Is your classical Hodgkin lymphoma (chl) currently in relapse or progressing? An important guide for you

Transcription

1 Is your classical Hodgkin lymphoma (chl) currently in relapse or progressing? An important guide for you

2 Look forward with ADCETRIS (brentuximab vedotin) ADCETRIS is approved for the treatment of adult patients with classical Hodgkin lymphoma (chl) after a stem cell transplant (SCT) fails or after at least 2 combination chemotherapy treatments fail and SCT is not an option. Important Safety Information BOXED WARNING PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): Patients who are treated with ADCETRIS can have a rare, serious infection of the brain called PML. It can cause death. Please see Important Safety Information, including BOXED WARNING, on pages 5-6 and full Prescribing Information attached or at adcetris.com

3 What do I need to know about my therapy options with ADCETRIS (brentuximab vedotin)? Coping with chl that comes back after therapy can be difficult. Fortunately, today there may be different therapy options that can help. ADCETRIS was approved in 2011 to treat adults with relapsed classical Hodgkin lymphoma (chl) who have experienced multiple treatment failures. ADCETRIS can also result in side effects, some of them serious. Please see pages 5-6, 10, and of this brochure and read the full Prescribing Information, including BOXED WARNING, for more information on side effects. What is the most serious safety information I should know about ADCETRIS? PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): Patients who are treated with ADCETRIS can have a rare, serious infection of the brain called PML. It can cause death. Symptoms started at different times after starting ADCETRIS treatment, some within 3 months after the first dose. Other possible causes of PML are prior treatments or diseases that weakened the patient s immune system. Tell your doctor right away if you notice, or anyone close to you notices, the following signs or symptoms: changes in mood or usual behavior; confusion, problems in thinking, or loss of memory; changes in vision, speech, or walking; or decreased strength or weakness on one side of the body. What other therapies should I avoid with ADCETRIS? You should not receive ADCETRIS if you are currently receiving bleomycin because of possible side effects in the lungs. Please talk to your doctor about all the medications you are taking prior to beginning your ADCETRIS therapy. IMPORTANT TERMS Relapse When disease returns after a period of remission, this is called a relapse or a recurrence. Classical Hodgkin lymphoma (chl) The most common type of Hodgkin lymphoma; a blood cancer caused by abnormal growth of a type of white blood cell called a lymphocyte. Stem cell transplant (SCT) A procedure in which treated blood-forming stem cells taken from your own marrow are given back to you after high doses of chemotherapy. Please see Important Safety Information, including BOXED WARNING, on pages 5-6 and full Prescribing Information attached or at adcetris.com 3

4 ADCETRIS may be an option to treat your classical Hodgkin lymphoma (chl) ADCETRIS is FDA approved for the treatment of adult patients with: chl who relapse after an SCT chl who cannot have an SCT and at least 2 combinations of chemotherapy treatments have not worked ADCETRIS TREATMENT IN ADULTS WITH RELAPSED chl SCT Yes Relapsed disease Second-line chemotherapy Is SCT an option? Relapse* No 2 combo-chemotherapy failures ADCETRIS treatment *People who relapse after an SCT can receive other therapies before starting ADCETRIS treatment. 4 ADCETRIS treatment

5 Important Safety Information What is the most important serious safety information I should know about ADCETRIS? PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): Patients who are treated with ADCETRIS can have a rare, serious infection of the brain called PML. It can cause death. Symptoms started at different times after starting ADCETRIS treatment, some within 3 months after the first dose. Other possible causes of PML are prior treatments or diseases that weakened the patient s immune system. ADCETRIS should not be taken with bleomycin because of possible side effects in the lungs. What are the other possible serious side effects of ADCETRIS? Nerve damage: Peripheral neuropathy (nerve damage) that mostly involves numbness or tingling in the hands or feet (sensory) and/or weakness in the arms or legs (motor). Symptoms increase with more doses. Your doctor may change or stop your ADCETRIS dose depending on the severity of your symptoms. Allergic and infusion reactions: Allergic reactions, including severe forms, during infusion or up to 24 hours after administration of ADCETRIS. Patients who had a reaction with earlier doses should receive premedication with later doses, which may include acetaminophen, an antihistamine, and a corticosteroid. Blood problems: Serious cases, including deaths, of fever with a low number of white blood cells have occurred with ADCETRIS. ADCETRIS may also cause a low number of white blood cells lasting a week or more, with or without fever. A low number of platelets (which help the blood clot) or red blood cells has also occurred with ADCETRIS. Your doctor will give you a medicine called growth factor starting with your first dose if you are receiving ADCETRIS in combination with chemotherapy to treat Stage 3 or 4 chl or PTCL. Growth factor is meant to prevent you from having a low number of white blood cells. Your blood counts will be checked before each dose, more often if necessary. You will be monitored for fever. If your white blood cell count is too low, your doctor may delay your next infusion, lower your dose, stop your ADCETRIS therapy, or give you growth factor with future doses of ADCETRIS. Infections: Serious infections, including deaths, that occur when your immune system is weakened, such as pneumonia, bacteremia, and sepsis or septic shock. Tumor lysis syndrome (TLS): You will be closely monitored for TLS if you have a tumor that grows quickly or have many tumor cells throughout your body. Patients with severe kidney disease may have more side effects and deaths compared to patients with normal kidney function and should avoid use of ADCETRIS. Patients with moderate or severe liver disease may have more side effects and deaths compared to patients with normal liver function and should avoid use of ADCETRIS. Liver injury: Serious liver problems, including deaths, have been reported after the first dose of ADCETRIS and after ADCETRIS was stopped and restarted. Your liver function will be monitored. Having liver problems, raised liver enzymes, and some medicines may increase the risk. Your doctor may delay your next infusion, lower your dose, or stop your ADCETRIS therapy if you have liver problems. Lung problems: Serious lung problems, including deaths, have been reported. If you have symptoms, your doctor may hold your ADCETRIS therapy until they improve. Skin problems: Rare but serious skin conditions, including deaths, called Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). If either occurs, your doctor will stop ADCETRIS and treat you for symptoms. Please see full Prescribing Information, including BOXED WARNING, attached or at adcetris.com 5

