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Adcetris

Adcetris (Brentuximab Vedotin) side effects drug center

 

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CONSUMER

SIDE EFFECTS

 

Adcetris Side Effects Center

What Is Adcetris?

Adcetris (brentuximab vedotin) is an antibody conjugated drug (a combination of three components) indicated for treatment of patients with Hodgkin lymphoma (Hodgkin's disease) and for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL). Adcetris is to be used in patients who have received two prior chemotherapy treatments and cannot receive a transplant. Adcetris may also be used in patients with ALCL whose disease has progressed after one prior chemotherapy treatment.

What Are Side Effects of Adcetris?

Common side effects of Adcetris include:

Tell your doctor if you have any serious side effects, even if they occur several months after you receive Adcetris, or after your treatment with Adcetris ends:

  • weakness, burning pain, or loss of feeling in your arms or legs;
  • chills, body aches, flu symptoms, sores in your mouth and throat;
  • pale skin, lightheadedness, shortness of breath, rapid heart rate, trouble concentrating;
  • easy bruising, unusual bleeding, purple or red pinpoint spots under your skin;
  • lower back pain, blood in your urine;
  • pain or burning when you urinate, urinating less than usual or not at all;
  • numbness or tingling around your mouth;
  • muscle weakness, tightness, or contraction, overactive reflexes;
  • fast or slow heart rate, weak pulse, confusion, fainting; or
  • severe skin reaction -- fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Serious side effects include:

Dosage for Adcetris

Adcetris is available in single–use vials when reconstituted with 10.5 ml of sterile water contain strength of 5 mg per ml brentuximab vedotin. The recommended dose for Adcetris is 1.8 mg/kg administered only as an intravenous infusion over 30 minutes every 3 weeks. Continue treatment until a maximum of 16 cycles, disease progression, or unacceptable toxicity.

Adcetris and Pregnancy

Adcetris can cause fetal harm. Women receiving Adcetris are advised to avoid pregnancy. Women who become pregnant while receiving Adcetris should speak with their doctors immediately. Additionally, patients should be advised to avoid nursing while receiving Adcetris.

Adcetris In Children

Safety and effectiveness has not been established in the pediatric population.

Additional Information

Our Adcetris Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

 

Adcetris Consumer Information

Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning in your eyes, skin pain, red or purple skin rash that spreads and causes blistering and peeling).

Some side effects may occur during the injection or within 24 hours afterward. Tell your caregiver right away if you feel dizzy, nauseated, chilled or feverish, or if you have itching or trouble breathing.

Brentuximab vedotin may cause a serious brain infection that can lead to disability or death. Call your doctor right away if you have problems with speech, thought, vision, or muscle movement. These symptoms may start gradually and get worse quickly.

Also call your doctor if you have any of these other serious side effects, even if they occur several months after you receive brentuximab vedotin:

  • numbness, weakness, burning pain, tingly feeling, or loss of feeling in your arms or legs;
  • sudden chest pain or discomfort, wheezing, dry cough, feeling short of breath;
  • pain or burning when you urinate;
  • high blood sugar--increased thirst, increased urination, dry mouth, fruity breath odor;
  • ketoacidosis (too much acid in the blood)--nausea, vomiting, stomach pain, confusion, unusual drowsiness, or trouble breathing; or
  • low blood cell counts--fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed or short of breath;
  • signs of tumor cell breakdown--confusion, weakness, muscle cramps, nausea, vomiting, fast or slow heart rate, decreased urination, tingling in your hands and feet or around your mouth;
  • pancreatitis--severe pain in your upper stomach spreading to your back, nausea and vomiting;
  • liver problems--loss of appetite, stomach pain (upper right side), tiredness, dark urine, jaundice (yellowing of the skin or eyes); or
  • stomach problems--severe constipation, new or worsening stomach pain, bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds.

