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Treatment Name: Venetoclax (Venclexta®) + Obinutuzumab (Gazyva®)

Venetoclax (Venclexta®) + Obinutuzumab (Gazyva®) is a Treatment Regimen for Chronic Lymphocytic Leukemia (CLL)

How does venetoclax (Venclexta®) + obinutuzumab (Gazyva®) for chronic lymphoid leukemia (CLL) work?

Venetoclax is designed to kill cancerous B-lymphocytes. It does this by binding to and inhibiting a protein in cancerous lymphocytes known as “BCL-2,” which prevents the cell from dying and also makes it resistant to certain drug treatments. Venetoclax is a type of targeted therapy.

Obinutuzumab is designed to bind to a specific protein on the surface of cancerous cells, specifically B-lymphocytes, and target these cells for destruction by your own immune system. Obinutuzumab is a type of immunotherapy.

What are the goals of venetoclax (Venclexta®) + obinutuzumab (Gazyva®) therapy?

Venetoclax plus obinutuzumab is given to decrease symptoms of CLL such as enlarged or swollen lymph nodes, enlarged liver or spleen, or symptoms of abnormal bone marrow function, such as frequent infections. Venetoclax and obinutuzumab are given in combination with the goal of keeping CLL in remission for months or even years.

What are other names for this treatment?

Venclexta® + Gazyva®, VO, VG, obinu plus ven

Schedule

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How is venetoclax + obinutuzumab therapy for CLL given?

Cycle 1 (Days 1-28)

  • Day 1: Obinutuzumab 100 mg intravenous (I.V.) infusion over four hours
  • Day 2: Obinutuzumab 900 mg IV over four or more hours (4 hours if no infusion reactions, more time if reactions occur)
  • Day 8: Obinutuzumab 1000 mg IV over four or more hours
  • Day 15: Obinutuzumab 1000 mg IV over four or more hours
  • Day 22: Venetoclax 20 mg (two 10 mg tablets) by mouth once daily, every day for seven days

Cycle 2 (Begins on Day 29; cycle length is 28 days)

  • Day 1: Obinutuzumab 1000 mg IV over four or more hours
  • Day 1: Venetoclax 50 mg by mouth once daily, every day for seven days
  • Day 8: Venetoclax 100 mg by mouth once daily, every day for seven days
  • Day 15: Venetoclax 200 mg (two 100 mg tablets) by mouth once daily, every day for seven days
  • Day 22: Venetoclax 400 mg (four 100 mg tablets) by mouth once daily, every day for seven days

Cycles 3-6 (Begins on Day 57; cycle length is 28 days)

  • Day 1: Obinutuzumab 1000 mg IV over four or more hours
  • Venetoclax 400 mg (four 100 mg tablets) by mouth once daily, every day

Cycles 7-12 (cycle length is 28 days)

  • Venetoclax 400 mg (four 100 mg tablets) by mouth once daily, every day

After cycle 12 is finished, ventoclax is stopped and the patient is monitored off all treatment.

Estimated total infusion time for Obinutuzumab:

  • Obinutuzumab infusion times are based on clinical studies and wil vary depending doctor preference or patients' tolerability. Pre-medications and intravenous (I.V.) fluids, such as hydration, may add more time. The IV infusions start as short as 4 hours and can extend several hours longer if reactions occur. See our section on the individual drug, obinutuzumab, below for more on infusion reactions

Estimated duration of venetoclax treatment:

  • Venetoclax is taken continuously until disease progression or unacceptable toxicity
  • Venetoclax may be taken at home, in an infusion center, or in the hospital depending upon the risk level
  • Take with food and a large glass of water around the same time of day, each day. Do NOT crush, break, or chew tablets. If a dose is missed by more than 8 hours, wait until the next daily dosing time and do not double up the next dose

Side Effects

What are the most common side effects from venetoclax + obinutuzumab for CLL?