6 Gastrointestinal (GI) problems: Serious problems, including deaths, related to the pancreas, stomach, intestine, and colon have been reported. Lymphoma that involves the stomach or intestine may increase the risk of GI perforation (hole in the stomach or intestine). Fetal harm: ADCETRIS can harm a fetus (unborn baby). Women should not become pregnant while taking ADCETRIS and for at least 6 months after the last dose of ADCETRIS. What were the most common side effects in clinical trials? 1269 patients were treated with ADCETRIS in clinical trials (used with chemotherapy, or on its own). The most common side effects in any study were nerve damage (peripheral neuropathy) that mostly involves numbness or tingling in the hands or feet (sensory) and/or weakness in the arms or legs (motor), feeling tired, nausea, diarrhea, a low number of white blood cells, infection of the nose or sinuses, fever, constipation, vomiting, hair loss, weight loss, upper stomach pain, a low number of red blood cells, sores or swelling in the mouth, a low number of lymphocytes (a type of white blood cell), and sores or swelling in the digestive tract. What should I tell my doctor before I start treatment with ADCETRIS? Tell your doctor about all of your medical conditions. ADCETRIS should be avoided if you have severe kidney disease or moderate or severe liver disease. Tell your doctor about any medicine you are taking (including over-the-counter drugs, vitamins, and herbal supplements) because it is possible for ADCETRIS to interact with certain types of drugs. Tell your doctor if you are pregnant or plan to become pregnant. You should not take ADCETRIS while pregnant or breastfeeding. Women should use effective birth control while taking ADCETRIS and for at least 6 months after the final dose of ADCETRIS. Men with female partners should use effective birth control while taking ADCETRIS and for at least 6 months after the final dose of ADCETRIS. Contact your doctor if you experience any of the following: Symptoms of nerve damage: Tingling, burning, or numbness in the hands or feet. Changes in sense of touch or trouble moving the hands or feet. Symptoms of infection: Fever of F or higher, chills, cough, or pain upon urination. Symptoms of infusion reaction: Fever, chills, rash, or breathing problems within 24 hours of infusion. Symptoms of liver injury: Fatigue, anorexia, upper stomach pain, dark urine, yellowing of the skin and eyes (jaundice). Symptoms of PML: Changes in mood or usual behavior. Confusion, thinking problems, or loss of memory. Changes in vision, speech, or walking. Decreased strength or weakness on one side of the body. Symptoms of lung problems: New or worsening cough or shortness of breath. Symptoms of acute pancreatitis: Severe abdominal pain. Symptoms of GI problems: Severe stomach pain, chills, fever, nausea, vomiting, or diarrhea. Pregnancy: Pregnant or breastfeeding women should not receive ADCETRIS. ADCETRIS can harm a fetus (unborn baby). Any other side effects that are bothersome or do not go away. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit Safety/MedWatch or call FDA Please see full Prescribing Information, including BOXED WARNING, attached or at adcetris.com 6

7 What are the differences between ADCETRIS (brentuximab vedotin) and chemotherapy? ADCETRIS is not a chemotherapy. It is designed to work differently from standard therapy. ADCETRIS finds and destroys cells that have a protein on their surface called CD30. CD30 is found on chl cells and not commonly found on healthy cells. Even though ADCETRIS is a CD30-directed therapy, it can still harm normal cells and cause side effects. More information on side effects with ADCETRIS therapy can be found on pages 5-6, 10, and and should be discussed with your doctor. Please also read the accompanying full Prescribing Information, including BOXED WARNING, for a complete list of side effects. What type of drug is ADCETRIS? ADCETRIS IS AN ANTIBODY-DRUG CONJUGATE (ADC) An ADC is made up of 3 parts An antibody that finds CD30, a protein on the surface of certain cells. 2 A drug that is designed to cause cell death. 3 A linker that attaches the drug to the antibody and then releases the drug inside the cell. 1 IMPORTANT TERMS Antibody Antibodies are proteins most commonly made by the body s immune system. The antibody that makes up ADCETRIS is synthetically engineered. Please see Important Safety Information, including BOXED WARNING, on pages 5-6 and full Prescribing Information attached or at adcetris.com 7

8 How does ADCETRIS work? CD30 protein ADCETRIS finds cells that have CD30 and enters those cells. Cell with CD30 CD30 protein The linker of ADCETRIS is designed to release the drug after it is inside the cell with CD30. Antibody Released drug Once the drug is released, it disrupts the cell s ability to grow and divide and the cell dies. Cell death 8

9 What were the study results? ADCETRIS (brentuximab vedotin) was studied in 102 adults with chl that had relapsed after an SCT. 73% of people had their tumor shrink by half or more (complete remission + partial remission). 73 %* of people had their tumor shrink by half or more (CR + PR) 32 % of people Complete remission (CR) No detectable tumor remains 40 % of people Partial remission (PR) Less than or equal to 50% of tumor remaining * Percentage are rounded to whole numbers. 32.5% of people had CR and 40.5% of people had PR: CR (32.5%) + PR (40.5%) = 73%. How long did these responses last? In the relapsed chl study, people had responses to therapy that lasted on average: 20.5 months in people who achieved complete remission 3.5 months in people who achieved partial remission IMPORTANT TERMS Complete remission (CR) When cancer can no longer be detected, the person is said to be in complete remission. Partial remission (PR) When therapy has greatly improved the condition but some evidence of the tumor remains, the person is said to have achieved partial remission. Please see Important Safety Information, including BOXED WARNING, on pages 5-6 and full Prescribing Information attached or at adcetris.com 9

10 What were the side effects in the study? The most common side effects reported in the relapsed chl study with 102 people are listed below. MOST COMMON SIDE EFFECTS Neutropenia Reduced number of the white blood cells that help the body defend against infection Fever Peripheral sensory neuropathy Tingling or numbness in the hands or feet Thrombocytopenia Reduced number of platelets in the blood, which help the blood to clot Tiredness Rash Upper respiratory tract infection eg, head colds, sinus, and throat infections Abdominal pain Nausea or upset stomach Cough Diarrhea Vomiting Anemia Reduced number of red blood cells MOST COMMON SERIOUS SIDE EFFECTS Peripheral motor neuropathy Weakness in the hands or feet Collapsed lung Stomach pain Kidney infections Blood clots in the lungs Fever Inflamed lungs The list on this page does not include all of the possible side effects of ADCETRIS therapy. Please read Important Safety Information, including BOXED WARNING, on pages 5-6 and read accompanying full Prescribing Information or visit adcetris.com for more information about possible side effects. Go to pages to read more about side effects with ADCETRIS and how your doctor may be able to manage some of them. 10