Common side effects may include:

  • numbness or tingling;
  • fever;
  • low blood cell counts;
  • nausea, vomiting, diarrhea, constipation; or
  • feeling tired.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Adcetris (Brentuximab Vedotin)

 

Adcetris Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

  • Peripheral Neuropathy [see WARNINGS AND PRECAUTIONS]
  • Anaphylaxis and Infusion Reactions [see WARNINGS AND PRECAUTIONS]
  • Hematologic Toxicities [see WARNINGS AND PRECAUTIONS]
  • Serious Infections and Opportunistic Infections [see WARNINGS AND PRECAUTIONS]
  • Tumor Lysis Syndrome [see WARNINGS AND PRECAUTIONS]
  • Increased Toxicity in the Presence of Severe Renal Impairment [see WARNINGS AND PRECAUTIONS]
  • Increased Toxicity in the Presence of Moderate or Severe Hepatic Impairment [see WARNINGS AND PRECAUTIONS]
  • Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
  • Progressive Multifocal Leukoencephalopathy [see WARNINGS AND PRECAUTIONS]
  • Pulmonary Toxicity [see WARNINGS AND PRECAUTIONS]
  • Serious Dermatologic Reactions [see WARNINGS AND PRECAUTIONS]
  • Gastrointestinal Complications [see WARNINGS AND PRECAUTIONS]
  • Hyperglycemia [see WARNINGS AND PRECAUTIONS]

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].

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]. 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]. 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)

Body System
Adverse Reaction		 ADCETRIS + AVD Total
N = 662 % of patients		 ABVD Total
N = 659 % of patients
Any Grade Grade 3 Grade 4 Any Grade Grade 3 Grade 4
Blood and lymphatic system disorders
Anemia* 98 11 <1 92 6 <1
Neutropenia* 91 20 62 89 31 42
Febrile neutropenia 19 13 6 8 6 2
Gastrointestinal disorders
Constipation 42 2 - 37 <1 <1
Vomiting 33 3 - 28 1 -
Diarrhea 27 3 <1 18 <1 -
Stomatitis 21 2 - 16 <1 -
Abdominal pain 21 3 - 10 <1 -
Nervous system disorders
Peripheral sensory neuropathy 65 10 <1 41 2 -
Peripheral motor neuropathy 11 2 - 4 <1 -
General disorders and administration site conditions
Pyrexia 27 3 <1 22 2 -
Musculoskeletal and connective tissue disorders
Bone pain 19 <1 - 10 <1 -
Back pain 13 <1 - 7 - -
Skin and subcutaneous tissue disorders
Rashes, eruptions and exanthemsa 13 <1 <1 8 <1 -
Respiratory, thoracic and mediastinal disorders
Dyspnea 12 1 - 19 2 -
Investigations
Decreased weight 22 <1 - 6 <1 -
Increased alanine aminotransferase 10 3 - 4 <1 -
Metabolism and nutrition disorders
Decreased appetite 18 <1 - 12 <1 -
Psychiatric disorders
Insomnia 19 <1 - 12 <1 -
* Derived from laboratory values and adverse reaction data; data are included for clinical relevance irrespective of rate between arms
a Grouped term includes rash maculo-papular, rash macular, rash, rash papular, rash generalized, and rash vesicular.
AVD = doxorubicin, vinblastine, and dacarbazine
ABVD = doxorubicin, bleomycin, vinblastine, and dacarbazine
Events were graded using the NCI CTCAE Version 4.03
Events listed are those having a ≥5% difference in rate between treatment arms

Classical Hodgkin Lymphoma Post-Auto-HSCT Consolidation (Study 3: AETHERA)

ADCETRIS was studied in 329 patients with cHL at high risk of relapse or progression post-auto-HSCT in a randomized, double-blind, placebo-controlled clinical trial in which the recommended starting dose and schedule was 1.8 mg/kg of ADCETRIS administered intravenously over 30 minutes every 3 weeks or placebo for up to 16 cycles. Of the 329 enrolled patients, 327 (167 ADCETRIS, 160 placebo) received at least one dose of study treatment. The median number of treatment cycles in each study arm was 15 (range, 1-16) and 80 patients (48%) in the ADCETRIS-treatment arm received 16 cycles [see Clinical Studies].

Standard international guidelines were followed for infection prophylaxis for herpes simplex virus (HSV), varicella-zoster virus (VZV), and Pneumocystis jiroveci pneumonia (PJP) post-auto-HSCT. Overall, 312 patients (95%) received HSV and VZV prophylaxis with a median duration of 11.1 months (range, 0-20) and 319 patients (98%) received PJP prophylaxis with a median duration of 6.5 months (range, 0-20).

