Adults with

Previously untreated
Stage III/IV cHL

Safety

Amina, a patient treated with ADCETRIS® (brentuximab vedotin)+AVD.

Amina, treated with ADCETRIS+AVD.

Most Common Adverse Events

ADCETRIS+AVD has a well-established safety profile

Adverse reactions reported in ≥10% of ECHELON-1 patients treated with A+AVD at primary analysis1

 
A+AVD (total n = 662), % of patients
ABVD (total n = 659), % of patients
Adverse reaction
Any Grade
Grade 3
Grade 4
Any Grade
Grade 3
Grade 4
Adverse reaction
Grade
Grade
Any34Any34
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 exanthems
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 reference irrespective of rate between arms.
Grouped term includes rash maculopapular, rash macular, rash, rash papular, rash generalized, and rash vesicular.
 
Events were graded using the NCI CTCAE Version 4.03.
 
Events listed are those having a ≥5% difference in rate between treatment arms.
 
ABVD = doxorubicin, bleomycin, vinblastine, dacarbazine; A+AVD = ADCETRIS + doxorubicin, vinblastine, dacarbazine; CTCAE = common terminology criteria for adverse events; NCI = National Cancer Institute.

SARs, Discontinuations, Deaths

Serious adverse reactions, dose discontinuations, and on-study deaths

Febrile neutropenia and pyrexia were the most common

serious adverse reactions in both arms1,8

Serious adverse reactions
A+AVD (n = 662)
ABVD (n = 659)
Overall rate
43%
27%
Most common
Febrile neutropenia (17%),
pyrexia (7%), neutropenia and
pneumonia (3% each)
Febrile neutropenia (7%),
pyrexia (4%)

Neutropenia was the most common reason for dose delay in both arms1,8

Dose delays (<1 drug in 5% of patients)
A+AVD (n = 662)
ABVD (n = 659)
Rate due to adverse reaction
Neutropenia (21%),
febrile neutropenia (8%)
Neutropenia (15%)

Rates of dose discontinuation1,8

Dose discontinuation (≥1 drug)
A+AVD (n = 662)
ABVD (n = 659)
Overall rate
13%
16%
Rate due to PN
7%
2%

On-study deaths§1,8

  1. A+AVD: 9 on-study deaths (7 due to neutropenia; none of these patients had received G-CSF prior to developing neutropenia)
  2. ABVD: 13 on-study deaths (11 due to pulmonary-related toxicity)**
 
§ Deaths that occurred within 30 days of last study dose.8
 
2 deaths were due to myocardial infarction.8
 
** 1 death was due to cardiopulmonary failure. Cause of other death unknown.8
 
G-CSF = granulocyte colony–stimulating factor; SAR = serious adverse reaction.

Peripheral Neuropathy (PN) Resolution Rates

Peripheral neuropathy was identifiable, manageable, and resolved in most cases within 6 years1

The 3-, 4-, and 5-year data provided are not contained in the approved product labeling.
Data are provided as supportive clinical information.

PN incidence and resolution rates within 6 years

PN in patients treated with A+AVD in ECHELON-1 at 2 years1,3

  1. 67% (442/662) experienced PN
    1. Grade 1 or 2: 56% (372/662)
    2. ≥Grade 3: 11% (70/662)
  2.  
  3. Median time to onset (range)
    1. Any grade: 2 months (0-7)
    2. Grade 2: 3 months (0-6)
    3. Grade 3: 4 months (<1-7)
  1. 7% (44/662) discontinued due to PN

PN in patients treated with A+AVD in ECHELON-1 at 6 years1

  1. Median time to partial improvement (range)
    1. 2.9 months (<1-50)
  1. Median time to complete improvement (range)
    1. <6.6 months (<1-67)

PN is recorded as last observation carried forward.

Address PN as early as possible with dose modifications

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Recommended dose: 1.2 mg/kg up to a maximum of 120 mg§ in combination with AVD every 2 weeks until a maximum of 12 doses, disease progression, or unacceptable toxicity1

Severity

Grade 2

Grade 3

Grade 4

Dose modifications for PN

  1. Reduce dose to 0.9 mg/kg up to a maximum of 90 mg§ every 2 weeks
  1. Hold ADCETRIS dosing until improvement to Grade 2 or lower
  2. Restart at 0.9 mg/kg up to a maximum of 90 mg§ every 2 weeks
  3. Consider modifying dose of other neurotoxic chemotherapy agents
  1. Discontinue dosing

Please see all additional dosing modifications

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Patients who develop PN may be able to receive 6 full cycles of treatment with dose modifications1