11 How is ADCETRIS (brentuximab vedotin) given for relapsed chl? IV infusion 30 minutes Every 3 weeks 3 weeks ADCETRIS is given as an intravenous infusion. Each infusion takes about 30 minutes, and is given every 3 weeks. You will get your ADCETRIS infusion at a doctor s office or clinic. The dose of ADCETRIS is calculated based on your weight. If you have mild liver disease, your doctor may give you a smaller dose of ADCETRIS. People with moderate or severe liver disease or severe kidney disease should avoid using ADCETRIS. How long will I keep taking ADCETRIS? ADCETRIS may be given until disease progresses, relapses, or there are side effects that outweigh the potential benefits of therapy In the relapsed chl study, people received ADCETRIS for up to 1 year (The average length of therapy was 9 cycles) If you continue to respond well and tolerate ADCETRIS therapy, you may continue therapy beyond 1 year Work with your doctor to decide what your therapy plan is and be sure to always discuss changes in your therapy if they occur If ADCETRIS is working for you, your doctor may have you continue therapy as long as side effects remain manageable. Please see Important Safety Information, including BOXED WARNING, on pages 5-6 and full Prescribing Information attached or at adcetris.com 11

12 Why might my doctor change or stop my ADCETRIS therapy? Side effects sometimes cause people to stop therapy earlier than planned. Your doctor might need to delay giving you the next dose or give you a smaller dose of ADCETRIS (brentuximab vedotin) until your symptoms improve. In cases where side effects are severe, or do not improve, you might need to stop taking ADCETRIS completely. It is important to tell your healthcare team as soon as possible about any symptoms that develop. Dose delay Dose reduction Stop therapy In a study of 102 people treated with ADCETRIS, 20% of people stopped therapy with ADCETRIS because of side effects. Adverse reactions that led to stopping therapy in 2 or more people in this study were peripheral sensory neuropathy (6%) and peripheral motor neuropathy (3%). Adverse reactions that led to dose delays in more than 5% of people in this study were neutropenia (16%) and peripheral sensory neuropathy (13%). You can find more information about managing certain side effects on pages of this brochure. 12

13 What do I need to know about ADCETRIS (brentuximab vedotin) and peripheral neuropathy (PN)? Across four studies in which 393 people were treated with ADCETRIS alone, 62% of people experienced mild to severe PN. This includes patients in the relapsed chl study. Please see the tables below for more detailed information. PERIPHERAL SENSORY NEUROPATHY* Mild or Moderate 44% of people experienced mild or moderate peripheral sensory neuropathy This means a feeling of numbness, tingling, pricking, discomfort, burning, or coldness in the skin of the hands or feet. While mild symptoms do not interfere with daily activities, moderate symptoms may limit instrumental daily activities like preparing meals, shopping, and using the telephone Severe 8% of people had severe peripheral sensory neuropathy This means symptoms made certain daily activities difficult. Severe symptoms may limit self-care activities such as bathing, dressing, feeding self, and taking medications PERIPHERAL MOTOR NEUROPATHY* Mild or Moderate 12% of people experienced mild or moderate peripheral motor neuropathy This means weakness in the hands, feet, arms, or legs that may interfere with instrumental daily activities in moderate cases Severe 4% of people had severe peripheral motor neuropathy This means symptoms that made activities such as walking difficult enough that people might require assistance (eg, a cane) *No one experienced symptoms so severe that the condition was life-threatening or disabling. Download a PN Symptom Tracker at adcetris.com to help monitor your symptoms while on ADCETRIS therapy. Please see Important Safety Information, including BOXED WARNING, on pages 5-6 and full Prescribing Information attached or at adcetris.com 13

14 What should I do if I get PN? You can help your doctor by reporting signs of PN if they occur. Your doctor should check regularly for these signs. WHAT ARE THE SYMPTOMS OF PN? Hypoesthesia numbness or decreased sense of touch Discomfort Hyperesthesia increased sense of touch Neuropathic pain (nerve pain) A burning sensation Paresthesia sense of prickling, tingling, or creeping on the skin with no clear cause Weakness Working with your doctor to manage side effect symptoms when they appear may help you maintain therapy consistent with your treatment plan. Your doctor may be able to manage your PN by delaying doses or by giving you less ADCETRIS with each therapy If your symptoms do not get better or get worse, you may need to stop taking ADCETRIS PN with ADCETRIS is cumulative, so it may worsen as therapy continues. During therapy it is important to watch for small changes in feeling or function that might be symptoms of PN. Tell your healthcare team about these right away. IN STUDIES WHERE ADCETRIS WAS USED BY ITSELF Most people who had 62% HAD PN PN found that their PN went away or improved over time. 62% Went away completely 24% Some improvement 38% NO PN Download a PN Symptom Tracker at adcetris.com to help monitor your symptoms while on ADCETRIS therapy % No improvement

15 What do I need to know about ADCETRIS (brentuximab vedotin) and neutropenia? Therapy with ADCETRIS has been shown to cause a side effect called neutropenia. Neutropenia means a decreased number of neutrophils in the blood. ADCETRIS can result in severe neutropenia that may last a week or more. Neutropenia can make it harder for the body to fight infection. Your healthcare team will do regular blood tests to monitor for neutropenia before every dose and will monitor even more often in severe cases. If you experience neutropenia, you should watch for symptoms such as fever, signs of illness, or unusual pain or redness around skin wounds as this could be a sign of a potentially life-threatening infection. Of the 102 people receiving ADCETRIS in the relapsed chl study, 54% experienced neutropenia. Your doctor may delay or reduce your next dose of ADCETRIS or stop therapy, depending on the severity of your neutropenia. There are also other medicines that can be given to help raise a person s neutrophil count. NEUTROPENIA IN THE STUDY OF ADCETRIS IN RELAPSED chl 46% None 33% Mild or moderate Minimal or moderate risk of infection. 15% Severe Severe risk of infection due to insufficient neutrophils. 6% Life-threatening Life-threatening risk of infection due to insufficient neutrophils. Numbers from the study with 102 people with relapsed chl. Neutropenia led to dose delays in 16% of people in the relapsed chl study. IMPORTANT TERMS Neutropenia A reduction in the number of a certain type of white blood cell called a neutrophil. Neutropenia is a common side effect of cancer therapies, including ADCETRIS. Neutrophils are important for helping the body fight infection. Neutropenia increases the risk of infection due to a neutrophil count that is lower than normal. People with a very low neutrophil count may be given a medicine called a growth factor to increase the number of white cells in their blood. Please see Important Safety Information, including BOXED WARNING, on pages 5-6 and full Prescribing Information attached or at adcetris.com 15

16 How does ADCETRIS affect reproductive health? As ADCETRIS is used to treat relapsed chl, which often affects young adults, many people have questions about how ADCETRIS will affect their reproductive health. ADCETRIS can harm a fetus (unborn baby). Women should not become pregnant while taking ADCETRIS and for at least 6 months after the last dose of ADCETRIS. Men with female partners should use effective birth control while taking ADCETRIS and for at least 6 months after the last dose of ADCETRIS. Can I nurse while taking ADCETRIS? You should not breastfeed while taking ADCETRIS. If nursing infants were to receive ADCETRIS in breast milk, it could possibly cause them harm. 16

