What is the standard dosing schedule for rituximab (Rituxan) for B‑cell non‑Hodgkin lymphoma and rheumatoid arthritis?

Rituximab Dosing

For B-cell non-Hodgkin lymphoma, administer rituximab 375 mg/m² intravenously once weekly for 4 weeks as monotherapy, or 375 mg/m² given with each cycle of CHOP chemotherapy (6-8 cycles total) for combination therapy. 1 For rheumatoid arthritis, the standard dose is 1000 mg administered intravenously on days 1 and 15. 2

Non-Hodgkin Lymphoma Dosing by Risk Category

Young, Low-Risk Patients (aa-IPI = 0) Without Bulky Disease

• Six cycles of CHOP combined with six doses of rituximab 375 mg/m² given every 21 days 1
• This represents the current standard of care with Level I, Grade A evidence 1

Young Low-Intermediate Risk (aa-IPI = 1) or Bulky Disease

• Either R-CHOP21 × 6 with radiotherapy to sites of previous bulky disease, or the intensified regimen R-ACVBP 1

Young High- and High-Intermediate Risk (aa-IPI ≥ 2)

• Six to eight cycles of CHOP combined with eight doses of rituximab 375 mg/m² given every 21 days 1
• R-CHOP given every 14 days has not demonstrated survival advantage over standard 21-day intervals 1

Patients Aged 60-80 Years

• Six to eight cycles of CHOP plus eight doses of rituximab 375 mg/m² given every 21 days 1
• If R-CHOP is given every 14 days, six cycles of CHOP with eight cycles of rituximab are sufficient 1

Patients Aged >80 Years

• Rituximab 375 mg/m² combined with attenuated chemotherapy (R-miniCHOP) 1

Indolent Non-Hodgkin Lymphoma

• Rituximab 375 mg/m² IV weekly for 4 doses as monotherapy or in combination regimens 3
• For maintenance therapy after initial treatment with high tumor burden: rituximab 375 mg/m² once every 8 weeks for 12 doses 3, 4

Rheumatoid Arthritis Dosing

• 1000 mg administered intravenously on days 1 and 15 2
• This represents the American College of Rheumatology standard dosing protocol 2

B-Cell Acute Lymphoblastic Leukemia (CD20-Positive)

• 375 mg/m² intravenously 1 day before chemotherapy 1
• Eight infusions of rituximab over the course of treatment cycles is the recommended standard 1
• Only include patients with CD20 expression ≥20% of leukemic blast cells 1

ANCA-Associated Vasculitis

Induction Therapy

• 375 mg/m² intravenously once weekly for 4 consecutive weeks 2, 4

Maintenance Therapy (Two Protocol Options)

• MAINRITSAN scheme: 500 mg × 2 at complete remission, then 500 mg at months 6,12, and 18 4
• RITAZAREM scheme: 1000 mg after induction, then at months 4,8,12, and 16 4

Administration Guidelines

Premedication

• Administer antipyretic and antihistamine before infusion to reduce infusion reactions 4
• Infusion reactions occur in up to 77% of patients during first infusion 4

Pre-Treatment Screening (Mandatory)

• Hepatitis B and C screening 2, 4
• Baseline immunoglobulin levels (IgG, IgM, IgA) 2, 4
• Latent tuberculosis screening 2
• Complete blood count with differential 2, 4
• Comprehensive metabolic panel including hepatic and renal function 4

Monitoring During Treatment

• Complete blood count with differential at baseline and at 2-4 month intervals 2, 4
• Immunoglobulin levels before each rituximab course and in patients with recurrent infections 4
• For vasculitis patients: urinalysis at every clinic visit; inflammatory markers (ESR/CRP) and renal function tests every 1-3 months 4

Critical Safety Considerations

Tumor Lysis Syndrome Prevention

• In patients with high tumor load, implement precautions to avoid tumor lysis syndrome 1
• Consider prophylaxis in high-risk patients 2, 3

Infection Prophylaxis

• Pneumocystis jirovecii prophylaxis with trimethoprim-sulfamethoxazole 800 mg/160 mg on alternate days or 400 mg/80 mg daily 4
• Alternative agents include dapsone, atovaquone, or inhaled pentamidine for intolerant patients 4

Hepatitis B Reactivation

• Antiviral prophylaxis or periodic HBV DNA monitoring and antiviral treatment for patients previously exposed to HBV 1
• Fatal hepatitis B reactivation has been reported in rheumatoid arthritis patients 5

Dose Modifications

• Avoid dose reductions due to hematological toxicity whenever possible in patients treated with curative intent 1, 4
• Use prophylactic haematopoietic growth factors in patients >60 years of age 1

Severe Adverse Events to Monitor

• Progressive multifocal leukoencephalopathy (PML) - rare but fatal complication 2, 4
• Severe infusion reactions (bronchospasm, hypotension, cytokine release syndrome) occur in ~10% of patients 4
• Hypogammaglobulinemia develops in 23.3% (IgM), 5.5% (IgG), and 0.5% (IgA) of RA patients with repeated treatment 6
• Fatal sepsis reported in transplant patients 4

Management of Infusion Reactions

• Grade 1/2 reactions: slow or temporarily stop infusion and provide symptomatic treatment 4
• Grade 3/4 reactions: stop infusion and provide aggressive symptomatic treatment 4