§

The dose for patients weighing >100 kg should be calculated based on a weight of 100 kg.1

NCI CTCAE Version 4.03 was used in the ECHELON-1 trial, and Version 5.0, current at time of publication (September 2023), is shown here for reference7:

  1. Grade 1 sensory PN: asymptomatic
  2. Grade 1 motor PN: asymptomatic; clinical or diagnostic observations only
  3. Grade 2 sensory and motor PN: moderate symptoms; limiting instrumental ADL
  4. Grade 3 sensory and motor PN: severe symptoms; limiting self-care ADL
  5. Grade 4 sensory and motor PN: life-threatening consequences; urgent intervention indicated

ADL = activities of daily living.

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1

Identify Symptoms

  • Early identification and patient education of PN signs and symptoms is important. PN may be cumulative1
  • Proactively monitor for signs and symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness at every appointment1
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2

Communicate Early

  • Ask patients to inform their healthcare team as soon as they experience symptoms of PN
  • PN was manageable and resolved for the majority of patients who experienced it with A+AVD1
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3

Act With Dose Modifications

  • Through appropriate dose reduction and/or holding, some patients who develop PN may still receive all 6 cycles of ADCETRIS1
  • Grades 2 and 3 PN should be managed with dose modification, and Grade 4 PN should be managed with dose discontinuation1

Early detection and intervention of PN is critical if PN is present

Peer perspective on long-term safety

“Clear communication is key to detecting peripheral neuropathy early.”

Dr. Adam Foreman, hematologist-oncologist

Watch video
 
Dr Adam Forman is presenting this program on behalf of Pfizer and is contracted with Pfizer for this service.

G-CSF Primary Prophylaxis

Starting G-CSF primary prophylaxis beginning with Cycle 1 of A+AVD may reduce risk of neutropenia1,3,8

  1. After 75% of patients had started treatment, G-CSF primary prophylaxis was recommended with A+AVD, as observed rates of neutropenia and febrile neutropenia were higher than anticipated1
Graph: Neutropenia and febrile neutropenia rates in ECHELON-1 (review references 1, 3, and 8)

Start primary prophylaxis with G-CSF beginning with Cycle 1.1

 

G-PP = G-CSF primary prophylaxis.

View monitoring and dose modifications for neutropenia1

Expand component
  1. Fatal and serious cases of febrile neutropenia have been reported with ADCETRIS. Prolonged (>1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS
  2. Monitor complete blood counts prior to each dose of ADCETRIS
  3. Monitor more frequently for patients with Grade 3 or 4 neutropenia
  4. Monitor patients for fever
  5. Neutropenia led to dose delays of ≥1 drug in 21% of patients; febrile neutropenia led to dose delays in 8% of patients

Severity

Grade 3 or 4

Dose modifications

Administer G-CSF prophylaxis for subsequent cycles for patients not receiving G-CSF primary prophylaxis

Please refer to recommended dosing information

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Secondary Malignancies

Secondary malignancies among patients treated with A+AVD vs ABVD

This exploratory 6-year analysis was not specified in the protocol, is descriptive in nature, and offers supportive, but not conclusive, results about secondary malignancies reported in ECHELON-1 participants. This analysis was not powered to determine differences between treatment arms.

Graph: 55 secondary malignancies were documented at 6 years (review reference 2)

There was 1 unknown secondary malignancy in the ABVD arm.2

Additional Data

Pregnancies among patients treated with A+AVD vs ABVD, or their partners§§2

This exploratory 6-year analysis was not specified in the protocol, is descriptive in nature, and offers supportive, but not conclusive, results about pregnancies reported by ECHELON-1 participants or their partners. This analysis was not powered to determine differences between treatment arms. Fertility was not formally assessed.1

143 female patients or partners of male patients reported pregnancies at 6 years
§§

Individual female patients or partners of male patients may have recorded multiple pregnancies and multiple pregnancy outcomes.