In a multi-drug regimen, each medication has unique side effects. When these medicines are given together, drug-related side effects reported in clinical studies give the best estimate of what to expect. In clinical studies, the most commonly reported serious side effects (Grades 3 and 4) of venetoclax + obinutuzumab are shown here:

A note about side effect percentages

  • Neutropenia [low white blood cells] (53%)
  • Infections (18%)
  • Thrombocytopenia [low blood platelets] (14%)
  • Infusion reactions (9%)
  • Anemia [low red blood cells] (8%)
  • Neutropenic fever (5%)
  • Heart problems (5%)
  • Lung disorders (5%)
  • Nervous system disorders (5%)
  • Diarrhea (4%)
  • High blood sugar (4%)
  • Pneumonia (4%)
  • Muscle disorders (3%)
  • Liver dysfunction (2%)
  • Skin problems (1%)

In a clinical trail, on average 15% of patients discontinued treatment due to adverse events.

Importantly, not all people who experience a side effect from Venclexta® (venetoclax) + Gazyva® (obinutuzumab) will experience it in the same way. It may be mild in some or severe in others, depending upon the individual. Everybody is different. Additionally, side effects may vary over time. For some, side effects may be a reason to delay or switch treatment, reduce the dose, or avoid further treatment with a certain medication altogether.

Side effects may be treatable when they occur or preventable by taking certain medications before they happen. When medications are taken to prevent a problem, this is known as prophylaxis, or "prophy" for short.

After starting treatment with venetoclax + obinutuzumab, be sure to come back and watch all of the side effect videos shown below. Each of these videos contain valuable information about side effect management that will hopefully help you to both feel better and stay out of the hospital.

Watch videos on common venetoclax + obinutuzumab therapy side effects below

Side effect videos Side Effect Videos
AnemiaAnemiaNeutropenic FeverNeutropenic FeverDiarrheaDiarrhea

Monitoring

How often is venetoclax plus obinutuzumab monitoring needed?

Labs (blood tests) will be checked before treatment, and as frequently as every 6 to 8 hours if the venetoclax ramp-up phase occurs in the hospital. As lymph nodes shrink and the number of CLL cells in the blood decrease, the frequency of lab tests will likely decrease.

Monitoring may occur in the hospital or in an outpatient clinic, depending upon whether someone is considered, low, medium, or high risk for tumor lysis syndrome, and whenever a higher dose is used during the first 4-week ramp-up phase.

Monitoring during and after the Venclexta 5-week ramp-up will depend upon response to therapy, side effects experienced, and whether Venetoclax needs to be discontinued if not tolerated. Labs often include: Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), uric acid, Lactate Dehydrogenase (LDH), blood magnesium, calcium, and phosphorous, plus any others your doctor may order. A bone marrow biopsy may be considered to monitor for minimal residual disease.

How often is imaging needed?

Imaging may be checked before treatment, at Week 6, then Week 12 or 16, then Week 24, then every 12 weeks thereafter, until stable. Imaging may include: X-rays, computerized tomography (CT scan), and any others your doctor may order.

How might blood test results/imaging affect venetoclax plus obinutuzumab treatment?

Depending upon the results, your doctor may advise to continue as planned, reduce the dose, delay or switch therapy, or discontinue this treatment.

ChemoExperts Tips

What are the 8 most important things to know about venetoclax + obinutuzumab while receiving therapy?

  • Premedications such as diphenhydramine (Benadryl®), acetaminophen (Tylenol®), and methylprednisolone (Solu-Medrol®) may be given before obinutuzumab to help avoid infusion related reactions
  • The first dose of obinutuzumab is often the hardest. It may lead to fever, shaking, and chills even if premedications are given to help prevent this. Reactions generally go away when the obinutuzumab infusion is stopped. When symptoms go away, it may be restarted at a slower rate. If a reaction occurs, most patients are still able to receive the entire dose, although it may take longer. In some cases, after the first dose, obinutuzumab can be give over as short as 4 hours
  • Patients should contact their doctor immediately if they develop lightheadedness or feel their heart racing
  • Drink 6 to 8 glasses of water each day starting two days prior to the first dose of venetoclax, and each time the dose is increased, to help reduce the chance of getting tumor lysis syndrome
  • If Venetoclax therapy is stopped for more than one week during the initial 5-week ramp-up phase due to side effects, abnormal blood tests, or infection, or stopped for more than two weeks after taking the 400 mg dose, the dose may again need to be reduced when restarting. Once restarted it will be increased slowly to avoid tumor lysis syndrome
  • Venetoclax interacts with medications commonly taken for other reasons. A pharmacist should ALWAYS review your medication list BEFORE starting Venetoclax to ensure that drug interactions are prevented or managed appropriately. On occasion, medications that you were taking regularly before Venetoclax may need to be switched or discontinued in order to safely take Venetoclax. Ask a pharmacist before starting ANY new medication if you are already taking Venetoclax
  • If neutropenia occurs (a condition where the level of certain white blood cells known as “neutrophils" becomes too low), antibiotics or neutrophil growth factor medications, such as filgrastim, may be prescribed by your doctor
  • Clinical trials may exist for CLL. Ask your doctor if any studies are currently enrolling in your area. If not, go to clinicaltrials.gov to search for other centers offering study medications