Adverse reactions that led to dose delays in more than 5% of ADCETRIS-treated patients were neutropenia (22%), peripheral sensory neuropathy (16%), upper respiratory tract infection (6%), and peripheral motor neuropathy (6%) [see DOSAGE AND ADMINISTRATION]. Adverse reactions led to treatment discontinuation in 32% of ADCETRIS-treated patients. Adverse reactions that led to treatment discontinuation in 2 or more patients were peripheral sensory neuropathy (14%), peripheral motor neuropathy (7%), acute respiratory distress syndrome (1%), paresthesia (1%), and vomiting (1%). Serious adverse reactions were reported in 25% of ADCETRIS-treated patients. The most common serious adverse reactions were pneumonia (4%), pyrexia (4%), vomiting (3%), nausea (2%), hepatotoxicity (2%), and peripheral sensory neuropathy (2%).

Table 5: Adverse Reactions Reported in ≥10% in ADCETRIS-Treated Patients with Classical Hodgkin Lymphoma Post-Auto-HSCT Consolidation (Study 3: AETHERA)

Body System
Adverse Reaction		 ADCETRIS Total
N = 167 % of patients		 Placebo Total
N = 160 % of patients
Any Grade Grade 3 Grade 4 Any Grade Grade 3 Grade 4
Blood and lymphatic system disorders
Neutropenia* 78 30 9 34 6 4
Thrombocytopenia* 41 2 4 20 3 2
Anemia* 27 4 - 19 2 -
Nervous system disorders
Peripheral sensory neuropathy 56 10 - 16 1 -
Peripheral motor neuropathy 23 6 - 2 1 -
Headache 11 2 - 8 1 -
Infections and infestations
Upper respiratory tract infection 26 - - 23 1 -
General disorders and administration site conditions
Fatigue 24 2 - 18 3 -
Pyrexia 19 2 - 16 - -
Chills 10 - - 5 - -
Gastrointestinal disorders
Nausea 22 3 - 8 - -
Diarrhea 20 2 - 10 1 -
Vomiting 16 2 - 7 - -
Abdominal pain 14 2 - 3 - -
Constipation 13 2 - 3 - -
Respiratory, thoracic and mediastinal disorders
Cough 21 - - 16 - -
Dyspnea 13 - - 6 - 1
Investigations
Weight decreased 19 1 - 6 - -
Musculoskeletal and connective tissue disorders
Arthralgia 18 1 - 9 - -
Muscle spasms 11 - - 6 - -
Myalgia 11 1 - 4 - -
Skin and subcutaneous tissue disorders
Pruritus 12 1 - 8 - -
Metabolism and nutrition disorders
Decreased appetite 12 1 - 6 - -
*Derived from laboratory values and adverse reaction data
Events were graded using the NCI CTCAE Version 4

Relapsed Classical Hodgkin Lymphoma (Study 1)

ADCETRIS was studied in 102 patients with cHL in a single arm clinical trial in which the recommended starting dose and schedule was 1.8 mg/kg intravenously every 3 weeks. Median duration of treatment was 9 cycles (range, 1-16) [see Clinical Studies].

Adverse reactions that led to dose delays in more than 5% of ADCETRIS-treated patients were neutropenia (16%) and peripheral sensory neuropathy (13%) [see DOSAGE AND ADMINISTRATION]. Adverse reactions led to treatment discontinuation in 20% of ADCETRIS-treated patients. Adverse reactions that led to treatment discontinuation in 2 or more patients were peripheral sensory neuropathy (6%) and peripheral motor neuropathy (3%). Serious adverse reactions were reported in 25% of ADCETRIS-treated patients. The most common serious adverse reactions were peripheral motor neuropathy (4%), abdominal pain (3%), pulmonary embolism (2%), pneumonitis (2%), pneumothorax (2%), pyelonephritis (2%), and pyrexia (2%).