Live births among patients treated with A+AVD vs ABVD, or their partners¶¶

This exploratory 6-year analysis was not specified in the protocol, is descriptive in nature, and offers supportive, but not conclusive, results about pregnancies reported by ECHELON-1 participants or their partners. This analysis was not powered to determine differences between treatment arms. Fertility was not formally assessed.1

155 live births reported in female patients or partners of male patients at 6 years

¶¶

Multiple patients or partners of male patients recorded more than 1 live birth.2


  1. Per the ECHELON-1 study protocol, female patients who were both lactating and breastfeeding or who had a positive serum pregnancy test during the screening period or a positive pregnancy test on Day 1 before the first dose of study drug were excluded from the study9
  2. In summary, female patients were advised to avoid pregnancy, and male patients were advised to use effective methods of contraception.9 It is unknown how many study participants intended to or tried to have children. It is also unknown whether all pregnancies/births were reported
  3. ADCETRIS can cause fetal harm based on findings from animal studies and the drug’s mechanism of action1
  4. Verify the pregnancy status of females of reproductive potential prior to initiating ADCETRIS therapy1
  5. Advise females of reproductive potential of this potential risk, and to use effective contraception during ADCETRIS treatment and for 2 months after the last dose of ADCETRIS1
  6. Advise females to immediately report pregnancy1
  7. ADCETRIS may damage spermatozoa and testicular tissue, resulting in possible genetic abnormalities1
  8. Advise male patients with female sexual partners of reproductive potential to use effective contraception during ADCETRIS treatment and for 4 months after the last dose of ADCETRIS1

AYA Subgroup Analysis

PN incidence and resolution over 6 years (AYA population)***10

PN incidence and resolution over 6 years (AYA population) (review *** and reference 10)

***PN is recorded as last observation carried forward.

Additional safety data for AYA patients at 6 years

This exploratory 6-year analysis was not specified in the protocol, is descriptive in nature, and offers supportive, but not conclusive, clinical information only. This analysis was not powered to determine differences between treatment arms.

Graph: Patients with secondary malignancies documented at 6 years (review ††† and references 2 and 10)

Female patients or partners of male patients reported pregnancies at 6 years†††2,10

This exploratory 6-year analysis was not specified in the protocol, is descriptive in nature, and offers supportive, but not conclusive, results about pregnancies reported by ECHELON-1 participants or their partners. This analysis was not powered to determine differences between treatment arms.

Female patients or partners of male patients reported pregnancies at 6 years (review †††, ‡‡‡, and references 2 and 10)

†††

Multiple patients or partners of male patients recorded more than one live birth.2


  1. Fertility was not formally assessed1
  2. Per the ECHELON-1 study protocol, female patients who were both lactating and breastfeeding or who had a positive serum pregnancy test during the screening period or a positive pregnancy test on Day 1 before the first dose of study drug were excluded from the study9
  3. In summary, female patients were advised to avoid pregnancy, and male patients were advised to use effective methods of contraception.9 It is unknown how many study participants intended to or tried to have children. It is also unknown whether all pregnancies/births were reported
  4. ADCETRIS can cause fetal harm based on findings from animal studies and the drug’s mechanism of action1
  5. Verify the pregnancy status of females of reproductive potential prior to initiating ADCETRIS therapy1
  6. Advise females of reproductive potential of this potential risk, and to use effective contraception during ADCETRIS treatment and for 2 months after the last dose of ADCETRIS1
  7. Advise females to immediately report pregnancy1
  8. ADCETRIS may damage spermatozoa and testicular tissue, resulting in possible genetic abnormalities1
  9. Advise male patients with female sexual partners of reproductive potential to use effective contraception during ADCETRIS treatment and for 4 months after the last dose of ADCETRIS1

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Important Safety Information

BOXED WARNING

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.

CONTRAINDICATION

Contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).

WARNINGS AND PRECAUTIONS

Peripheral neuropathy (PN): ADCETRIS causes PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor for symptoms such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Patients experiencing new or worsening PN may require a delay, change in dose, or discontinuation of ADCETRIS.

Anaphylaxis and infusion reactions: Infusion-related reactions (IRR), including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an IRR occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid.

Hematologic toxicities: Fatal and serious cases of febrile neutropenia have been reported with ADCETRIS. Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS.

Administer G-CSF primary prophylaxis beginning with Cycle 1 for adult patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL, and pediatric patients who receive ADCETRIS in combination with chemotherapy for previously untreated high risk cHL.

Monitor complete blood counts prior to each ADCETRIS dose. 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 doses.

Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in ADCETRIS-treated patients. Closely monitor patients during treatment for infections.

Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden may be at increased risk. Monitor closely and take appropriate measures.

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. Avoid use in patients with severe renal impairment.

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 or severe hepatic impairment. Avoid use in patients with moderate or severe hepatic impairment.

Hepatotoxicity: Fatal and serious cases have occurred in ADCETRIS-treated patients. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first ADCETRIS dose or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Monitor liver enzymes and bilirubin. Patients with new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.

PML: Fatal cases of JC virus infection resulting in PML have been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS, 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 PML diagnosis in patients with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.

