What are the uses and dosages of Rituximab?

Rituximab: Uses and Dosages

Rituximab is primarily used for treating non-Hodgkin's lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, and ANCA-associated vasculitis, with the standard dosage being 375 mg/m² administered intravenously once weekly for 4 weeks for most indications. 1

Oncology Indications

Non-Hodgkin's Lymphoma (NHL)

• First-line therapy options (Category 1 evidence): 2

  • Bendamustine + rituximab
  • RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)
  • RCVP (rituximab, cyclophosphamide, vincristine, prednisone)
  • Rituximab monotherapy: 375 mg/m² weekly for 4 doses

• For elderly or infirm patients:

  • Rituximab (preferred): 375 mg/m² weekly for 4 doses
  • Single-agent alkylators (e.g., chlorambucil or cyclophosphamide) ± rituximab

• Maintenance therapy options:

  • High tumor burden: 375 mg/m² one dose every 8 weeks for 12 doses (Category 1) 2, 1
  • After single-agent rituximab: 375 mg/m² one dose every 8 weeks for 4 doses
  • Second-line maintenance: 375 mg/m² one dose every 12 weeks for 2 years (Category 1)

Chronic Lymphocytic Leukemia (CLL)

• Rituximab in combination with fludarabine-based chemotherapy or chlorambucil has shown improved progression-free survival and overall survival 3

Rheumatology Indications

Rheumatoid Arthritis (RA)

• Standard autoimmune protocol: 1
  • 375 mg/m² weekly for 4 weeks OR
  • Two 1000 mg doses given 2 weeks apart

ANCA-Associated Vasculitis (GPA/MPA)

• Induction therapy: 375 mg/m² weekly for 4 weeks 4
• Maintenance therapy: 500 mg every 6 months (FDA-approved) 2
  • Alternative regimens: 1000 mg every 4 months or 1000 mg every 6 months

Hematology Indications

Steroid-Refractory Chronic Graft-Versus-Host Disease (cGVHD)

• Standard dosing: 375 mg/m² once per week for 4-8 infusions 2
• Alternative dosing: 50 mg/m² per week for 4 weeks

Important Monitoring and Precautions

Pre-treatment Screening

• Hepatitis B screening (HBsAg, Anti-HBc)
• Tuberculosis screening
• Baseline complete blood count
• Immunoglobulin levels (IgG, IgM, IgA) 1

Common Adverse Effects

1. Infusion reactions:

   • Occur in approximately 25% of patients with first infusion
   • Usually mild to moderate flu-like symptoms
   • Decrease in frequency with subsequent infusions 5
   • Severe reactions (bronchospasm, hypotension) in approximately 10% of patients

2. Immunosuppression:

   • B-cell depletion typically lasting about 6 months
   • Recovery of B lymphocytes usually seen 9-12 months after therapy 5
   • Hypogammaglobulinemia with repeated treatments 6

Serious Adverse Events to Monitor

• Progressive multifocal leukoencephalopathy (rare but fatal) 6
• Reactivation of hepatitis B virus 6
• Serious infections (but not significantly increased compared to placebo in RA trials) 6

Clinical Pearls

• Seropositivity, complete B-cell depletion shortly after treatment, and previous failure to no more than one anti-TNF agent are associated with better response in RA 6
• Rituximab has demonstrated improved overall response rate, response duration, and progression-free survival when added to combination chemotherapy for NHL 2
• For high tumor burden patients, maintenance therapy significantly improves outcomes 2, 1
• Rituximab is particularly effective for skin manifestations in cGVHD (60% response rate) compared to other organ involvement 2

Dosing Algorithm

1. For lymphoma: Start with 375 mg/m² weekly for 4 doses, then assess response
2. For maintenance in lymphoma: Use appropriate schedule based on disease burden and prior treatment
3. For autoimmune conditions: Choose between weekly protocol (375 mg/m² × 4) or two-dose protocol (1000 mg × 2)
4. For vasculitis maintenance: 500 mg every 6 months is FDA-approved, but alternative regimens may be considered

Always consider patient-specific factors including renal function, hepatic function, and prior treatment history when selecting the appropriate rituximab regimen.