What to Know About Adcetris (Brentuximab Vedotin)

An Antibody-Drug Conjugate Approved to Treat Several Forms of Lymphoma

In This Article

Adcetris (brentuximab vedotin) is an antibody-drug conjugate recommended for use in more aggressive forms of lymphoma, which are cancers of the body’s lymphatic system, associated with immune response. Administered via intravenous (IV) injection, this medication may sometimes accompany chemotherapy or be indicated as therapy on its own

A man-made antibody that’s been modified to target and kill cancerous lymph cells that contain the protein CD30, this medication’s specific activity makes it a promising targeted therapy. In doing so, it’s able to both prevent the spread of cancer cells and kill them.

Uses

Adcetris is often prescribed after other initial therapies have already been attempted. Specifically, it’s approved for:

  • Stage III or IV classical Hodgkin lymphoma (cHL): Classical Hodgkin lymphoma is the most common form of lymphoma. In these cases, specific cells called B lymphocytes (B cells) are disrupted; these normally help the body form antibodies, which protect from infections. Adcetris is prescribed when this cancer is first discovered in more advanced stages.
  • cHL after autologous hematopoietic cell transplantation (HCT): HCT therapy involves the introduction of stem cells (cells that are undifferentiated and can develop into many different forms) to re-establish bone marrow and immune function. If, following this therapy, there is a risk of relapse of cancer or if it has not succeeded, Adcetris may be prescribed. 
  • cHL after other therapy: If other approaches, such as radiation or chemotherapy, have not been successful in treatment cHL or if there is a relapse, Adcetris is indicated for use.
  • Systemic anaplastic large cell lymphoma (sALCL): sALCL is a rare, aggressive form of non-Hodgkin lymphoma that targets T cells (another essential cell for immune function) as well as B cells. If newly discovered, Adcetris may be prescribed alongside cyclophosphamide, Lipodox (doxorubicin), and Rayos (prednisone) as part of a chemotherapy regimen. It may also be considered after other therapies have not yielded good results.  
  • Primary cutaneous anaplastic large cell lymphoma (pcALCL)/ CD30-expressing mycosis fungoides (MF): Primary cutaneous anaplastic large cell lymphoma primarily appears in the skin and is considered less aggressive than the systemic form. MF is another rare form of lymphoma that targets the body’s t-cells. In both cases, Adcetris is recommended only if prior treatments have not yielded results.    

Before Taking

Given that this drug takes on several forms of lymphoma, proper diagnosis and assessment is necessary before Adcetris can be prescribed. This class of cancer is first detected following physical assessment as well as identification using blood tests and biopsy of the lymph node (in which a small portion is extracted for evaluation).

Following that, the subtype and progression of the disease is evaluated using any number of methods:

  • X-ray
  • Bone marrow biopsy
  • Lumbar puncture
  • Computer tomography (CT scan)
  • Positron emission tomography (PET scan)
  • Bone scan
  • Magnetic resonance imaging (MRI)

This allows the doctor to get a full sense of the type of lymphoma they’re dealing with, as well as how much it has spread. As noted above, Adcetris is not typically a first line treatment and is usually considered either alongside other therapies or if previous approaches have not yielded desired results. 

Precautions and Contraindications

Adcetris and drugs like it can have a range of effects on the body, and some people may not be good candidates for this therapy. Factors that need to be considered include:

  • Bleo 15k (bleomycin) therapy: Most notably, use of this drug is contraindicated for those who are being administered Bleo 15k (bleomycin), a chemotherapy drug, due to potentially adverse effects on the lungs.
  • Presence of peripheral neuropathy: Peripheral neuropathy occurs when the peripheral nervous system—the communication network between body and brain—becomes damaged. Since Adcetris can further such damage or even cause it, it may not be the best approach for those who have this condition or are starting to show signs of it.
  • Severe allergic reaction: Anaphylaxis, a severe allergic reaction, has been known to occur during the administration of this drug. Doctors need to carefully monitor the situation, especially if reactions like this have occurred before, and will discontinue use or augment it with other drugs if this starts to occur.
  • Neutropenia: This condition is characterized by a low number of white blood cells and weakened immune function. It can be a side-effect of a number of cancer medications. The presence of neutropenia may preclude using Adcetris.
  • Opportunistic infections: Given this drug’s effect on the immune system, those who have other viral, bacterial, or fungal infections, such as pneumonia, bacteremia, or sepsis may not be good candidates. Notably, use of Adcetris can contribute to the spread of these diseases, so monitoring for these is standard practice.
  • Liver problems: The liver plays a key role in the processing and breaking down of drugs you take, and an unintended side-effect of Adcetris is that it can harm this organ. This being the case, the presence of liver damage, as in diseases like cirrhosis, may force doctors to reconsider treatment. Monitoring is therefore essential as therapy progresses, and those with serious problems may require an alternative approach.
  • Kidney problems: As with the liver, the presence or history of kidney problems may also be a reason this treatment may not be recommended. Throughout treatment, the doctor will also monitor the health of these essential organs and cease treatment if the damage becomes excessive.
  • Progressive multifocal leukoencephalopathy (PML): A neurological disorder, PML is characterized by the destruction of myelin, a substance that coats and protects nerve and brain cells. Adcetris use itself has been linked with the development of this condition, so doctors need to carefully monitor for it. Particularly, a prior history of taking immunosuppressive drugs or with underlying diseases that lead to PML, may be reasons this therapy should not be attempted.
  • Lung issues: Use of Adcetris has also been known to affect lung function, leading to dangerous and potentially fatal conditions such as pneumonitis (an inflammation of lung tissue), interstitial lung disease (also known as pulmonary fibrosis, this is a scarring and inflammation of the tissue surrounding air sacs, blood vessels, and airways), and acute respiratory distress syndrome (ARDS) (in which fluid fills the lungs). A history of lung problems, then, may be a reason not to take up this therapy.
  • Gastrointestinal conditions: Adverse effects on the gastrointestinal symptom have been reported with Adcetris, leading to quite a few adverse reactions, including acute pancreatitis (inflamed pancreas), intestinal perforations, ulcer, gastrointestinal hemorrhage, intestinal obstruction, and enterocolitis (inflammation of the small intestine and colon), among others. A history of gastrointestinal problems like these may make treatment problematic.
  • Pregnancy: Research on animals has found that the use of Adcetris may potentially cause harm to the developing fetus. As such, pregnant women will be advised of this risk prior to undergoing treatment and may want to consider options. Women should avoid getting pregnant while taking this drug and for at least six months after the final dose.
  • Breastfeeding: Due to potential complications, mothers will be asked to cease breastfeeding during the course of treatment and for up to six months afterward.
  • Age: The safety of Adcetris has not been established for pediatric patients. Those over the age of 65 are also at an increased risk of dangerous side-effects, which may influence therapeutic decision-making.

Other Antibody-Drug Conjugates

Adcetris is just one of the class of antibody-drug conjugates, all of which work the same way: by targeting the CD30 protein found on cancer cells. Currently, seven others are approved by the Food and Drug Administration (FDA) for clinical use:

  • Kadcyla (ado-trastuzumab emtansine)
  • Padcev (enfortumab vedotin)
  • Enhertu (fam-trastuzumab deruxtecan-nxki)
  • Mylotarg (gemtuzumab ozogamicin)
  • Besponsa (inotuzumab ozogamicin) 
  • Polivy (polatuzumab vedotin-piiq)
  • Trodelvy (sacituzumab govitecan-hziy)

Dosage

Adcetris is administered at the hospital via IV injection for 30 minutes at a time; it’s not a pill you can take. The specific dosage depends on the condition being treated and may also be adjusted by your doctor based on your case. Below are FDA recommendations for dosage:

  • Stage III or IV cHL: Alongside chemotherapy, 1.2 milligrams (mg) per kilogram (kg) of bodyweight is recommended, with a maximum of 120 mg per day. Treatments are administered once every two weeks up to 12 times or until toxicity is unacceptable.
  • cHL after HCT: Following HCT, it’s recommended that doctors wait four to six weeks before initiating Adcetris treatment. Dosage in these cases is 1.8 mg per kg for a maximum of 180 mg a day. This should be administered once every three weeks for up to 16 treatments, or until levels of toxicity in the body are unacceptable.    
  • Relapsed cHL: For relapsed cases of cHL, guidelines are similar to cHL after HCT: 1.8 mg per kg of body weight, and no more than 180 mg a day. This is done once every three weeks for a maximum of 16 treatments.
  • Systemic ALCL: For newly-diagnosed systemic ALCL, 1.8 mg per kg of bodyweight is administered, with a daily maximum of 180 mg, alongside chemotherapy. Treatments occur once every three weeks for a maximum six to eight sessions, or until other adverse effects are unbearable.
  • Relapsed pcALCL/CD30-expressing mycosis fungoides: Cases of pcALCL or MF relapse are treated with doses of 1.8mg per kg of body weight administered once every three weeks. This can be done for up to 16 treatments, or until toxicity becomes unbearable.

Keep in mind that the above are recommendations, not prescriptions. Your doctor may need to adjust dosages and schedules based on your health status or other factors.