17 When should I call my doctor? Call your doctor if you experience any of the following: Tingling, burning, or numbness in the hands or feet; changes in sense of touch; or trouble moving the hands or feet; the doctor may change your dose or discontinue ADCETRIS to reduce problems like these A fever of F or higher or chills, a cough, or pain when urinating Fever, chills, a rash, or breathing problems within 24 hours of an ADCETRIS infusion Tiredness (fatigue), loss of appetite, right upper stomach pain, dark urine, or yellowing of the skin and eyes (jaundice) these might be signs or symptoms of liver injury Changes in mood or usual behavior; confusion, thinking problems, or loss of memory; changes in vision, speech, or walking; or decreased strength or weakness on one side of the body these may be signs or symptoms of a serious side effect New or worsening signs of lung problems, such as cough, shortness of breath Severe abdominal pain, which may be a sign of sudden inflammation in the pancreas, known as acute pancreatitis. Gastrointestinal (GI) problems such as severe stomach pain, chills, fever, nausea, vomiting, or diarrhea. You or your partner become pregnant or are planning on becoming pregnant while receiving ADCETRIS or within 6 months after last dose. Women should not take ADCETRIS while pregnant or breastfeeding. ADCETRIS can harm a fetus (unborn baby). Any other side effects that are bothersome or do not go away Any suspected side effects should be reported to Seattle Genetics, Inc. at , or the FDA at 800.FDA.1088 or Please see Important Safety Information, including BOXED WARNING, on pages 5-6 and full Prescribing Information attached or at adcetris.com 17

18 How can I find more information about chl and living with cancer? Here are some websites and organizations that may be useful to you as you learn more about your condition and treatment. You can Connect with other people and their caregivers Available at Hodgkin s Disease Refractory and Relapsed Facebook group facebook.com/groups/ Hodgkin s Lymphoma Caregivers Facebook group facebook.com/groups/ Leukemia & Lymphoma Society lls.org/support-resources Smart Patients smartpatients.com Stupid Cancer Community stupidcancer.org/community Cancer Support Community cancersupportcommunity.org/mainmenu/family-friends Find family support and assistance Caregiver Action Network caregiveraction.com Kids Konnected kidskonnected.org Fertile Action fertileaction.org Learn about fertility issues associated with cancer treatments Save My Fertility savemyfertility.org 18

19 If you have questions about ADCETRIS (brentuximab vedotin) treatment costs, SeaGen Secure may be able to help. See back cover to learn more. You can Get support for employment issues Available at Cancer and Careers cancerandcareers.org National Coalition for Cancer Survivorship canceradvocacy.org Learn about wellness during and after therapy Cancer care and nutrition cancer.net/navigating-cancer-care Learn about managing different aspects of cancer and treatment lls.org/managing-your-cancer Get help with costs related to your therapy CancerCare cancercare.org Cancer Financial Assistance Coalition cancerfac.org Lymphoma Research Foundation lymphoma.org/financialassistanceprograms Seattle Genetics, Inc. is not affiliated with the organizations listed. The listing of independent organizations is provided solely as a reference and is meant for informational purposes only. The listing does not and is not meant to replace a physician s medical advice. Please see Important Safety Information, including BOXED WARNING, on pages 5-6 and full Prescribing Information attached or at adcetris.com 19

20 Enroll in SeaGen Secure personalized support program If you have questions about ADCETRIS (brentuximab vedotin) treatment costs, SeaGen Secure may be able to help. Call SeaGen Secure at 855.4SECURE ( ) to speak with an Oncology Nurse Advocate who can help if you: NO INSURANCE Don t have health insurance UNSURE OF COVERAGE Aren t sure if your insurance will cover ADCETRIS treatment NOT ENOUGH COVERAGE Have insurance that only covers a small amount of your ADCETRIS costs, leaving you with a high balance to pay Talk to your doctor about enrolling in SeaGen Secure or call 855.4SECURE ( ) to learn more Seattle Genetics does not guarantee that enrollment in SeaGen Secure will result in coverage and/or reimbursement. ADCETRIS and its logo, SeaGen Secure and its logo, and Seattle Genetics and, are US registered trademarks of Seattle Genetics, Inc Seattle Genetics, Inc., Bothell, WA All rights reserved US-BVP PR

