Obinutuzumab

Obinutuzumab (Gazyva) is a targeted immunotherapy treatment used to treat chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), active lupus nephritis, or frequently relapsing or steroid-dependent childhood-onset idiopathic nephrotic syndrome in certain patients. It is given in combination with other cancer treatments by a healthcare provider via an IV infusion.

Obinutuzumab gained FDA approval on November 1, 2013, under the brand name Gazyva. A new lupus nephritis indication was added in October 2025. There is no generic or biosimilar.

FDA-Approved Uses in Adults

Blood Cancers

Chronic Lymphocytic Leukemia (CLL)

• Newly diagnosed, previously untreated CLL patients
• Given in combination with chlorambucil chemotherapy.

Follicular Lymphoma (FL)

• For relapsed or treatment-resistant FL after rituximab therapy, in combination with bendamustine, followed by obinutuzumab monotherapy
• For newly diagnosed, previously untreated, stage II bulky, III, or IV disease, in combination with chemotherapy followed by obinutuzumab monotherapy in patients achieving at least a partial remission.

Autoimmune Disease

Active Lupus Nephritis (Kidney Inflammation from Lupus)

• Added to your current lupus medications
• Helps reduce kidney inflammation.

Frequently Relapsing or Steroid-Dependent Childhood-Onset Idiopathic Nephrotic Syndrome

• In adults and children 2 years of age and older
• Used to reduce the risk of relapse in patients who are in complete remission.

How Well Does Obinutuzumab Work?

For Follicular Lymphoma (GALLIUM Trial)

• 63% of patients were cancer-free at 7 years (vs. 56% with rituximab)
• Took longer before needing the next treatment
• Best results in patients with complete molecular response

For Chronic Lymphocytic Leukemia

• 80% of patients responded to treatment (vs. 66% with rituximab)
• Cancer stayed controlled for nearly 1 extra year (27 months vs. 15 months)

For Active Lupus Nephritis (NOBILITY & REGENCY Trials)

• 46% achieved complete kidney recovery when obinutuzumab was added to standard treatment (vs. 33% with standard treatment alone)
• Patients also experienced: Improved immune system markers Reduced lupus antibodies Ability to lower steroid doses Less protein in urine (sign of kidney improvement)
• Safety profile similar to when used for blood cancers.

For Frequently Relapsing or Steroid-Dependent Childhood-Onset Idiopathic Nephrotic Syndrome (INSHORE clinical trial)

• Significantly more children and young people with frequently relapsing or steroid-dependent nephrotic syndrome stayed relapse-free and in complete remission at one year on Gazyva than on mycophenolate mofetil (MMF).

• 95% of patients on Gazyva had no relapse after Week 8 and were in complete remission at Week 52
• 73% of patients on MMF had no relapse after Week 8 and were in complete remission at Week 52
• Treatment difference of 22% (95% CI, 6-38; P=0.004)

Obinutuzumab is a CD20-directed antibody that targets a specific protein (CD20) found on certain white blood cells called B-lymphocytes. By binding to this protein, obinutuzumab:

• Helps your immune system identify and destroy marked cells
• Directly attacks cancer cells
• Preserves stem cells in bone marrow, allowing your body to keep producing healthy blood cells.

Obinutuzumab is given as an intravenous infusion by a healthcare provider in a clinic or infusion center.

Infusion Details

Duration: Most infusions take 3-5 hours

Faster option: A 90-minute infusion may be available starting in Cycle 2 if you don't experience severe reactions during Cycle 1

Location: Clinic or infusion center

Administration: Given only as intravenous infusion (not as IV push or bolus)

Monitoring: Healthcare staff will watch you closely during and after each infusion

One Week Before

• Review all medications with your doctor
• Discuss blood pressure medications that may need adjustment

Day of Infusion

• Arrange a ride home - You may feel tired
• Wear comfortable clothes - You'll be sitting for several hours
• Bring items to stay occupied - Books, tablets, snacks, water
• Plan for a full day - Most patients spend 4-6 hours at the facility

Pre-Medications

Your doctor will prescribe medications to prevent infusion reactions and tumor lysis syndrome. These are typically given one hour before infusion:

• Acetaminophen (Tylenol)
• Antihistamines
• Corticosteroids.

Your doctor will regularly assess:

• Disease symptoms
• Lymph node, liver, and spleen size
• Complete blood counts (CBC)
• Side effects and overall health.

Do not use if you:

• Have had an allergic reaction to obinutuzumab or its ingredients
• Have active hepatitis B liver disease

Tell your healthcare provider if you:

• Have heart disease
• Have an infection (especially hepatitis B)
• Have lung or breathing problems
• Recently received or plan to receive a vaccine
• Take blood thinners (anticoagulants)
• Are pregnant or planning pregnancy
• Are breastfeeding or planning to breastfeed.

Most Common Side Effects

Chronic Lymphocytic Leukemia:

• Infusion-related reactions
• Low white blood cell count (neutropenia).

Follicular Lymphoma:

• Infusion-related reactions
• Fatigue
• Low white blood cell count
• Cough
• Upper respiratory infections
• Muscle and joint pain
• Constipation
• Diarrhea.

Lupus Nephritis:

• Upper respiratory tract infections
• COVID-19
• Urinary tract infections
• Bronchitis
• Pneumonia
• Infusion-related reactions
• Low white blood cell count.