Modifications

As noted above, dosages of Adcetris are always modified based on bodyweight. In addition, dose strength is modified in the presence of certain conditions:

  • Liver diseases: Doses that are typically 1.2 mg per kg are reduced to 0.9 mg (for a maximum of 90 mg per day) in cases of mild impairment of the liver, and treatment ceases in more severe cases. Cases that would typically require the higher 1.8 mg per kg dose are reduced 1.2 mg in the presence of minor liver damage, with treatment stopped if the liver gets worse.    
  • Peripheral neuropathy: Peripheral neuropathy is broken based on severity, with grade 4 being the most severe and grade 1 being the least. Cases that would typically call for 1.2 mg per kg are reduced to 0.9 mg when you have grade 2 neuropathy, and treatment is stopped in cases of grade 3 or 4. Those that call for 1.8 mg per kg in conjunction with chemotherapy are cut back to 1.2 mg in grade 2 and 3 neuropathy.   
  • Neutropenia: Administration of Adcetris is paused in more severe cases (grades 3 or 4) of neutropenia, and, oftentimes, other drugs need to be coadministered, especially when this drug is taken alongside chemotherapy.

Since this treatment is only administered via IV injection, patients don’t need to worry about storage or safe-disposal.

Side Effects

As with any cancer drug, Adcetris may lead to a range of side-effects, from the more minor to the severe and even deadly. Throughout the course of your treatment, the doctor will be monitoring for any adverse reactions.

Keep track of how you’re feeling, and don't ignore adverse symptoms. If you're feeling sick or if anything seems off, make sure to let your doctor know. Keep in mind: some adverse reactions to this drug constitute medical emergencies.

Common

Side-effects are frequently reported among those taking Adcetris. The most common these are:

  • Fatigue
  • Upper-respiratory infection
  • Nausea
  • Vomiting
  • Diarrhea
  • Anemia (lack of red blood cells in the body)
  • Fever
  • Rash or itchiness
  • Stomach or abdominal pain
  • Cough
  • Fatigue
  • Sudden weight loss
  • Constipation
  • Swollen hands and/or feet
  • Tingling or numbness in hands or feet
  • Dry skin
  • Hair loss
  • Headaches
  • Dizziness
  • Increased anxiety
  • Muscle spasm
  • Muscle or joint pain
  • Night sweats
  • Insomnia
  • Low white blood cell count (neutropenia)
  • Low blood platelet count (thrombocytopenia)

Severe

Adverse reactions to Adcetris are medical emergencies and may require immediate attention. Among the more severe side-effects of this drug are:

  • Infusion-related reactions: In some cases, people may have a severe allergic reaction to Adcetris as it’s being administered. This leads to shortness of breath, lowered blood pressure, chest pains, rash, and itchiness.
  • Liver toxicity: As highlighted above, Adcetris can have a harsh, damaging effect on the liver. This organ’s function is monitored throughout treatment, but signs of a serious problem include yellowing of the skin or eyes (jaundice), dark or brown urine, and abdominal pain.
  • Tumor lysis syndrome: This condition can occur when tumors in the body breakdown quickly and their waste overwhelms the bloodstream. This leads to a range of symptoms, including nausea, vomiting, fatigue, or diarrhea, all of which are reasons to contact your doctor.
  • Stevens-Johnson syndrome: This rare allergic reaction affects the skin and mucous membranes. Potentially fatal, this condition arises as rashes or painful blisters.
  • Gastrointestinal tear/pancreatitis: Tears in the wall of the intestines can occur as a result of this therapy, and this can, in turn, lead to pancreatitis (infection and swelling of the pancreas). These issues are characterized by severe abdominal pain, swelling in the abdomen, chills, fever, constipation, nausea, or vomiting.
  • Cardiac arrhythmia: Irregular heartbeat can also occur as a result of taking this medication. This leads to fatigue, weakness, dizziness, fainting spells, rapid heartbeat, shortness of breath, and chest pain, among other symptoms. 

If you’re feeling any of these symptoms or suspect you have these conditions, be sure to contact your doctor right away or go to the emergency room.

Warnings and Interactions

In terms of pharmacology, adverse interactions and effects have been reported when Adcetris has been taken alongside a class of drugs (and other substances) called CYP3A4 inhibitors. These include:

  • Xolagel (ketoconazole)
  • Norvir (ritonavir)
  • Verelan (verapamil)
  • Erygel (clarithromycin)
  • Erythromycin
  • Tiazac (diltiazem)
  • Goldenseal
  • Grapefruit

It’s always important to track what other drugs or substances you're taking during treatment and let your doctor know. If you plan on making any changes to your regimen or are thinking about taking new supplements or other drugs, be sure to let them know.

Since Adcetris is only administered in the hospital, there are no special considerations needed for ceasing treatment. Your doctor and oncology team will be monitoring your status throughout your course and will let you know if the therapy should change or stop altogether. 

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Article Sources
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