Rituximab (Rituxan)

CD20-Targeted Antibody for Lymphoma and Leukemia

What is Rituximab? Rituximab (brand name Rituxan) is a monoclonal antibody that targets CD20, a protein found on the surface of B-cells (a type of white blood cell). It's used to treat B-cell lymphomas (including non-Hodgkin lymphoma) and chronic lymphocytic leukemia (CLL). Rituximab revolutionized lymphoma treatment when it was introduced - adding it to chemotherapy dramatically improved cure rates. It works by marking cancer cells for destruction by the immune system and can also kill cells directly.
Drug Class
Anti-CD20 Antibody
Target
CD20 on B-cells
Route
IV Infusion
FDA Approved
1997

How Rituximab Works

Rituximab represents a major advance in cancer treatment - using the body's immune system to fight cancer:

Understanding CD20

Triple Mechanism of Action

How Rituximab Kills Cancer Cells:
  1. Antibody-Dependent Cellular Cytotoxicity (ADCC):
    • Rituximab binds to CD20 on cancer cell surface
    • The antibody "tail" (Fc region) recruits immune cells (NK cells, macrophages)
    • These immune cells recognize the antibody tag and kill the marked cell
    • Think of it like putting a "wanted" poster on cancer cells
  2. Complement-Dependent Cytotoxicity (CDC):
    • Rituximab binding activates the complement system (proteins in blood that help fight infection)
    • Complement proteins form a "membrane attack complex"
    • This punches holes in the cancer cell membrane → cell death
  3. Direct Apoptosis (Cell Suicide):
    • CD20 binding can directly trigger programmed cell death
    • Less well understood mechanism but contributes to overall effect

Synergy with Chemotherapy

Rituximab works even better when combined with chemotherapy:

What is Rituximab Used For?

FDA-Approved Oncology Uses

Non-Hodgkin Lymphoma (NHL)

Chronic Lymphocytic Leukemia (CLL)

Non-Oncology Uses

How is Rituximab Given?

Premedication - REQUIRED!

Mandatory Premedication Before EVERY Infusion:

Given 30-60 minutes before rituximab to prevent infusion reactions:

  • Acetaminophen (Tylenol): 650-1000 mg orally
  • Diphenhydramine (Benadryl): 50 mg IV or orally (antihistamine)
  • Sometimes added:
    • Corticosteroid (prednisone or methylprednisolone) for high tumor burden
    • Additional antihistamine (H2-blocker like famotidine)

Never skip premedication - it significantly reduces infusion reaction risk.

Standard Dosing

R-CHOP Regimen for DLBCL

21-Day Cycle (Day 1 of each cycle):
  • Rituximab: 375 mg/m² IV day 1
  • Cyclophosphamide: 750 mg/m² IV day 1
  • Doxorubicin (Hydroxydaunorubicin): 50 mg/m² IV day 1
  • Vincristine (Oncovin): 1.4 mg/m² IV day 1 (max 2 mg)
  • Prednisone: 100 mg orally days 1-5
  • Total cycles: Usually 6 cycles (some patients 8)
  • Duration: ~4-5 months total

Follicular Lymphoma

Chronic Lymphocytic Leukemia

Infusion Administration

First Infusion (Most Critical):
  • Start SLOW: Begin at 50 mg/hour
  • Gradual increase: If no reaction, increase by 50 mg/hour every 30 minutes
  • Maximum rate: 400 mg/hour
  • Total time: Usually 4-6 hours for first dose
  • Close monitoring: Vital signs every 15-30 minutes; nurse at bedside
Subsequent Infusions (if first dose tolerated):
  • Start at: 100 mg/hour
  • Increase: By 100 mg/hour every 30 minutes if tolerated
  • Maximum: 400 mg/hour
  • Total time: Often 2-4 hours
  • Faster options available: Some patients can receive 90-minute infusion after first cycle

Subcutaneous Formulation

Side Effects and Management

BLACK BOX WARNINGS - Serious and Potentially Fatal Reactions:
  1. Infusion reactions: Can be severe or fatal, especially with first infusion
  2. Tumor lysis syndrome: Massive cell death releases chemicals into blood
  3. Severe mucocutaneous reactions: Skin reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis
  4. Progressive multifocal leukoencephalopathy (PML): Rare fatal brain infection
  5. Hepatitis B reactivation: Can cause fulminant hepatitis, liver failure, death