Table 6: Adverse Reactions Reported in ≥10% of Patients with Relapsed Classical Hodgkin Lymphoma (Study 1)

Body System
Adverse Reaction		 cHL Total
N = 102 % of patients
Any Grade Grade 3 Grade 4
Blood and lymphatic system disorders
Neutropenia* 54 15 6
Anemia* 33 8 2
Thrombocytopenia* 28 7 2
Lymphadenopathy 11 - -
Nervous system disorders
Peripheral sensory neuropathy 52 8 -
Peripheral motor neuropathy 16 4 -
Headache 19 - -
Dizziness 11 - -
General disorders and administration site conditions
Fatigue 49 3 -
Pyrexia 29 2 -
Chills 13 - -
Infections and infestations
Upper respiratory tract infection 47 - -
Gastrointestinal disorders
Nausea 42 - -
Diarrhea 36 1 -
Abdominal pain 25 2 1
Vomiting 22 - -
Constipation 16 - -
Skin and subcutaneous tissue disorders
Rash 27 - -
Pruritus 17 - -
Alopecia 13 - -
Night sweats 12 - -
Respiratory, thoracic and mediastinal disorders
Cough 25 - -
Dyspnea 13 1 -
Oropharyngeal pain 11 - -
Musculoskeletal and connective tissue disorders
Arthralgia 19 - -
Myalgia 17 - -
Back pain 14 - -
Pain in extremity 10 - -
Psychiatric disorders
Insomnia 14 - -
Anxiety 11 2 -
Metabolism and nutrition disorders
Decreased appetite 11 - -
*Derived from laboratory values and adverse reaction data
Events were graded using the NCI CTCAE Version 3.0

Previously Untreated Systemic Anaplastic Large Cell Lymphoma Or Other CD30Expressing Peripheral T-Cell Lymphomas (Study 6, ECHELON-2)

ADCETRIS in combination with CHP was evaluated in patients with previously untreated, CD30expressing PTCL in a multicenter randomized, double-blind, double dummy, actively controlled trial. Patients were randomized to receive ADCETRIS + CHP or CHOP for 6 to 8, 21-day cycles. ADCETRIS was administered on Day 1 of each cycle, with a starting dose of 1.8 mg/kg intravenously over 30 minutes, approximately 1 hour after completion of CHP [see Clinical Studies]. The trial required hepatic transaminases ≤3 times upper limit of normal (ULN), total bilirubin ≤1.5 times ULN, and serum creatinine ≤2 times ULN and excluded patients with Grade 2 or higher peripheral neuropathy.

A total of 449 patients were treated (223 with ADCETRIS + CHP, 226 with CHOP), with 6 cycles planned in 81%. In the ADCETRIS + CHP arm, 70% of patients received 6 cycles, and 18% received 8 cycles. Primary prophylaxis with G-CSF was administered to 34% of ADCETRIS + CHP-treated patients and 27% of CHOP-treated patients.

Fatal adverse reactions occurred in 3% of patients in the A+CHP arm and in 4% of patients in the CHOP arms, most often from infection. Serious adverse reactions were reported in 38% of ADCETRIS + CHP-treated patients and 35% of CHOP-treated patients. Serious adverse reactions occurring in >2% of ADCETRIS + CHP-treated patients included febrile neutropenia (14%), pneumonia (5%), pyrexia (4%), and sepsis (3%).

The most common adverse reactions observed ≥2% more in recipients of ADCETRIS + CHP were nausea, diarrhea, fatigue or asthenia, mucositis, pyrexia, vomiting, and anemia. Other common (≥10%) adverse reactions observed ≥2% more with ADCETRIS + CHP were febrile neutropenia, abdominal pain, decreased appetite, dyspnea, edema, cough, dizziness, hypokalemia, decreased weight, and myalgia.

In recipients of ADCETRIS + CHP, adverse reactions led to dose delays of ADCETRIS in 25% of patients, dose reduction in 9% (most often for peripheral neuropathy), and discontinuation of ADCETRIS with or without the other components in 7% (most often from peripheral neuropathy and infection).