21 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use ADCETRIS safely and effectively. See full prescribing information for ADCETRIS. ADCETRIS (brentuximab vedotin) for injection, for intravenous use Initial U.S. approval: 2011 WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) See full prescribing information for complete boxed warning. JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS (5.9, 6.1). RECENT MAJOR CHANGES Indications and Usage (1.1, 1.4) 11/2018 Dosage and Administration (2.1, 2.2, 2.3) 11/2018 Dosage and Administration (2.1, 2.2) 03/2018 Warnings and Precautions, Hematologic Toxicities (5.3) 03/2018 INDICATIONS AND USAGE ADCETRIS is a CD30-directed antibody-drug conjugate indicated for treatment of adult patients with: Previously untreated Stage III or IV classical Hodgkin lymphoma (chl), in combination with doxorubicin, vinblastine, and dacarbazine (1.1). Classical Hodgkin lymphoma (chl) at high risk of relapse or progression as postautologous hematopoietic stem cell transplantation (auto-hsct) consolidation (1.2). Classical Hodgkin lymphoma (chl) after failure of auto-hsct or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-hsct candidates (1.3). Previously untreated systemic anaplastic large cell lymphoma (salcl) or other CD30- expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone (1.4) Systemic anaplastic large cell lymphoma (salcl) after failure of at least one prior multiagent chemotherapy regimen (1.5). Primary cutaneous anaplastic large cell lymphoma (pcalcl) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy (1.6). DOSAGE AND ADMINISTRATION Administer only as an intravenous infusion over 30 minutes (2.1). The recommended dose as monotherapy is 1.8 mg/kg up to a maximum of 180 mg every 3 weeks (2.1). The recommended dose in combination with chemotherapy for previously untreated Stage III or IV chl is 1.2 mg/kg up to a maximum of 120 mg every 2 weeks for a maximum of 12 doses (2.1). FULL PRESCRIBING INFORMATION: CONTENTS* WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) 1 INDICATIONS AND USAGE 1.1 Previously untreated Stage III or IV classical Hodgkin lymphoma (chl), in combination with chemotherapy 1.2 Classical Hodgkin lymphoma (chl) consolidation 1.3 Relapsed classical Hodgkin lymphoma (chl) 1.4 Previously untreated systemic anaplastic large cell lymphoma (salcl) or other CD30-expressing peripheral T-cell lymphomas (PTCL), in combination with chemotherapy 1.5 Relapsed systemic anaplastic large cell lymphoma (salcl) 1.6 Relapsed primary cutaneous anaplastic large cell lymphoma (pcalcl) or CD30-expressing mycosis fungoides (MF) 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosage 2.2 Recommended Prophylactic Medications 2.3 Dose Modification 2.4 Instructions for Preparation and Administration 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5.1 Peripheral Neuropathy 5.2 Anaphylaxis and Infusion Reactions 5.3 Hematologic Toxicities 5.4 Serious Infections and Opportunistic Infections 5.5 Tumor Lysis Syndrome 5.6 Increased Toxicity in the Presence of Severe Renal Impairment 5.7 Increased Toxicity in the Presence of Moderate or Severe Hepatic Impairment 5.8 Hepatotoxicity 5.9 Progressive Multifocal Leukoencephalopathy 5.10 Pulmonary Toxicity 5.11 Serious Dermatologic Reactions 5.12 Gastrointestinal Complications 5.13 Embryo-Fetal Toxicity 6 ADVERSE REACTIONS 6.1 Clinical Trial Experience The recommended dose in combination with chemotherapy for previously untreated PTCL is 1.8 mg/kg up to a maximum of 180 mg every 3 weeks for 6 to 8 doses (2.1). Reduce dose in patients with mild hepatic impairment (2.3). DOSAGE FORMS AND STRENGTHS For injection: 50 mg lyophilized powder in a single-dose vial (3). CONTRAINDICATIONS Concomitant use with bleomycin due to pulmonary toxicity (4). WARNINGS AND PRECAUTIONS Peripheral neuropathy: Monitor patients for neuropathy and institute dose modifications accordingly (5.1). Anaphylaxis and infusion reactions: If an infusion reaction occurs, interrupt the infusion. If anaphylaxis occurs, immediately discontinue the infusion (5.2). Hematologic toxicities: Monitor complete blood counts. Monitor for signs of infection. Manage using dose delays and growth factor support (5.3). Serious infections and opportunistic infections: Closely monitor patients for the emergence of bacterial, fungal or viral infections (5.4). Tumor lysis syndrome: Closely monitor patients with rapidly proliferating tumor or high tumor burden (5.5). Hepatotoxicity: Monitor liver enzymes and bilirubin (5.8). Pulmonary toxicity: Monitor patients for new or worsening symptoms (5.10). Serious dermatologic reactions: Discontinue if Stevens-Johnson syndrome or toxic epidermal necrolysis occurs (5.11). Gastrointestinal complications: Monitor patients for new or worsening symptoms (5.12). Embryo-Fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to avoid pregnancy (5.13). ADVERSE REACTIONS The most common adverse reactions ( 20% in any study) were peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, pyrexia, constipation, vomiting, alopecia, decreased weight, abdominal pain, anemia, stomatitis, lymphopenia, and mucositis (6.1). To report SUSPECTED ADVERSE REACTIONS, contact Seattle Genetics, Inc. at or FDA at FDA-1088 or DRUG INTERACTIONS Concomitant use of strong CYP3A4 inhibitors or inducers has the potential to affect the exposure to monomethyl auristatin E (MMAE) (7.1). USE IN SPECIFIC POPULATIONS Moderate or severe hepatic impairment or severe renal impairment: MMAE exposure and adverse reactions are increased. Avoid use (5.6, 5.7, 8.6, 8.7). Lactation: Advise women not to breastfeed (8.2). See 17 for PATIENT COUNSELING INFORMATION. Revised: 11/ Post Marketing Experience 6.3 Immunogenicity 7 DRUG INTERACTIONS 7.1 Effect of Other Drugs on ADCETRIS 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.2 Lactation 8.3 Females and Males of Reproductive Potential 8.4 Pediatric Use 8.5 Geriatric Use 8.6 Renal Impairment 8.7 Hepatic Impairment 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 12.2 Pharmacodynamics 12.3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 14 CLINICAL STUDIES 14.1 Classical Hodgkin Lymphoma 14.2 Systemic Anaplastic Large Cell Lymphoma and Other CD30-Expressing Peripheral T-Cell Lymphomas 14.3 Systemic Anaplastic Large Cell Lymphoma 14.4 Primary Cutaneous Anaplastic Large Cell Lymphoma and CD30-Expressing Mycosis Fungoides 15 REFERENCES 16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied 16.2 Storage 16.3 Special Handling 17 PATIENT COUNSELING INFORMATION *Sections or subsections omitted from the full prescribing information are not listed.