1. Infusion Reactions - MOST COMMON, ESPECIALLY FIRST DOSE

Incidence and Timing:
  • First infusion: 50-80% experience some reaction (usually mild-moderate)
  • Subsequent infusions: <10% (much lower)
  • Timing: Usually within first 30-120 minutes of infusion, especially first infusion
  • Severity: Most are mild-moderate (grade 1-2); severe reactions in ~10% of first infusions
Symptoms (Cytokine Release Syndrome):
  • Fever, chills, rigors (shaking)
  • Flushing, rash, itching
  • Nausea, headache
  • Throat tightness, cough
  • Dizziness, lightheadedness
  • Severe reactions: Shortness of breath, wheezing, chest tightness, severe hypotension, angioedema
Management:
  • Mild-moderate: Pause infusion, give additional antihistamines, acetaminophen, fluids. Resume at slower rate
  • Severe: Stop infusion immediately. Give epinephrine, corticosteroids, oxygen, IV fluids. May require ICU
  • Prevention: Premedication, slow initial infusion rate, close monitoring

2. Tumor Lysis Syndrome (TLS)

Life-Threatening Emergency - Most Common in CLL and High Tumor Burden:
  • What it is: Rapid destruction of cancer cells releases contents into bloodstream
  • Results: High potassium, high phosphate, high uric acid, low calcium → kidney failure, cardiac arrhythmias, seizures
  • Highest risk:
    • CLL with high white blood cell count (>25,000)
    • Bulky lymphoma (large tumor masses)
    • First dose of rituximab
  • Prevention:
    • Aggressive IV hydration before and during treatment
    • Allopurinol or rasburicase (lowers uric acid)
    • Frequent lab monitoring (every 4-6 hours for high-risk patients)
    • Sometimes hospitalization for first dose
  • Symptoms: Nausea, vomiting, diarrhea, lethargy, muscle cramps, decreased urination, confusion, seizures, irregular heartbeat

3. Immunosuppression and Infections

4. Hepatitis B Virus (HBV) Reactivation

Can Be Fatal - Screening Mandatory Before Starting:
  • Risk: Patients with current or past HBV infection can have virus reactivate → fulminant hepatitis, liver failure, death
  • Required screening: HBsAg and anti-HBc testing BEFORE starting rituximab
  • If positive:
    • Consult hepatology
    • Start antiviral prophylaxis (entecavir or tenofovir) BEFORE rituximab
    • Continue antivirals during treatment and for 12+ months after
    • Monitor liver function tests and HBV DNA levels
  • Symptoms of reactivation: Fatigue, jaundice (yellowing), dark urine, abdominal pain, nausea

5. Progressive Multifocal Leukoencephalopathy (PML)

6. Cardiac Effects

7. Other Side Effects

Rituximab Does NOT Cause:

Monitoring During Treatment

Before Starting Rituximab

Test Purpose Action if Abnormal
HBsAg, anti-HBc Screen for hepatitis B If positive, start antiviral prophylaxis
CBC with differential Baseline blood counts May delay if severe cytopenias
Comprehensive metabolic panel Kidney/liver function, electrolytes Optimize before starting
LDH, uric acid Tumor lysis syndrome risk assessment Prophylaxis if elevated

During Infusion

Between Treatments

How Well Does Rituximab Work?

Diffuse Large B-Cell Lymphoma - Revolutionary Impact

R-CHOP vs. CHOP - Landmark Trials:
  • GELA Study (LNH-98.5):
    • 5-year overall survival: 58% (R-CHOP) vs. 45% (CHOP alone)
    • Event-free survival: 47% vs. 29%
    • Impact: Improved cure rate by ~15-20 percentage points
  • Current outcomes: ~60-70% of DLBCL patients cured with R-CHOP
  • Legacy: R-CHOP became THE standard and has remained so for 20+ years

Follicular Lymphoma

Multiple Proven Benefits:
  • First-line with chemotherapy: Overall response rate 90-95%
  • Maintenance therapy benefit (PRIMA trial):
    • Median PFS: 10.5 years (with rituximab maintenance) vs. 4.1 years (observation)
    • Duration: 2 years of maintenance (every 2 months)
  • Single agent for relapsed disease: Response rate 40-50%

Chronic Lymphocytic Leukemia

Other Lymphomas

How Long is Treatment?

