What does it mean when a patient comes for Rituximab (rituximab) treatment?

What It Means When a Patient Comes for Rituximab Treatment

Rituximab is a chimeric monoclonal antibody targeting CD20-positive B-cells, used to treat various B-cell malignancies (particularly non-Hodgkin's lymphoma) and autoimmune conditions (including rheumatoid arthritis, ANCA-associated vasculitis, and pemphigus vulgaris). 1

Primary Indications

The patient is most likely receiving rituximab for one of these conditions:

Hematologic Malignancies

• Non-Hodgkin's Lymphoma (NHL): Most common indication, including follicular lymphoma, diffuse large B-cell lymphoma, and other CD20-positive B-cell lymphomas 2, 3
• Waldenström's Macroglobulinemia: Used as monotherapy or in combination with chemotherapy 2
• Chronic Lymphocytic Leukemia: Though less commonly than NHL 3

Autoimmune Conditions

• ANCA-Associated Vasculitis: Including granulomatosis with polyangiitis (Wegener's) and microscopic polyangiitis 2
• Rheumatoid Arthritis: Particularly in patients who have failed TNF antagonists 1
• Pemphigus Vulgaris and other autoimmune blistering diseases 4

Mechanism and Expected Effects

Rituximab depletes B-cells through complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity, resulting in near-complete peripheral B-cell depletion within 2 weeks. 1

• B-cell depletion persists for 6-12 months in most patients, with recovery beginning around 6 months and median levels returning to normal by 12 months 4, 1
• CD20 is not expressed on stem cells, allowing eventual B-cell recovery 3

Standard Dosing Regimens

The specific regimen depends on the indication:

For Non-Hodgkin's Lymphoma

• Standard schedule: 375 mg/m² IV once weekly for 4 weeks 2, 4
• Overall response rates: 30-60% with duration of response 8-11 months 2
• Extended schedule: Additional 4 weekly infusions at weeks 12-16 for responders, achieving duration of response 16-29 months 2

For Rheumatoid Arthritis

• 1000 mg IV on day 0, repeated on day 15 4
• Maintenance: 1000 mg IV every 24 weeks based on clinical response 4

For ANCA-Associated Vasculitis

• 375 mg/m² IV once weekly for 4 weeks as induction therapy, combined with glucocorticoids 2

Critical Pre-Treatment Requirements

Before initiating rituximab, specific screening and monitoring must be performed:

Mandatory Screening 4, 1

• Hepatitis B and C antibodies, including occult hepatitis B infection (HBV reactivation can cause fulminant liver failure and death) 5, 1
• Baseline immunoglobulin levels (IgG, IgM, IgA) 4
• Complete blood count 4

Pre-Medication 5

• Antihistamines and acetaminophen 30 minutes before infusion to reduce infusion-related reactions 5
• Consider corticosteroids for high-risk patients 5

Expected Adverse Effects and Management

Infusion-Related Reactions (Most Common)

• Occur in 50-87% of patients during first infusion, decreasing markedly with subsequent doses 3, 6
• Mild to moderate: Fever, chills, rigors, myalgia, headache, rash, urticaria 5, 6
• Severe reactions in ~10%: Bronchospasm, hypotension, hypoxia, pulmonary infiltrates 5, 3
• Fatal reactions are rare but characterized by respiratory distress, myocardial infarction, ventricular fibrillation, cardiogenic shock 5

Infectious Complications

• Hepatitis B reactivation: Potentially fatal; requires screening and preemptive antiviral therapy if positive 5
• Progressive multifocal leukoencephalopathy (PML): Rare but lethal JC virus encephalitis 5
• Pneumocystis pneumonia: Increased risk, particularly with concomitant immunosuppression; prophylaxis should be considered 2
• Late-onset neutropenia: Can occur, especially when combined with chemotherapy 2

Immunologic Effects

• Hypogammaglobulinemia: Risk increases with multiple courses; IgM most affected 1
• Monitor IgG levels every 6 months; low baseline IgG (<3 g/L) predicts greater risk of secondary immunodeficiency 2
• Antibody responses to vaccines dramatically reduced for median 9 months (range 5.9-14.4 months) 5

Special Considerations for Specific Conditions

Waldenström's Macroglobulinemia

• IgM flare occurs in ~50% of patients during first months of treatment 2
• Not associated with treatment failure, but can cause hyperviscosity complications 2
• Patients with IgM ≥4000 mg/dL should undergo prophylactic plasmapheresis or avoid rituximab until IgM decreases 2

ANCA-Associated Vasculitis with Severe Kidney Disease

• Limited data for rituximab alone when serum creatinine >4 mg/dL (>354 μmol/L) 2
• Consider combining rituximab with cyclophosphamide: 4 weekly rituximab infusions plus 2 IV cyclophosphamide pulses 2

Ongoing Monitoring Requirements

During treatment, monitor: 4, 5

• Complete blood count at 2-4 month intervals for cytopenias 4
• Immunoglobulin levels every 6 months 2, 4
• Cardiac monitoring during and after infusions for patients with arrhythmia history or angina 1
• Signs of infection, particularly opportunistic infections 5

Common Pitfalls to Avoid

• Do not interpret IgM flare as treatment failure in Waldenström's macroglobulinemia 2
• Do not stop ibrutinib abruptly if patient is on concurrent therapy; increases in IgM and hemoglobin reductions can occur 2
• Do not administer live vaccines before or during treatment; non-live vaccines should be given at least 4 weeks prior to rituximab 1
• Do not overlook hepatitis B screening; reactivation is potentially fatal 5, 1
• Recognize that elderly patients may be at higher risk for serious adverse reactions including infections, neutropenia, and pancytopenia 4