22 FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE 1.1 Previously untreated Stage III or IV classical Hodgkin lymphoma (chl), in combination with chemotherapy ADCETRIS is indicated for the treatment of adult patients with previously untreated Stage III or IV chl, in combination with doxorubicin, vinblastine, and dacarbazine. 1.2 Classical Hodgkin lymphoma (chl) consolidation ADCETRIS is indicated for the treatment of adult patients with chl at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-hsct) consolidation. 1.3 Relapsed classical Hodgkin lymphoma (chl) ADCETRIS is indicated for the treatment of adult patients with chl after failure of auto-hsct or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-hsct candidates. 1.4 Previously untreated systemic anaplastic large cell lymphoma (salcl) or other CD30-expressing peripheral T-cell lymphomas (PTCL), in combination with chemotherapy ADCETRIS is indicated for the treatment of adult patients with previously untreated salcl or other CD30-expressing PTCL, including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone. 1.5 Relapsed systemic anaplastic large cell lymphoma (salcl) ADCETRIS is indicated for the treatment of adult patients with salcl after failure of at least one prior multi-agent chemotherapy regimen. 1.6 Relapsed primary cutaneous anaplastic large cell lymphoma (pcalcl) or CD30-expressing mycosis fungoides (MF) ADCETRIS is indicated for the treatment of adult patients with pcalcl or CD30- expressing MF who have received prior systemic therapy. 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosage The recommended ADCETRIS dosage is provided in Table 1. Administer ADCETRIS as a 30-minute intravenous infusion. The recommended dose for patients with renal or hepatic impairment is provided in Table 2. For dosing instructions of combination agents administered with ADCETRIS, see Clinical Studies (14.1 and 14.2) and the manufacturer s prescribing information. Table 1: WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS [see Warnings and Precautions (5.9), Adverse Reactions (6.1)]. Recommended ADCETRIS Dosage Indication Recommended Dose* Frequency and Duration Previously Untreated Stage III or IV Classical Hodgkin Lymphoma Classical Hodgkin Lymphoma Consolidation Relapsed Classical Hodgkin Lymphoma Previously Untreated Systemic ALCL or Other CD30-expressing Peripheral T-Cell Lymphomas 1.2 mg/kg up to a maximum of 120 mg in combination with chemotherapy 1.8 mg/kg up to a maximum of 180 mg 1.8 mg/kg up to a maximum of 180 mg 1.8 mg/kg up to a maximum of 180 mg in combination with chemotherapy Relapsed Systemic ALCL 1.8 mg/kg up to a maximum of 180 mg Relapsed Primary Cutaneous ALCL or CD30-expressing Mycosis Fungoides 1.8 mg/kg up to a maximum of 180 mg Administer every 2 weeks until a maximum of 12 doses, disease progression, or unacceptable toxicity Initiate ADCETRIS treatment within 4-6 weeks post-auto- HSCT or upon recovery from auto-hsct. Administer every 3 weeks until a maximum of 16 cycles, disease progression, or unacceptable toxicity Administer every 3 weeks until disease progression or unacceptable toxicity Administer every 3 weeks with each cycle of chemotherapy for 6 to 8 doses Administer every 3 weeks until disease progression or unacceptable toxicity Administer every 3 weeks until a maximum of 16 cycles, disease progression, or unacceptable toxicity * The dose for patients weighing greater than 100 kg should be calculated based on a weight of 100 kg Table 2: Recommended Dose for Patients with Renal or Hepatic Impairment Recommended Dose* from Table mg/kg up to a maximum of 120 mg every 2 weeks 1.8 mg/kg up to a maximum of 180 mg every 3 weeks 1.2 mg/kg up to a maximum of 120 mg every 2 weeks 1.8 mg/kg up to a maximum of 180 mg every 3 weeks * The dose for patients weighing greater than 100 kg should be calculated based on a weight of 100 kg. CrCL: creatinine clearance 2.2 Recommended Prophylactic Medications In patients with previously untreated Stage III or IV chl who are treated with ADCETRIS + doxorubicin, vinblastine, and dacarbazine (AVD), administer G-CSF beginning with Cycle 1. In patients with previously untreated PTCL who are treated with ADCETRIS + cyclophosphamide, doxorubicin, and prednisone (CHP), administer G-CSF beginning with Cycle Dose Modification Table 3: Recommended ADCETRIS Dose from Table 1* 1.2 mg/kg up to a maximum of 120 mg every 2 weeks Degree of Impairment Renal Impairment Normal Mild (CrCL greater than ml/min) Moderate (CrCL ml/min) Severe (CrCL less than 30 ml/min) Normal Mild (CrCL greater than ml/min) Moderate (CrCL ml/min) Severe (CrCL less than 30 ml/min) Normal Mild (Child-Pugh A) Hepatic Impairment Moderate (Child-Pugh B) Severe (Child-Pugh C) Normal Mild (Child-Pugh A) Moderate (Child-Pugh B) Severe (Child-Pugh C) Dose Modifications for Peripheral Neuropathy or Neutropenia Monotherapy or Combination Therapy In combination with chemotherapy Severity Peripheral Neuropathy Grade 2 Grade 3 Grade 4 Recommended Dose* 1.2 mg/kg up to a maximum of 120 mg every 2 weeks Avoid use [see Warnings and Precautions (5.6)] 1.8 mg/kg up to a maximum of 180 mg every 3 weeks Avoid use [see Warnings and Precautions (5.6)] 1.2 mg/kg up to a maximum of 120 mg every 2 weeks 0.9 mg/kg up to a maximum of 90 mg every 2 weeks Avoid use [see Warnings and Precautions (5.7)] 1.8 mg/kg up to a maximum of 180 mg every 3 weeks 1.2 mg/kg up to a maximum of 120 mg every 3 weeks Avoid use [see Warnings and Precautions (5.7)] Dose Modification Reduce dose to 0.9 mg/kg up to a maximum of 90 mg every 2 weeks Hold ADCETRIS dosing until improvement to Grade 2 or lower Restart at 0.9 mg/kg up to a maximum of 90 mg every 2 weeks Consider modifying the dose of other neurotoxic chemotherapy agents Discontinue dosing (continued)

