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Treatment Name: AAVD (Brentuximab vedotin, Doxorubicin, Vinblastine, Dacarbazine)

AAVD (Brentuximab vedotin, Doxorubicin, Vinblastine, Dacarbazine) is a Chemotherapy Regimen to treat Hodgkin's Lymphoma

How does AAVD chemo work?

  • Brentuximab vedotin (Adcetris®) is an antibody that targets Hodgkin lymphoma cells. After it binds to the lymphoma cell surface, it then enters the cancer cell. Once inside the cell, the antibody releases a drug called MMAE, which stops the lymphoma from growing and dividing
  • Doxorubicin, vinblastine, and dacabazine are designed to kill or slow the growth of Hodgkin lymphoma cells

A – Adcetris® (Brentuximab Vedotin)
A – Adriamycin® (Doxorubicin)
V - Vinblastine
D – Dacarbazine

Alternate regimen name: A+AVD

Goals of AAVD therapy:
AAVD treatment is given to shrink enlarged lymph nodes, and decrease symptoms from Hodgkin lymphoma such as fever, night sweats, and weight loss. By completely eliminating all Hodgkin lymphoma cells, AAVD chemotherapy is commonly given with the goal of cure.

Schedule

  • Brentuximab vedotin intravenous (I.V) infusion over 30 minutes on Days 1 and 15
  • Doxorubicin I.V push or infusion over 15 minutes on Days 1 and 15
  • Vinblastine I.V. infusion over 5 to 10 minutes on Days 1 and 15
  • Dacarbazine I.V. infusion over 30 minutes on Days 1 and 15

Typically all four drugs are given on Days 1 and 15 of each cycle, unless the doctor discontinues one or more for side effects or toxicity.

Estimated total infusion time for AAVD chemotherapy:

  • Up to 3 hours for Days 1 and 15 of each cycle
  • Infusion times are based on clinical studies, but may vary depending on doctor preference or patient tolerability. Pre-medications and intravenous (I.V.) fluids, such as hydration, may add more time

The AAVD chemotherapy regimen is usually given in an outpatient infusion center, allowing the person to go home afterwards. On occasion, AAVD may be given in the hospital if someone is too sick for outpatient treatment.

AAVD chemo is repeated every 28 days. This is known as one Cycle. Each cycle may be repeated up to six times, depending upon the stage of the disease and response to previous cycles. Duration of therapy may last up to six months, depending upon response, tolerability, and number of cycles prescribed.

Click here for the common AAVD treatment starting doses.

Note: Individual doses may vary based upon your Doctor's recommendation, or drug availability.

Side Effects

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 side effects of AAVD are shown here:

  • Tingling or numbness or pins and needles sensation in fingers or toes, (up to 67%)*
  • Low white blood cells [neutropenia], (58%)
  • Infection, (55%)
  • Nausea, (53%)
  • Constipation, (42%)
  • Vomiting, (33%)
  • Fatigue, (32%)
  • Diarrhea, (27%)
  • Fever, (27%)
  • Hair loss, (26%)
  • Weight loss, (22%)
  • Low red blood cells [anemia], (21%)
  • Stomach pain, (21%)
  • Sores on mouth and tongue, (21%)
  • Neutropenic fever, (19%)**
  • Bone pain, (19%)
  • Trouble sleeping [insomnia], (19%)
  • Decreased appetite, (18%)
  • Cough, (15%)
  • Headache, (14%)
  • Joint pain, (13%)
  • Heartburn, (13%)
  • Back pain, (13%)
  • Shortness of breath, (12%)
  • Muscle pain, (12%)
  • Pain in arms or legs, (12%)
  • Sore throat, (11%)
  • Sinus infection, (11%)

On average, less than 1% of patients discontinue treatment due to unacceptable side effects.

*Note: By the last follow-up visit, two out of three patients have either improvement or complete disappearance of tingling or numbness or pins and needles sensation in fingers or toes.

**Note: Neutropenic fever, also called febrile neutropenia, was more common in adults older than 60 years of age.

Side effect videos Side Effect Videos
Nausea and VomitingNausea and VomitingConstipationConstipationFatigue Fatigue DiarrheaDiarrheaNeutropenic FeverNeutropenic FeverHair LossHair LossAnemiaAnemiaPainPain

Monitoring

How often is monitoring needed?
Labs (blood tests) may be checked before each treatment but may be checked more often if needed. Labs often include: Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), plus any others your doctor may order.