Duration Varies by Disease and Setting

DLBCL (R-CHOP)

Follicular Lymphoma

CLL (FCR)

Single Agent

Drug Interactions and Precautions

Important Considerations

Special Populations

Cost and Insurance Coverage

Medication Cost

Insurance Coverage

Financial Assistance

Biosimilars

FDA-Approved Rituximab Biosimilars:
  • Ruxience (rituximab-pvvr): FDA-approved 2019
  • Truxima (rituximab-abbs): FDA-approved 2018
  • Riabni (rituximab-arrx): FDA-approved 2020
  • What they are: Highly similar to Rituxan with no clinically meaningful differences
  • Same effectiveness and safety: Extensive testing confirms bioequivalence
  • Cost savings: 15-35% less expensive than brand-name Rituxan
  • Interchangeable: Can be substituted; insurance often prefers biosimilars

Frequently Asked Questions

Q: Why do I need premedication before every rituximab infusion?
A: Premedication (Tylenol and Benadryl) dramatically reduces the risk and severity of infusion reactions. Rituximab causes release of cytokines (inflammatory proteins) when it binds to B-cells, especially during the first infusion when there are many B-cells present. This cytokine release causes fever, chills, rigors, and other symptoms in 50-80% of patients during first infusion. Premedication blocks these symptoms. NEVER skip premedication - it's a critical safety measure. Even if you had no reaction to previous doses, continue premedication for every dose.
Q: How long will my first rituximab infusion take?
A: Plan for 5-8 hours total for your first infusion day. This includes: premedication (30-60 min), wait time (30 min), rituximab infusion itself (4-6 hours for first dose - started very slowly and gradually increased), and observation period (30-60 min after). Bring entertainment, snacks, comfortable clothes. Subsequent infusions are usually 2-4 hours once your team knows you tolerate it well. If you're getting other chemotherapy the same day (like CHOP), add another 2-4 hours. It's a long day, but the slow initial rate is important for safety.
Q: I felt terrible during the first infusion - fever, chills, shaking. Is this normal?
A: Yes, unfortunately this is very common with the first rituximab infusion (50-80% of patients experience some reaction). What you're describing sounds like a typical mild-moderate infusion reaction: fever, chills, rigors (shaking), possibly headache, nausea. This happens because massive numbers of B-cells are being killed rapidly, releasing inflammatory proteins (cytokines) into your bloodstream. The good news: subsequent infusions are MUCH better - reactions occur in less than 10% of subsequent doses and are usually milder. Your team should have paused the infusion, given you extra medications, and resumed at a slower rate. If reactions are severe, talk to your doctor about additional premedication or slower infusion rates.
Q: Can I get the flu shot while on rituximab?
A: Yes, but ONLY the inactivated flu shot (injection), NOT the nasal flu vaccine (FluMist) which is live. You should get flu shots while on rituximab because you're at higher risk for infections with B-cell depletion. However, the vaccine may be less effective because your B-cells (which make antibodies) are depleted. Best timing: get vaccinated at least 2 weeks before starting rituximab if possible, or at least 4 weeks after last dose. But if you're in the middle of treatment during flu season, get it anyway - partial protection is better than none. Avoid ALL live vaccines (MMR, varicella, shingles/Zostavax, yellow fever).
Q: Why did I need hepatitis B testing before starting rituximab?
A: Rituximab can cause hepatitis B virus (HBV) to reactivate in people with current or past infection, and this reactivation can be fatal (fulminant hepatitis, liver failure). Even if you had hepatitis B decades ago and "cleared" it, the virus stays dormant in your liver. Rituximab's suppression of B-cells can allow the virus to wake up and replicate uncontrollably. Testing is MANDATORY before starting. If positive, you'll start antiviral medication (entecavir or tenofovir) BEFORE rituximab and continue during treatment and for 12+ months after. This prophylaxis has dramatically reduced HBV reactivation deaths.
Q: How is rituximab different from chemotherapy?
A: Rituximab is a monoclonal antibody (targeted therapy), not traditional chemotherapy. Chemotherapy drugs kill all rapidly dividing cells (cancer cells, but also hair follicles, gut lining, bone marrow). Rituximab specifically targets CD20 protein on B-cells only - it's like a guided missile vs. chemotherapy's carpet bombing approach. This means rituximab doesn't cause hair loss, mouth sores, or severe bone marrow suppression on its own. However, it's usually given WITH chemotherapy (R-CHOP), so you'll experience side effects from both. The "R" in R-CHOP is rituximab; the "CHOP" is the chemotherapy part.
Q: Will my immune system recover after rituximab?
A: Yes, but it takes time. Rituximab depletes your B-cells (the cells that make antibodies). B-cells typically start recovering 6-9 months after your last dose and reach normal or near-normal levels by 9-12 months. However, full immune recovery can take 12-18+ months. During this time, you're at increased infection risk. Your oncologist may check immunoglobulin levels (IgG, IgA, IgM) - if severely low with recurrent infections, you may need IVIG (IV immunoglobulin replacement). Most patients fully recover immune function and can fight infections normally again.
Q: Can rituximab cure my lymphoma?
A: It depends on the type. For aggressive lymphomas like DLBCL, R-CHOP cures about 60-70% of patients - meaning the lymphoma never comes back. For indolent (slow-growing) lymphomas like follicular lymphoma, cure is rare but many patients live for decades with excellent disease control, receiving treatment only when needed. CLL is generally not curable but can go into long remissions. Rituximab's impact has been revolutionary - it improved cure rates for DLBCL by 15-20 percentage points. If your lymphoma is potentially curable, rituximab-based treatment gives you the best chance.
Q: What's the difference between IV rituximab and the subcutaneous shot (Rituxan Hycela)?
A: Rituxan Hycela is rituximab given as a subcutaneous injection (under the skin) instead of IV infusion. Major advantage: takes 5-7 minutes instead of 2-6 hours - MUCH more convenient. You MUST receive your first dose IV to ensure you tolerate it (can't stop a subcutaneous injection once given). After that, if your doctor approves, you can switch to SC. Dose is fixed at 1,400 mg regardless of weight (with hyaluronidase enzyme to help absorption). Efficacy is the same. Many patients prefer SC for maintenance therapy. Not all insurance covers it; some require step therapy (try IV first).
Q: I'm scheduled for maintenance rituximab every 2 months for 2 years. Why so long?
A: For follicular lymphoma, the PRIMA trial showed that 2 years of maintenance rituximab (given every 2 months after initial treatment) dramatically extended progression-free survival - from median 4.1 years (observation only) to 10.5 years (with maintenance). That's an extra 6+ years before lymphoma progresses! The mechanism: rituximab continuously depletes any residual lymphoma B-cells before they can grow into detectable disease. While 2 years seems long, the benefit is substantial and side effects are minimal (mostly just infusion reactions, which are usually mild after the first few doses). Many patients tolerate maintenance well.