23 Table 3: Recommended ADCETRIS Dose from Table 1* 1.8 mg/kg up to a maximum of 180 mg every 3 weeks 1.2 mg/kg up to a maximum of 120 mg every 2 weeks 1.8 mg/kg up to a maximum of 180 mg every 3 weeks 1.8 mg/kg up to a maximum of 180 mg* every 3 weeks Dose Modifications for Peripheral Neuropathy or Neutropenia * The dose for patients weighing greater than 100 kg should be calculated based on a weight of 100 kg 2.4 Instructions for Preparation and Administration Administration Administer ADCETRIS as an intravenous infusion only. Do not mix ADCETRIS with, or administer as an infusion with, other medicinal products. Reconstitution Follow procedures for proper handling and disposal of anticancer drugs [see References (15)]. Use appropriate aseptic technique for reconstitution and preparation of dosing solutions. Determine the number of 50 mg vials needed based on the patient s weight and the prescribed dose [see Dosage and Administration (2.1)]. Reconstitute each 50 mg vial of ADCETRIS with 10.5 ml of Sterile Water for Injection, USP, to yield a single-dose solution containing 5 mg/ml brentuximab vedotin. Direct the stream toward the wall of vial and not directly at the cake or powder. Gently swirl the vial to aid dissolution. DO NOT SHAKE. Inspect the reconstituted solution for particulates and discoloration. The reconstituted solution should be clear to slightly opalescent, colorless, and free of visible particulates. Following reconstitution, dilute immediately into an infusion bag. If not diluted immediately, store the solution at 2 8 C (36 46 F) and use within 24 hours of reconstitution. DO NOT FREEZE. Discard any unused portion left in the vial. Dilution Monotherapy or Combination Therapy As monotherapy In combination with chemotherapy In combination with chemotherapy In combination with chemotherapy Severity New or worsening Grade 2 or 3 Grade 4 Grade 2 Grade 3 Grade 4 Neutropenia Grade 3 or 4 Grade 3 or 4 Dose Modification Hold dosing until improvement to baseline or Grade 1 Restart at 1.2 mg/kg up to a maximum of 120 mg every 3 weeks Discontinue dosing Sensory neuropathy: Continue treatment at same dose Motor neuropathy: Reduce dose to 1.2 mg/kg up to a maximum of 120 mg every 3 weeks Sensory neuropathy: Reduce dose to 1.2 mg/kg, up to a maximum of 120 mg every 3 weeks Motor neuropathy: Discontinue dosing Discontinue dosing Administer G-CSF prophylaxis for subsequent cycles for patients not receiving primary G-CSF prophylaxis Administer G-CSF prophylaxis in subsequent cycles for patients not receiving primary G-CSF As monotherapy Grade 3 or 4 Hold dosing until improvement to baseline or Grade 2 or lower Recurrent Grade 4 despite G-CSF prophylaxis Consider G-CSF prophylaxis for subsequent cycles Consider discontinuation or dose reduction to 1.2 mg/kg up to a maximum of 120 mg every 3 weeks Calculate the required volume of 5 mg/ml reconstituted ADCETRIS solution needed. Withdraw this amount from the vial and immediately add it to an infusion bag containing a minimum volume of 100 ml of 0.9% Sodium Chloride Injection, 5% Dextrose Injection or Lactated Ringer s Injection to achieve a final concentration of 0.4 mg/ml to 1.8 mg/ml brentuximab vedotin. Gently invert the bag to mix the solution. Following dilution, infuse the ADCETRIS solution immediately. If not used immediately, store the solution at 2 8 C (36 46 F) and use within 24 hours of reconstitution. DO NOT FREEZE. 3 DOSAGE FORMS AND STRENGTHS For injection: 50 mg of brentuximab vedotin as a sterile, white to off-white lyophilized, preservative-free cake or powder in a single-dose vial for reconstitution. 4 CONTRAINDICATIONS ADCETRIS is contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation) [see Adverse Reactions (6.1)]. 5 WARNINGS AND PRECAUTIONS 5.1 Peripheral Neuropathy ADCETRIS treatment causes a peripheral neuropathy that is predominantly sensory. Cases of peripheral motor neuropathy have also been reported. ADCETRIS-induced peripheral neuropathy is cumulative. In studies of ADCETRIS as monotherapy, 62% of patients experienced any grade of neuropathy. The median time to onset of any grade was 3 months (range, 0 12). Of the patients who experienced neuropathy, 62% had complete resolution, 24% had partial improvement, and 14% had no improvement at the time of their last evaluation. The median time from onset to resolution or improvement of any grade was 5 months (range, 0 45). Of the patients who reported neuropathy, 38% had residual neuropathy at the time of their last evaluation [Grade 1 (27%), Grade 2 (9%), Grade 3 (2%)]. In ECHELON-1 (Study 5), 67% of patients treated with ADCETRIS + AVD experienced any grade of neuropathy. The median time to onset of any grade was 2 months (range, 0 7), of Grade 2 was 3 months (range, 0 6) and of Grade 3 was 4 months (range, <1 7). The median time from onset to resolution or improvement of any grade was 2 months (range, 0 32), of Grade 2 was 3 months (range, 0 28), and of Grade 3 was 4 months (range, 0 32). Of these patients, 43% had complete resolution, 24% had partial improvement (a decrease in severity by one or more grades from worst grade), and 33% had no improvement at the time of their last evaluation. Of the patients with residual neuropathy at the time of their last evaluation (57%), patients had Grade 1 (36%), Grade 2 (16%), Grade 3 (4%), or Grade 4 (<1%) neuropathy. In ECHELON-2 (Study 6), 52% of patients treated with ADCETRIS + CHP experienced new or worsening peripheral neuropathy of any grade (by maximum grade, 34% Grade 1, 15% Grade 2, 3% Grade 3, < 1% Grade 4). The peripheral neuropathy was predominantly sensory (94% sensory, 16% motor) and had a median onset time of 2 months (range, <1 5). At last evaluation, 50% had complete resolution of neuropathy, 12% had partial improvement, and 38% had no improvement. The median time to resolution or improvement overall was 4 months (range, 0 45). Of patients with residual neuropathy at their last evaluation, the neuropathy was Grade 1 in 72%, Grade 2 in 25%, and Grade 3 in 3%. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Patients experiencing new or worsening peripheral neuropathy may require a delay, change in dose, or discontinuation of ADCETRIS [see Dosage and Administration (2.3) and Adverse Reactions (6.1)]. 5.2 Anaphylaxis and Infusion Reactions Infusion-related reactions, including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If anaphylaxis occurs, immediately and permanently discontinue administration of ADCETRIS and administer appropriate medical therapy. If an infusion-related reaction occurs, interrupt the infusion and institute appropriate medical management. Patients who have experienced a prior infusion-related reaction should be premedicated for subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid. 5.3 Hematologic Toxicities Fatal and serious cases of febrile neutropenia have been reported with ADCETRIS. Prolonged ( 1 week) severe neutropenia and Grade 3 or Grade 4 thrombocytopenia or anemia can occur with ADCETRIS. Start primary prophylaxis with G-CSF beginning with Cycle 1 for patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III or IV chl or previously untreated PTCL [see Dosage and Administration (2.3) and Adverse Reactions (6.1)]. Monitor complete blood counts prior to each dose of ADCETRIS. Monitor more frequently for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent ADCETRIS doses [see Dosage and Administration (2.2, 2.3)]. 5.4 Serious Infections and Opportunistic Infections Serious infections and opportunistic infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in patients treated with ADCETRIS. Monitor patients closely during treatment for the emergence of possible bacterial, fungal, or viral infections. 5.5 Tumor Lysis Syndrome Patients with rapidly proliferating tumor and high tumor burden may be at increased risk of tumor lysis syndrome. Monitor closely and take appropriate measures.