Patient Assistance & Co-payment Coverage

Patients under the age of 65 years, or those with private insurance plans:
If you have insurance and are looking for patient assistance or copay assistance for Venetoclax (Venclexta®) + Obinutuzumab (Gazyva®), we have provided links that may help.

Visit our Patient Assistance page and click the links to various patient assistance programs for help paying for Venetoclax (Venclexta®) + Obinutuzumab (Gazyva®). Depending upon your income, they may be able to help cover the cost of:

  • Venetoclax
  • Obinutuzumab

For Branded medications (may be available for generic medications too), check with the manufacturer to determine if a co-pay card is offered and if it could reduce your monthly copay.

  • If you are uninsured, check with the manufacturer to determine if you are eligible to receive medication at no cost.

Medicare and Medicaid patients (Patients 65 years or older):
The clinic providing treatment will likely pre-authorize medications and immune therapies such as Venetoclax (Venclexta®) + Obinutuzumab (Gazyva®) and are the best source to help you understand drug cost.

  • Ask to speak with a patient assistance technician or financial counselor at the clinic or hospital administering this therapy.

Emotional Wellness

What is Emotional Wellness?
Emotional wellness is having a positive outlook balanced with a realistic understanding of current life events. This requires both an awareness and acceptance of your emotions. It is with this knowledge that you can develop a plan to take the necessary actions to positively impact your life.

Emotional wellness uses an ongoing process to continually reflect on the stressors of life in a constructive manner to move forward and create happiness.

Because emotional wellness is deeply connected with physical, social, and spiritual wellness, pursuing it often becomes particularly difficult in times of major illness. Despite this difficulty, working toward emotional wellness has been connected to improved treatment outcomes and a higher likelihood of achieving goals of therapy.

Learn more about pursuing emotional wellness while receiving treatment with Venetoclax (Venclexta®) + Obinutuzumab (Gazyva®)

Individual Drug Label Information

Venetoclax (Venclexta®)