Table 7: Adverse Reactions Reported in ≥10% of ADCETRIS + CHP-treated Patients with Previously Untreated, CD30-Expressing PTCL (Study 6: ECHELON-2)

Body System
Adverse Reaction		 ADCETRIS + CHP Total
N = 223 % of patients		 CHOP Total
N = 226 % of patients
Any Grade Grade 3 Grade 4 Any Grade Grade 3 Grade 4
Blood and lymphatic system disorders
Anemia* 66 13 <1 59 12 <1
Neutropenia* 59 17 22 58 14 22
Lymphopenia* 51 18 1 57 19 2
Febrile neutropenia 19 17 2 16 12 4
Thrombocytopenia* 17 3 3 13 3 2
Gastrointestinal disorders
Nausea 46 2 - 39 2 -
Diarrhea 38 6 - 20 <1 -
Mucositis 30 2 <1 27 3 -
Constipation 29 <1 <1 30 1 -
Vomiting 26 <1 - 17 2 -
Abdominal pain 17 1 - 13 <1 -
Nervous system disorders
Peripheral neuropathy 52 3 <1 55 4 -
Headache 15 <1 - 15 <1 -
Dizziness 13 - - 9 <1 -
General disorders and administration site conditions
Fatigue or asthenia 35 2 - 29 2 -
Pyrexia 26 1 <1 19 - -
Edema 15 <1 - 12 <1 -
Infections and infestations
Upper respiratory tract infection 14 <1 - 15 <1 -
Skin and subcutaneous disorders
Alopecia 26 - - 25 1 -
Rash 16 1 <1 14 1 -
Musculoskeletal and connective tissue disorders
Myalgia 11 - - 8 - -
Respiratory, thoracic and mediastinal disorders
Dyspnea 15 2 - 11 2 -
Cough 13 <1 - 10 - -
Metabolism and nutrition disorders
Decreased appetite 17 1 - 12 1 -
Hypokalemia 12 4 - 8 <1 <1
Investigations
Weight decreased 12 <1 - 8 <1 -
Psychiatric disorders
Insomnia 11 - - 14 - -
* Derived from laboratory values and adverse reaction data. Laboratory values were obtained at the start of each cycle and end of treatment.
The table includes a combination of grouped and ungrouped terms. CHP = cyclophosphamide, doxorubicin, and prednisone; CHOP = cyclophosphamide, doxorubicin, vincristine, and prednisone
Events were graded using the NCI CTCAE Version 4.03

Relapsed Systemic Anaplastic Large Cell Lymphoma (Study 2)

ADCETRIS was studied in 58 patients with sALCL in a single arm clinical trial in which the recommended starting dose and schedule was 1.8 mg/kg intravenously every 3 weeks. Median duration of treatment was 7 cycles (range, 1-16) [see Clinical Studies].

Adverse reactions that led to dose delays in more than 5% of ADCETRIS-treated patients were neutropenia (12%) and peripheral sensory neuropathy (7%) [see DOSAGE AND ADMINISTRATION]. Adverse reactions led to treatment discontinuation in 19% of ADCETRIS-treated patients. The adverse reaction that led to treatment discontinuation in 2 or more patients was peripheral sensory neuropathy (5%). Serious adverse reactions were reported in 41% of ADCETRIS-treated patients. The most common serious adverse reactions were septic shock (3%), supraventricular arrhythmia (3%), pain in extremity (3%), and urinary tract infection (3%).

Table 8: Adverse Reactions Reported in ≥10% of Patients with Relapsed Systemic Anaplastic Large Cell Lymphoma (Study 2)

Body System
Adverse Reaction		 sALCL Total
N = 58 % of patients
Any Grade Grade 3 Grade 4
Blood and lymphatic system disorders
Neutropenia* 55 12 9
Anemia* 52 2 -
Thrombocytopenia* 16 5 5
Lymphadenopathy 10 - -
Nervous system disorders
Peripheral sensory neuropathy 53 10 -
Headache 16 2 -
Dizziness 16 - -
General disorders and administration site conditions
Fatigue 41 2 2
Pyrexia 38 2 -
Chills 12 - -
Pain 28 - 5
Edema peripheral 16 - -
Infections and infestations
Upper respiratory tract infection 12 - -
Gastrointestinal disorders
Nausea 38 2 -
Diarrhea 29 3 -
Vomiting 17 3 -
Constipation 19 2 -
Skin and subcutaneous tissue disorders
Rash 31 - -
Pruritus 19 - -
Alopecia 14 - -
Dry skin 10 - -
Respiratory, thoracic and mediastinal disorders
Cough 17 - -
Dyspnea 19 2 -
Musculoskeletal and connective tissue disorders
Myalgia 16 2 -
Back pain 10 2 -
Pain in extremity 10 2 2
Muscle spasms 10 2 -
Psychiatric disorders
Insomnia 16 - -
Metabolism and nutrition disorders
Decreased appetite 16 2 -
Investigations
Weight decreased 12 3 -
*Derived from laboratory values and adverse reaction data
Events were graded using the NCI CTCAE Version 3.0