Childhood-onset idiopathic nephrotic syndrome:

• Upper respiratory tract infection
• Infusion-related reactions
• Ear infection
• Pneumonia
• Influenza
• Neutropenia
• Bronchitis
• COVID-19
• Conjunctivitis
• Urinary tract infection.

Serious side effects and warnings

Black Box Warnings

Obinutuzuma carries a boxed warning for hepatitis B reactivation and progressive multifocal leukoencephalopathy (PML).

Hepatitis B Reactivation

Gazyva can reactivate dormant hepatitis B virus, which may cause liver failure or death.

• You'll be screened before treatment
• Monitored during and after treatment
• May need hepatitis B treatment.

Warning signs of hepatitis B include: extreme fatigue, yellowing of the skin or eyes

Progressive Multifocal Leukoencephalopathy (PML)

PML is a rare and serious viral brain infection that can be fatal.

Warning signs: Confusion, difficulty talking or walking, dizziness, and vision problems.

Other Serious Risks

Infusion-Related Reactions (IRRs):

Most occur during or within 24 hours of infusion. Most patients can continue treatment after symptoms are managed.

Symptoms include: fast heartbeat, tiredness, dizziness, headache, facial flushing, nausea, chills, fever, vomiting, diarrhea, rash, blood pressure changes, difficulty breathing, and chest discomfort

Severe Allergic Reactions

Some patients experience life-threatening allergic reactions, including anaphylaxis or serum sickness affecting multiple body systems. Seek urgent medical attention.

Tumor Lysis Syndrome (TLS)

Cancer cells break down rapidly, releasing contents into the bloodstream that can damage organs.

Symptoms: Nausea, vomiting, diarrhea, and extreme tiredness.

Your doctor will:

• Prescribe preventive medication
• Monitor with regular blood tests.

Infections

Your immune system is weakened during treatment, increasing infection risk. Some infections can be severe or fatal.

• Report any signs of infection immediately
• Don't start treatment if you have an active infection
• Higher risk if you have chronic/recurring infections.

Low Blood Cell Counts

• Low white blood cells (neutropenia): Increases infection risk
• Low platelets (thrombocytopenia): Increases bleeding risk; fatal bleeding has occurred

Disseminated Intravascular Coagulation (DIC)

This is a rare, serious blood-clotting disorder that can lead to uncontrollable bleeding.

These are not all the possible side effects of Gazyva. For more information, ask your doctor or pharmacist. Tell your doctor right away about any side effects you experience. You may report side effects to the FDA at (800) FDA-1088, or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Previously Untreated CLL

Six 28-day cycles with chlorambucil

• Cycle 1: 100 mg (Day 1), 900 mg (Day 2), 1000 mg (Day 8), 1000 mg (Day 15)
• Cycles 2-6: 1000 mg (Day 1 only).

Relapsed/Refractory Follicular Lymphoma

Six 28-day cycles with bendamustine

• Cycle 1: 1000 mg (Days 1, 8, 15)
• Cycles 2-6: 1000 mg (Day 1 only)
• Maintenance: If disease doesn't progress, may receive obinutuzumab alone every 2 months for up to 2 years.

Previously Untreated Follicular Lymphoma

Six to eight cycles (length depends on chemotherapy type)

• Cycle 1: 1000 mg (Days 1, 8, 15)
• Subsequent cycles: 1000 mg (Day 1 only)
• Maintenance: May continue every 2 months for up to 2 years if treatment works.

Active Lupus Nephritis

Long-term maintenance schedule

• 1000 mg at first infusion
• 1000 mg at Week 2
• 1000 mg at Weeks 24 and 26
• 1000 mg every 6 months thereafter.

Childhood-onset idiopathic nephrotic syndrome

Patients weighing 45 kg or more:

• 1,000 mg at the initial infusion, on Week 2, 24 and 26.

For patients weighing less than 45 kg

• Recommended dose is 20 mg/kg, at the initial infusion, on Week 2, 24, and 26.

For patients receiving concomitant oral corticosteroids, the corticosteroids should be tapered off after initiating Gazyva at the discretion of the healthcare provider.

Live Vaccines

Do not receive live vaccines while on obinutuzumab or recently after treatment:

• BCG (tuberculosis)
• MMR (measles, mumps, rubella)
• MMRV (measles, mumps, rubella, varicella)
• Rotavirus
• Varicella (chickenpox)

Patients treated with obinutuzumab should not receive live vaccines. Ask your doctor about vaccine timing before and after treatment.

Generic name: Obinutuzumab

Brand name: Gazyva

Active ingredient: Obinutuzumab

Inactive ingredients: 20 mM L-histidine/L-histidine hydrochloride, 240 mM trehalose, 0.02% poloxamer 188 (pH 6.0)

Supplied as: 1,000 mg single-dose vials (25 mg/mL concentration)

Manufacturer: Genentech, Inc. (a member of the Roche Group), South San Francisco, California.

Pregnancy

Obinutuzumab may harm your unborn baby.

• Use effective contraception (birth control) during treatment and for 6 months after your last dose
• Tell your doctor immediately if you become pregnant during treatment
• If you received obinutuzumab during pregnancy, discuss vaccine timing for your infant with your healthcare provider

Breastfeeding

Do not breastfeed during treatment or for 6 months after your last dose due to potential risks to infants.