24 5.6 Increased Toxicity in the Presence of Severe Renal Impairment The frequency of Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment compared to patients with normal renal function. Due to higher MMAE exposure, Grade 3 adverse reactions may be more frequent in patients with severe renal impairment compared to patients with normal renal function. Avoid the use of ADCETRIS in patients with severe renal impairment [creatinine clearance (CrCL) <30 ml/min] [see Use in Specific Populations (8.6)]. 5.7 Increased Toxicity in the Presence of Moderate or Severe Hepatic Impairment The frequency of Grade 3 adverse reactions and deaths was greater in patients with moderate and severe hepatic impairment compared to patients with normal hepatic function. Avoid the use of ADCETRIS in patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment [see Use in Specific Populations (8.7)]. 5.8 Hepatotoxicity Fatal and serious cases of hepatotoxicity have occurred in patients receiving ADCETRIS. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin. Cases have occurred after the first dose of ADCETRIS or after ADCETRIS rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may also increase the risk. Monitor liver enzymes and bilirubin. Patients experiencing new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS. 5.9 Progressive Multifocal Leukoencephalopathy Fatal cases of JC virus infection resulting in PML have been reported in ADCETRIStreated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS therapy, with some cases occurring within 3 months of initial exposure. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider the diagnosis of PML in any patient presenting with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS dosing for any suspected case of PML and discontinue ADCETRIS dosing if a diagnosis of PML is confirmed Pulmonary Toxicity Fatal and serious events of noninfectious pulmonary toxicity including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome (ARDS), have been reported. Monitor patients for signs and symptoms of pulmonary toxicity, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement Serious Dermatologic Reactions Fatal and serious cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical therapy Gastrointestinal Complications Fatal and serious events of acute pancreatitis have been reported. Other fatal and serious gastrointestinal (GI) complications include perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus. Lymphoma with preexisting GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, including severe abdominal pain, perform a prompt diagnostic evaluation and treat appropriately Embryo-Fetal Toxicity Based on the mechanism of action and findings in animals, ADCETRIS can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of ADCETRIS in pregnant women. In animal reproduction studies, brentuximab vedotin caused embryo-fetal toxicities, including significantly decreased embryo viability, and fetal malformations at maternal exposures that were similar to the clinical dose of 1.8 mg/kg every three weeks. Advise females of reproductive potential to avoid pregnancy during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS. Advise a pregnant woman of the potential risk to the fetus [see Use in Specific Populations (8.1, 8.3)]. 6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Peripheral Neuropathy [see Warnings and Precautions (5.1)] Anaphylaxis and Infusion Reactions [see Warnings and Precautions (5.2)] Hematologic Toxicities [see Warnings and Precautions (5.3)] Serious Infections and Opportunistic Infections [see Warnings and Precautions (5.4)] Tumor Lysis Syndrome [see Warnings and Precautions (5.5)] Increased Toxicity in the Presence of Severe Renal Impairment [see Warnings and Precautions (5.6)] Increased Toxicity in the Presence of Moderate or Severe Hepatic Impairment [see Warnings and Precautions (5.7)] Hepatotoxicity [see Warnings and Precautions (5.8)] Progressive Multifocal Leukoencephalopathy [see Warnings and Precautions (5.9)] Pulmonary Toxicity [see Warnings and Precautions (5.10)] Serious Dermatologic Reactions [see Warnings and Precautions (5.11)] Gastrointestinal Complications [see Warnings and Precautions (5.12)] 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data below reflect exposure to ADCETRIS in 931 patients with chl including 662 patients who received ADCETRIS in combination with chemotherapy in a randomized controlled trial, and 269 who received ADCETRIS as monotherapy (167 in a randomized controlled trial and 102 in a single arm trial). Data summarizing ADCETRIS exposure are also provided for 347 patients with T-cell lymphoma, including 223 patients with PTCL who received ADCETRIS in combination with chemotherapy in a randomized, double-blind, controlled trial; 58 patients with salcl who received ADCETRIS monotherapy in a single-arm trial; and 66 patients with pcalcl or CD30-expressing MF who received ADCETRIS monotherapy in a randomized, controlled trial. ADCETRIS was administered intravenously at a dose of either 1.2 mg/kg every 2 weeks in combination with AVD, 1.8 mg/kg every 3 weeks in combination with CHP, or 1.8 mg/kg every 3 weeks as monotherapy. The most common adverse reactions ( 20%) with monotherapy were peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, and pyrexia. The most common adverse reactions ( 20%) in combination with AVD were peripheral neuropathy, neutropenia, nausea, constipation, vomiting, fatigue, diarrhea, pyrexia, alopecia, decreased weight, abdominal pain, anemia, and stomatitis. The most common adverse reactions ( 20%) in combination with CHP were anemia, neutropenia, peripheral neuropathy, lymphopenia, nausea, diarrhea, fatigue or asthenia, mucositis, constipation, alopecia, pyrexia, and vomiting. Previously Untreated Stage III or IV Classical Hodgkin Lymphoma (Study 5: ECHELON-1) ADCETRIS in combination with AVD was evaluated for the treatment of previously untreated patients with Stage III or IV chl in a randomized, open-label, multicenter clinical trial of 1334 patients. Patients were randomized to receive up to 6 cycles of ADCETRIS + AVD or ABVD on Days 1 and 15 of each 28-day cycle. The recommended starting dose of ADCETRIS was 1.2 mg/kg intravenously over 30 minutes, administered approximately 1 hour after completion of AVD therapy. A total of 1321 patients received at least one dose of study treatment (662 ADCETRIS + AVD, 659 ABVD). The median number of treatment cycles in each study arm was 6 (range, 1 6); 76% of patients on the ADCETRIS + AVD arm received 12 doses of ADCETRIS [see Clinical Studies (14.1)]. After 75% of patients had started study treatment, the use of prophylactic G-CSF was recommended with the initiation of treatment for all ADCETRIS + AVD treated patients, based on the observed rates of neutropenia and febrile neutropenia [see Dosage and Administration (2.2)]. Among 579 patients on the ADCETRIS + AVD arm who did not receive G-CSF primary prophylaxis beginning with Cycle 1, 96% experienced neutropenia (21% with Grade 3; 67% with Grade 4), and 21% had febrile neutropenia (14% with Grade 3; 6% with Grade 4). Among 83 patients on the ADCETRIS + AVD arm who received G-CSF primary prophylaxis beginning with Cycle 1, 61% experienced neutropenia (13% with Grade 3; 27% with Grade 4), and 11% experienced febrile neutropenia (8% with Grade 3; 2% with Grade 4). Serious adverse reactions, regardless of causality, were reported in 43% of ADCETRIS + AVD-treated patients and 27% of ABVD-treated patients. The most common serious adverse reactions in ADCETRIS + AVD-treated patients were febrile neutropenia (17%), pyrexia (7%), neutropenia and pneumonia (3% each). Adverse reactions that led to dose delays of one or more drugs in more than 5% of ADCETRIS + AVD-treated patients were neutropenia (21%) and febrile neutropenia (8%) [see Dosage and Administration (2.2)]. Adverse reactions led to treatment discontinuation of one or more drugs in 13% of ADCETRIS + AVD-treated patients. Seven percent of patients treated with ADCETRIS + AVD discontinued due to peripheral neuropathy. There were 9 on-study deaths among ADCETRIS + AVD-treated patients; 7 were associated with neutropenia, and none of these patients had received G-CSF prior to developing neutropenia. Table 4: Adverse Reactions Reported in 10% of ADCETRIS + AVD-Treated Patients in Previously Untreated Stage III or IV Classical Hodgkin Lymphoma (Study 5: ECHELON-1) ADCETRIS + AVD ABVD Total N = 662 Total N = 659 % of patients % of patients Any Grade Grade Any Grade Grade Adverse Reaction Grade 3 4 Grade 3 4 Blood and lymphatic system disorders Anemia* < <1 Neutropenia* Febrile neutropenia (continued)