Living with Rituximab Treatment

Preparing for Infusion Days

Infection Prevention

When to Call Your Doctor

Contact your oncology team immediately for:
  • Fever ≥100.4°F (38°C)
  • Signs of infection (cough, burning urination, skin redness/warmth)
  • Shortness of breath or difficulty breathing
  • Chest pain or irregular heartbeat
  • New neurologic symptoms (confusion, weakness, vision changes, difficulty speaking)
  • Jaundice (yellow skin/eyes), dark urine, severe abdominal pain
  • Severe skin rash or blistering
  • Unusual bleeding or bruising

Support Resources

Medical Disclaimer: This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Rituximab has serious risks including potentially fatal infusion reactions, infections, and viral reactivations. Every patient's situation is unique. Always consult your oncologist and healthcare team about your specific condition, treatment plan, and any questions or concerns you have. If you have a medical emergency, call 911 or go to the nearest emergency room immediately.
Sources: This guide is based on FDA prescribing information for Rituxan and biosimilars, National Comprehensive Cancer Network (NCCN) guidelines for B-cell lymphomas and CLL, landmark clinical trials (GELA LNH-98.5 for DLBCL, PRIMA for follicular lymphoma maintenance, CLL8 for FCR), peer-reviewed medical literature on CD20-directed therapy, and clinical practice guidelines from major cancer centers. Content reviewed for medical accuracy and updated to reflect current standards of care as of 2025.