Primary Cutaneous Anaplastic Large Cell Lymphoma And CD30-Expressing Mycosis Fungoides (Study 4: ALCANZA)

ADCETRIS was studied in 131 patients with pcALCL or CD30-expressing MF requiring systemic therapy in a randomized, open-label, multicenter clinical trial in which the recommended starting dose and schedule was ADCETRIS 1.8 mg/kg intravenously over 30 minutes every 3 weeks or physician's choice of either methotrexate 5 to 50 mg orally weekly or bexarotene 300 mg/m² orally daily.

Of the 131 enrolled patients, 128 (66 brentuximab vedotin, 62 physician's choice) received at least one dose of study treatment. The median number of treatment cycles in the ADCETRIS treatment arm was 12 (range, 1-16) compared to 3 (range, 1-16) and 6 (range, 1-16) in the methotrexate and bexarotene arms, respectively. Twenty-four (24) patients (36%) in the ADCETRIS-treatment arm received 16 cycles compared to 5 patients (8%) in the physician's choice arm [see Clinical Studies].

Adverse reactions that led to dose delays in more than 5% of ADCETRIS-treated patients were peripheral sensory neuropathy (15%) and neutropenia (6%) [see DOSAGE AND ADMINISTRATION]. Adverse reactions led to treatment discontinuation in 24% of ADCETRIS-treated patients. The most common adverse reaction that led to treatment discontinuation was peripheral neuropathy (12%). Serious adverse reactions were reported in 29% of ADCETRIS-treated patients. The most common serious adverse reactions were cellulitis (3%) and pyrexia (3%).

Table 9: Adverse Reactions Reported in ≥10% ADCETRIS-Treated Patients with pcALCL or CD30-Expressing MF (Study 4: ALCANZA)

Body System
Adverse Reaction		 ADCETRIS Total
N = 66 % of patients		 Physician’s Choicea Total
N = 62 % of patients
Any Grade Grade 3 Grade 4 Any Grade Grade 3 Grade 4
Blood and lymphatic system disorders
Anemia* 62 - - 65 5 -
Neutropenia* 21 3 2 24 5 -
Thrombocytopenia* 15 2 2 2 - -
Nervous system disorders
Peripheral sensory neuropathy 45 5 - 2 - -
Gastrointestinal disorders
Nausea 36 2 - 13 - -
Diarrhea 29 3 - 6 - -
Vomiting 17 2 - 5 - -
General disorders and administration site conditions
Fatigue 29 5 - 27 2 -
Pyrexia 17 - - 18 2 -
Edema peripheral 11 - - 10 - -
Asthenia 11 2 - 8 - 2
Skin and subcutaneous tissue disorders
Pruritus 17 2 - 13 3 -
Alopecia 15 - - 3 - -
Rash maculo-papular 11 2 - 5 - -
Pruritus generalized 11 2 - 2 - -
Metabolism and nutrition disorders
Decreased appetite 15 - - 5 - -
Musculoskeletal and connective tissue disorders
Arthralgia 12 - - 6 - -
Myalgia 12 - - 3 - -
Respiratory, thoracic and mediastinal disorders
Dyspnea 11 - - - - -
*Derived from laboratory values and adverse reaction data
a Physician's choice of either methotrexate or bexarotene
Events were graded using the NCI CTCAE Version 4.03

Additional Important Adverse Reactions

Infusion reactions

In studies of ADCETRIS as monotherapy (Studies 1-4), 13% of ADCETRIS-treated patients experienced infusion-related reactions. The most common adverse reactions in Studies 1-4 (≥3% in any study) associated with infusion-related reactions were chills (4%), nausea (3-4%), dyspnea (2-3%), pruritus (2-5%), pyrexia (2%), and cough (2%). Grade 3 events were reported in 5 of the 51 ADCETRIS-treated patients who experienced infusion-related reactions.

