acute pulmonary fibrosis. Mayo Clin Proc 2004;79:949-953
• Interstitial pneumonitis following rituximab therapy for immune thrombocytopenic purpura (ITP). Am J Hematol 2004;77:103-104
• A case of interstitial pneumonia induced by rituximab therapy. Int J Hematol 2005;81:169-170
• Hypogammaglobulinemia with a selective delayed recovery in memory B cells and an impaired isotype expression after rituximab administration as an adjuvant to autologous stem cell transplantation for non-Hodgkin lymphoma. Eur J Haematol. 2006;77:226-32
• High incidence of non-neutropenic infections induced by rituximab plus fludarabine and associated with hypogammaglobulinemia: a frequently unrecognized and easily treatable complication. Ann Oncol. 2006;17:1424-7
• B-cell depletion for 2 years after autologous stem cell transplant for NHL induces prolonged hypogammaglobulinemia beyond the rituximab maintenance period. Leuk Lymphoma. 2008;49:152–3
• Rituximab purging and maintenance combined with auto-SCT: long-term molecular remissions and prolonged hypogamma- globulinemia in relapsed follicular lymphoma. Bone Marrow Transplant. 2009;43:701-8
• Seminars in Hematology, Vol 47, No 2, April 2010, pp 187–198
• Incidence of Hypogammaglobulinemia in Patients Receiving Rituximab and the Use of Intravenous Immunoglobulin for Recurrent Infections. Clin Lymphoma Myeloma Leuk. Dec 28 2012 [MEDLINE]
• Rituximab for ANCA-associated vasculitides. Clin Exp Rheumatol. 2014 May-Jun;32(3 Suppl 82):S118-21. Epub 2014 May 16 [MEDLINE]
• Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med. 2014 Nov 6;371(19):1771-80. doi: 10.1056/NEJMoa1404231 [MEDLINE]