  • Venetoclax is an oral tablet, available in the following doses: 10 mg, 50 mg, 100 mg 
  • Tumor Lysis Syndrome is expected. Patients at high risk for tumor lysis may need to be hospitalized for the first several doses to receive adequate IV fluids, plus electrolyte and kidney function monitoring 
  • Neutropenia is common. Antibiotics may be needed to prevent or treat infections 
  • Live attenuated vaccines should not be administered before, during, or after treatment with venetoclax as they have not been studied and it is unknown if they are safe to use. Ask your pharmacist if you are not sure which vaccines are safe to use 
  • Venetoclax may make certain vaccines less effective. Repeat vaccination may be required at a later time 
  • Take with food and a large glass of water around the same time of day, each day. Do NOT crush, break, or chew tablets. If your dose is 200 mg or 400 mg, multiple tablets will need to be taken at the same time. Do NOT split up dosing during a day as this may change how the medication works or the incidence of certain side effects 
  • Drug interactions may be severe. Certain medications should NOT be taken together with venetoclax. Ask a pharmacist if your home medications are safe to use 
  • It is recommended to take with food to help with absorption 
  • Avoid grapefruit, grapefruit juice, Seville oranges, marmalade and star fruit as these may increase the amount of venetoclax that is in your body leading to unwanted side effects 
  • If you miss a dose, take venetoclax within 8 hours of the normal time you take it, and resume the normal schedule the next day. If a dose is missed and more than 8 hours has past since you usually take it, skip the dose and resume the next day at your usual time 
  • If vomiting occurs, no dose should be taken until the next scheduled dose on the following day. Do NOT make up for missed doses. 
  • Stored at or below 86 degrees Fahrenheit  
  • Dosage adjustments may be required kidney or liver problems 
  • May interact with antifungal medications ending in “azole,” such as voriconazole or posaconazole. These medications MUST NOT be used during the first 5 weeks of venetoclax therapy 
  • May interact with common medications such as ciprofloxacin, fluconazole, diltiazem, verapamil, amiodarone, St. John’s wort, digoxin, warfarin, vitamins, herbal supplements, and many others. Alternative medications should be considered, or the doses greatly reduced (for example, by 50% or more) 
  • Drug interactions with venetoclax may lead to severe side effects. Certain medications should NOT be taken together. Ask a pharmacist if your home medications are safe with this drug
  • May cause fetal harm, avoid this drug during pregnancy and breastfeeding. Females of child-bearing potential should take a pregnancy test before starting venetoclax and use effective contraceptive during therapy and for at least 30 days after the last dose
  • Males may consider sperm banking as venetoclax may cause infertility 
General Venetoclax (Venclexta) Side Effects 
  • Neutropenia [increased infection risk] 
  • Neutropenic fever [medical emergency requiring IV antibiotics immediately] 
  • Diarrhea 
  • Nausea 
  • Anemia [low red blood cells] 
  • Upper respiratory tract infections such as sinus infection, or sore throat 
  • Low platelet count [increased risk of bleeding] 
  • Fatigue 
  • Vomiting 
  • Constipation 
  • Swelling or water retention 
  • Back pain 
  • Headache 
  • Cough 
  • Venetoclax is NOT expected to cause hair loss 
  • Click on the venetoclax (Venclexta) package insert below for reported side effects and possible drug interactions

Side Effect Videos
Nausea and VomitingNausea and VomitingDiarrheaDiarrheaFatigue Fatigue BleedingBleedingPainPainAnemiaAnemiaNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

Obinutuzumab (Gazyva®)

  • ​Obinutuzumab is an intravenous infusion
  • Acetaminophen (Tylenol®), an antihistamines (e.g. diphenhydramine = Benadryl®), and a glucocorticoid (dexamethasone or methylprednisolone) should be given prior to the Cycle 1 dose.  If no reactions, patients take acetaminophen + antihistamine as premeds
  • Patients should be screened for hepatitis B as obinutuzumab can cause a re-activation of this infection
  • May cause vaccines to work less well. It is advised that vaccines be given two to four weeks prior to obinutuzumab if possible
General Obinutuzumab (Gazyva) Side Effects
  • May cause an infusion reaction, which could include skin reaction, shaking, chills, fever, or shortness of breath. These reactions may be severe, but are very rarely life-threatening
  • Infusion reactions do not commonly happen after the first dose, but are possible
  • May increase the risk of infection. Your doctor may prescribe antibiotics to prevent certain infections associated with obinutuzumab use
  • Patients should report any late-onset hypersensitivity (infusion reactions), diagnosed as serum sickness, with symptoms that include chest pain, diffuse joint pain and fever.
  • Low blood platelets (thrombocytopenia) can occur which increases bleeding risk.  Taking other medications that affect blood clotting can be a risk and should be reported to your doctor or pharmacist
  • Click on the obinutuzumab (Gazyva) package insert link below for more reported side effects and potential drug Interactions

Side Effect Videos
BleedingBleedingNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

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References

1) Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med 2019;380:2225-2236.

2) Stephens DM. Venetoclax and obinutuzumab for frontline treatment of chronic lymphocytic leukemia. Blood. 2019 Nov 14;134(20):1691-1696. doi: 10.1182/blood.2019001750.

Created: December 7, 2019 Updated: January 6, 2020

What is Chronic Lymphocytic Leukemia (CLL)?