In a study of ADCETRIS in combination with AVD (Study 5, ECHELON-1), infusion-related reactions were reported in 57 patients (9%) in the ADCETRIS + AVD-treated arm. Grade 3 events were reported in 3 of the 57 patients treated with ADCETRIS + AVD who experienced infusion-related reactions. The most common adverse reaction (≥2%) associated with infusion-related reactions was nausea (2%).

In a study of ADCETRIS in combination with CHP (Study 6, ECHELON-2), infusion-related reactions were reported in 10 patients (4%) in the ADCETRIS + CHP-treated arm: 2 (1%) patients with events that were Grade 3 or higher events, and 8 (4%) patients with events that were less than Grade 3.

Pulmonary Toxicity

In a trial in patients with cHL that studied ADCETRIS with bleomycin as part of a combination regimen, the rate of non-infectious pulmonary toxicity was higher than the historical incidence reported with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). Patients typically reported cough and dyspnea. Interstitial infiltration and/or inflammation were observed on radiographs and computed tomographic imaging of the chest. Most patients responded to corticosteroids. The concomitant use of ADCETRIS with bleomycin is contraindicated [see CONTRAINDICATIONS].

In a study of ADCETRIS in combination with AVD (Study 5, ECHELON-1), non-infectious pulmonary toxicity events were reported in 12 patients (2%) in the ADCETRIS + AVD arm. These events included lung infiltration (6 patients) and pneumonitis (6 patients), or interstitial lung disease (1 patient).

In a study of ADCETRIS in combination with CHP (Study 6, ECHELON-2), non-infectious pulmonary toxicity events were reported in 5 patients (2%) in the ADCETRIS + CHP arm; all 5 events were pneumonitis.

Cases of pulmonary toxicity have also been reported in patients receiving ADCETRIS monotherapy. In Study 3 (AETHERA), pulmonary toxicity was reported in 8 patients (5%) in the ADCETRIS-treated arm and 5 patients (3%) in the placebo arm.

Post Marketing Experience

The following adverse reactions have been identified during post-approval use of ADCETRIS. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and lymphatic system disorders: febrile neutropenia [see WARNINGS AND PRECAUTIONS].

Gastrointestinal disorders: acute pancreatitis and gastrointestinal complications (including fatal outcomes) [see WARNINGS AND PRECAUTIONS].

Hepatobiliary disorders: hepatotoxicity [see WARNINGS AND PRECAUTIONS].

Infections: PML [see BOXED WARNING, WARNINGS AND PRECAUTIONS], serious infections and opportunistic infections [see WARNINGS AND PRECAUTIONS].

Metabolism and nutrition disorders: hyperglycemia [see WARNINGS AND PRECAUTIONS].

Respiratory, thoracic and mediastinal disorders: noninfectious pulmonary toxicity including pneumonitis, interstitial lung disease, and ARDS (some with fatal outcomes) [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].

Skin and subcutaneous tissue disorders: Toxic epidermal necrolysis, including fatal outcomes [see WARNINGS AND PRECAUTIONS].

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to ADCETRIS in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

Patients with cHL and sALCL in Studies 1 and 2 [see Clinical Studies] were tested for antibodies to brentuximab vedotin every 3 weeks using a sensitive electrochemiluminescence immunoassay. Approximately 7% of patients in these trials developed persistently positive antibodies (positive test at more than 2 time points) and 30% developed transiently positive antibodies (positive at 1 or 2 post-baseline time points). The antibrentuximab antibodies were directed against the antibody component of brentuximab vedotin in all patients with transiently or persistently positive antibodies. Two of the patients (1%) with persistently positive antibodies experienced adverse reactions consistent with infusion reactions that led to discontinuation of treatment. Overall, a higher incidence of infusion related reactions was observed in patients who developed persistently positive antibodies.

A total of 58 patient samples that were either transiently or persistently positive for antibrentuximab vedotin antibodies were tested for the presence of neutralizing antibodies. Sixty-two percent (62%) of these patients had at least one sample that was positive for the presence of neutralizing antibodies. The effect of anti-brentuximab vedotin antibodies on safety and efficacy is not known.

Read the entire FDA prescribing information for Adcetris (Brentuximab Vedotin)

&Copy; Adcetris Patient Information is supplied by Cerner Multum, Inc. and Adcetris Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.