How often is imaging needed?
Imaging may be checked before treatment, at the end of cycle 2 (end of second 28-day cycle), then at the completion of treatment. Imaging may include: X-rays, magnetic resonance imaging (MRI), computerized tomography (CT) scans, or positron emission tomography (PET) scans. Per your doctor’s recommendation, imaging may also be checked after therapy during the follow-up period, for example, as often as every 3 months during the first year and every 6 months thereafter.

How might blood test results/imaging affect treatment?
Depending upon the results, your doctor may advise to continue AAVD as planned, reduce the dose of future treatments, delay the next dose until the side effect goes away, or switch to an alternative therapy.

ChemoExperts Tips

  • Filgrastim (Neupogen®) or pegfilgrastim (Neulasta®) is recommended after each chemotherapy cycle to stimulate production of white blood cells, avoid periods of low white blood cell count (neutropenia), and prevent neutropenic fever
    • In the AAVD clinical trial, fewer patients developed neutropenic fever if they were given filgrastim (Neupogen®) or pegfilgrastim (Neulasta®) after each cycle compared to those who did not receive these medications (11% compared to 21%, respectively)
  • Tell your doctor if you have numbness, tingling, burning, or weakness in hands or feet as this may require a decrease in brentuximab dose or delaying future doses
  • Infusion reactions with brentuximab are rare, but can occur. The most common infusion related reactions are chills, nausea, trouble breathing, itching, fever, and cough. If infusion reactions are experienced, premedications can be given before future doses of brentuximab vedotin
  • A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately
  • Clinical trials may exist for Hodgkin’s Lymphoma. 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 AAVD (Brentuximab vedotin, Doxorubicin, Vinblastine, Dacarbazine), 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 AAVD (Brentuximab vedotin, Doxorubicin, Vinblastine, Dacarbazine). Depending upon your income, they may be able to help cover the cost of:

  • Bren­tuxi­mab Vedotin
  • Doxorubicin
  • Vinblastine
  • Dacar­bazine

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 AAVD (Brentuximab vedotin, Doxorubicin, Vinblastine, Dacarbazine) 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 AAVD (Brentuximab vedotin, Doxorubicin, Vinblastine, Dacarbazine)

Individual Drug Label Information

Bren­tuxi­mab Vedotin (Adcetris®)

  • Brentuximab vedotin is an intravenous (I.V.) infusion 
  • FDA Black Box Warning: A rare viral infection known as JC virus, has been diagnosed in some patients who received treatment with Brentuximab.  Patients themselves or family and friends should immediately report the following symptoms to the doctor: confusion, trouble speaking, loss of memory, changes in vision, difficulty walking, or weakness on one side of the body
  • Dosage adjustments may be required for liver dysfunction, low white blood cell counts, or nerve pain 
  • May interact with certain antifungal and seizure medications. Ask your doctor or pharmacist to review your medications for any possible interactions  
  • May interact with grapefruit and grapefruit juice causing increased blood levels of MMAE, the drug attached to brentuximab vedotin. This could increase your risk of experiencing side effects. Avoid eating grapefruit and drinking anything containing grapefruit juice during treatment 
  • Avoid therapy with St. Johns Wort as it will decrease blood levels of MMAE. This could decrease the effectiveness of brentuximab vedotin 
General Brentuximab Vedotin Side Effects 
  • Nerve pain such as numbness, tingling, burning, or weakness in hands or feet, also known as peripheral sensory neuropathy, may increase after each dose. It is usually reversible if treatment is stopped or the dose is decreased
  • Neutropenia, or low white blood cell counts, may occur which increases your risk of an infection.  Tell your doctor if you have a fever of 100.5° F or higher or any other concern for infection such as cough, chills, sore throat, or painful urination
  • Rash is common after treatment.  A severe rash such as Stevens-Johnson Syndrome may occur and requires immediate medical attention 
  • Click on the brentuximab vedotin (Adcetris) package insert for reported side effects and possible drug interactions

Side Effect Videos
DiarrheaDiarrheaHair LossHair LossFatigue Fatigue

See DailyMed package insert.

Doxorubicin (Adriamycin®)

  • Doxorubicin is administered as an intravenous infusion and is red in color
  • Can affect heart function. A heart study (echocardiogram) may be required before receiving the first dose
  • Dosage may be reduced in patients with poor liver function
  • Has been linked to the development of other cancers in a small number of people (1.5% chance at 10 years)
General Doxorubicin (Adriamycin) Side Effects
  • Nausea, vomiting, diarrhea, and mouth sores (stomatitis)
  • Leakage into skin or surrounding muscle during infusion may cause severe irritation (extravasation)
  • May temporarily turn urine orange
  • Hair loss, which is usually reversible
  • Increased risk of infection due to decrease white blood cell count (neutropenia)
  • Click on the doxorubicin (Adriamycin) package insert for reported side effects and possible drug interactions