Chronic Lymphocytic Leukemia (CLL) is the most common type of leukemia diagnosed in adults. It is a cancer of the B-lymphocyte. In rare cases, CLL may be hereditary, but most causes are unknown. The stage of CLL can vary at diagnosis and throughout treatment. Stages of CLL include Rai stage 0, I, II, III, or IV. Many therapies are not curative, however, newer therapies are able to suppress the cancer for many months or even years.

Medications for CLL may include intravenous infusions, oral tablets or capsules, or a combination of IV and oral medications. Patients may be diagnosed with CLL without having any symptoms. Others may go to their doctor with symptoms of fatigue, a large spleen, or decreased appetite. The effectiveness of the treatment may depend upon the stage at diagnosis.

NOTE: Treatment Options listed below are not all-inclusive. Other treatments may be available. ChemoExperts provides drug information and does not recommend any one treatment over another. Only your Doctor can choose which therapy is appropriate for you.

What is Tumor Lysis Syndrome (TLS)?

Tumor lysis syndrome, or TLS, occurs when many cancer cells die quickly and release their contents into the bloodstream. Many times the body has the ability to flush these substances out through the kidneys or metabolize them via the liver. However, sometimes the body needs medicines to help eliminate these substances and to prevent organ damage.

Venetoclax Starter Pack Dosing

The Venetoclax Starter Pack includes the following:

Week 1: Venetoclax 20 mg (two 10 mg tabs) by mouth once daily = fourteen 10 mg tablets
Week 2: Venetoclax 50 mg by mouth once daily = seven 50 mg tablets
Week 3: Venetoclax 100 mg by mouth once daily = seven 100 mg tablets
Week 4: Venetoclax 200 mg (two 100 mg tabs) by mouth once daily = fourteen 100 mg tablets

Of note: Week 5 and beyond: 400 mg (four 100 mg tabs) by mouth once daily are dispensed as a separate prescription as a one month supply.

Important: Tablets should be kept in their original container until use.

What is a CBC?

A Complete Blood Count (CBC) is a frequently ordered blood test that tells clinicians the status of your: 1) White blood cell count, 2) Hemoglobin, and 3) Platelet count at the time the test was taken.

Common uses:
1) White blood cell count (WBC): is used to determine infection risk, or response to chemotherapy. Certain chemotherapy agents may harm our good infection-fighting cells. Sometimes chemotherapy may need to be delayed to allow these cells to recover.

2) Hemoglobin: is used to determine if someone is anemic. Anytime the hemoglobin is below 12 g/dL, the person is said to be anemic. Red blood cell transfusions, and sometimes iron can be given to restore the hemoglobin level, but anemia treatment should always aim at treating the underlying cause or condition.

3) Platelet count: is used to determine if the risk of bleeding is increased or if a platelet transfusion is required to prevent bleeding. Certain medications that increase bleeding risk, such as: aspirin, certain chemotherapy agents, and blood thinners, may need to be stopped temporarily until the platelet count is within a safe range.

What is a CMP?

A Comprehensive Metabolic Panel (CMP) is a frequently ordered blood test that tells clinicians the status of your: 1) Electrolytes & Acid/Base status2) Kidney function, 3) Liver function, 4) Blood sugar, and 5) Calcium at the time the test was taken. It is commonly used to monitor liver and kidney function when beginning new medications such as chemotherapy. A total of 14 tests are run simultaneously and are shown below.

Electrolytes & Acid/Base status:
1) Sodium, 2) Potassium, 3) Carbon dioxide, 4) Chloride

Kidney Function:
5) BUN (blood urea nitrogen), 6) Serum creatinine (Scr)

Liver Function:
7) AST, 8) ALT, 9) Total bilirubin, 10) Alk Phos, 11) Albumin, 12) Total protein

Blood sugar:
13) Serum glucose

Calcium:
14) Serum calcium

A note about side effect percentages

The number you see next to the percent sign (%) means how many people out of 100 are likely to experience this side effect.

For example, if the side effect is reported to occur in 8% of patients, this means that roughly 8 out of 100 people receiving this treatment will experience this side effect.