Side Effect Videos
Nausea and VomitingNausea and VomitingDiarrheaDiarrheaHair LossHair LossPainPainNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

Vinblastine

  • ​Vinblastine MUST only be given by intravenous infusion (by vein) usually over 1 to 5 minutes. May NOT be administered any other way. Vinblastine will cause death if administered into spinal fluid (intrathecal)
  • Dosage adjustments may be required for patients with liver problems
  • May interact with other medications you are taking, such as antifungal medicines. Ask your doctor or pharmacist to review them
General Vinblastine Side Effects
  • Nerve pain in hands or feet may increase after each dose. It is usually reversible if treatment is stopped or dose is adjusted
  • Low white blood cell count; this may temporarily increase your risk for infection
  • Patients should immediately report and symptoms of fever, chills, sore throat or mouth to their doctor
  • Constipation; the use of fiber supplements or laxatives may be useful to prevent or treat constipation during this treatment.
  • Hair loss
  • Leakage into skin or surrounding muscle may cause severe irritation (extravasation)
  • Click on the vinblastine package insert below for reported side effects and possible drug interactions

Side Effect Videos
Hair LossHair LossConstipationConstipationPainPainNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

Dacar­bazine (DTIC)

  • Dacarbazine is an intravenous (I.V.) infusion
  • FDA Boxed Warning for low blood counts, most commonly low white blood cells and low platelets FDA Boxed Warning for liver toxicity
  • Dosage adjustments may be required for kidney function 
General Dacarbazine (DTIC) Side Effects
  • Dacarbazine is associated with a high risk of nausea and vomiting. Be sure to always have a supply of anti-nausea medications at home
  • Weight loss
  • Hair loss
  • Click dacarbazine (DTIC) package insert below for reported side effects and possible drug interactions

Side Effect Videos
Hair LossHair Loss

See DailyMed package insert.

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References

1) Connors JM, Jurczak W, Straus DJ, et al. Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin’s Lymphoma. N Engl J Med. 2018;378:331-344.

Created: February 8, 2018 Updated: February 8, 2018

What is Hodgkin's Lymphoma?

Hodgkin Lymphoma is a disease of the white blood cells known as B-lymphocytes which are normally found in lymph nodes, blood, and throughout the body. Hodgkin lymphoma most commonly affects lymph nodes found in the neck or center of the chest. There are different types of Hodgkin lymphoma, many of which are rare. Most Hodgkin lymphomas are diagnosed by the presence of a specific cell known as the Reed-Sternberg cell. Known causes of lymphoma may include family history of Hodgkin lymphoma, history of infection with the Epstein-Barr virus, use of immunosuppressive medications, or HIV infection, while some causes are still unknown. The stage of Hodgkin lymphoma can vary at diagnosis and throughout treatment. Stages of Hodgkin’s lymphoma include I, II, III, IV. 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 MMAE?

  • MMAE stands for monomethyl auristatin E
  • Once inside the lymphoma cell, MMAE interferes with the microtubule network, which causes the cancer cell to stop dividing and then die

What does Cure mean?

The word “cure” means there are no cancer cells left in the body and cancer will never come back. Depending on the cancer type and stage, this may be the true goal of therapy. However, it is very difficult to prove all cancer cells are gone. Even though images, like X-rays and MRI’s, and blood tests may not show any signs of cancer, there can be a small amount of cancer cells still left in the body. Because of this, the word “remission” is used more often. This means there are no signs or symptoms of cancer. Patients in remission are followed closely for any signs of cancer returning. Sometimes, more chemotherapy may be given while in remission to prevent the cancer from coming back.

Doctors usually do not consider a patient “cured” until the chance of cancer returning is extremely low. If cancer does return, it usually happens within 5 years of having a remission. Because of this, doctors do not consider a patient cured unless the cancer has not come back within 5 years of remission. The five-year cutoff does not apply to all cancers.

Common AAVD chemotherapy starting doses

  • Brentuximab vedotin 1.2 mg/kg intravenous (I.V) infusion, usually given over 30 minutes on Days 1 and 15 within 1 hour after completion of doxorubicin, vinblastine, and dacarbazine
  • Doxorubicin 25 mg/m2 I.V push or infusion, usually given over 15 minutes on Days 1 and 15
  • Vinblastine 6 mg/m2 I.V. infusion, usually given over 5 to 10 minutes on Days 1 and 15
  • Dacarbazine 375 mg/m2 I.V. infusion, usually given over 30 minutes on Days 1 and 15

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