Pulmonary toxicity: Fatal and serious events of noninfectious pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, have been reported. Monitor patients for signs and symptoms, 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 (GI) complications: Fatal and serious cases of acute pancreatitis have been reported. Other fatal and serious 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.

Hyperglycemia: Serious cases, such as new-onset hyperglycemia, exacerbation of preexisting diabetes mellitus, and ketoacidosis (including fatal outcomes) have been reported with ADCETRIS. Hyperglycemia occurred more frequently in patients with high body mass index or diabetes. Monitor serum glucose and if hyperglycemia develops, administer anti-hyperglycemic medications as clinically indicated.

Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of this potential risk, and to use effective contraception during ADCETRIS treatment and for 2 months after the last dose of ADCETRIS. Advise male patients with female partners of reproductive potential to use effective contraception during ADCETRIS treatment and for 4 months after the last dose of ADCETRIS.

ADVERSE REACTIONS

The most common adverse reactions (≥20% in any study) are peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, pyrexia, constipation, vomiting, alopecia, decreased weight, abdominal pain, anemia, stomatitis, lymphopenia, mucositis, thrombocytopenia, and febrile neutropenia.

DRUG INTERACTIONS

Concomitant use of strong CYP3A4 inhibitors has the potential to affect the exposure to monomethyl auristatin E (MMAE). Closely monitor adverse reactions.

USE IN SPECIAL POPULATIONS

Lactation: Breastfeeding is not recommended during ADCETRIS treatment.

Indications

ADCETRIS® (brentuximab vedotin) is indicated for the treatment of:

Previously untreated Stage III/IV cHL

  1. Adult patients with previously untreated Stage III/IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine.

Previously untreated high risk cHL

  1. Pediatric patients 2 years and older with previously untreated high risk cHL, in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide.

cHL post-auto-HSCT consolidation

  1. Adult patients with cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation.

Relapsed cHL

  1. 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.

Previously untreated sALCL or other CD30-expressing PTCL

  1. Adult patients with 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.

Relapsed sALCL

  1. Adult patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen.

Relapsed pcALCL or CD30-expressing MF

  1. Adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

Please see full Prescribing Information, including BOXED WARNING, for ADCETRIS.

Indications and Important Safety Information

BOXED WARNING

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.

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Indications and Important Safety Information

BOXED WARNING

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.

CONTRAINDICATION

Contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).

WARNINGS AND PRECAUTIONS

Peripheral neuropathy (PN): ADCETRIS causes PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor for symptoms such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Patients experiencing new or worsening PN may require a delay, change in dose, or discontinuation of ADCETRIS.

Anaphylaxis and infusion reactions: Infusion-related reactions (IRR), including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an IRR occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid.

Hematologic toxicities: Fatal and serious cases of febrile neutropenia have been reported with ADCETRIS. Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS.

Administer G-CSF primary prophylaxis beginning with Cycle 1 for adult patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL, and pediatric patients who receive ADCETRIS in combination with chemotherapy for previously untreated high risk cHL.

Monitor complete blood counts prior to each ADCETRIS dose. 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 doses.

Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in ADCETRIS-treated patients. Closely monitor patients during treatment for infections.

Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden may be at increased risk. Monitor closely and take appropriate measures.

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. Avoid use in patients with severe renal impairment.

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 or severe hepatic impairment. Avoid use in patients with moderate or severe hepatic impairment.

Hepatotoxicity: Fatal and serious cases have occurred in ADCETRIS-treated patients. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first ADCETRIS dose or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Monitor liver enzymes and bilirubin. Patients with new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.

PML: Fatal cases of JC virus infection resulting in PML have been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS, 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 PML diagnosis in patients with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.

Pulmonary toxicity: Fatal and serious events of noninfectious pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, have been reported. Monitor patients for signs and symptoms, 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 (GI) complications: Fatal and serious cases of acute pancreatitis have been reported. Other fatal and serious 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.

Hyperglycemia: Serious cases, such as new-onset hyperglycemia, exacerbation of preexisting diabetes mellitus, and ketoacidosis (including fatal outcomes) have been reported with ADCETRIS. Hyperglycemia occurred more frequently in patients with high body mass index or diabetes. Monitor serum glucose and if hyperglycemia develops, administer anti-hyperglycemic medications as clinically indicated.

Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of this potential risk, and to use effective contraception during ADCETRIS treatment and for 2 months after the last dose of ADCETRIS. Advise male patients with female partners of reproductive potential to use effective contraception during ADCETRIS treatment and for 4 months after the last dose of ADCETRIS.

ADVERSE REACTIONS

The most common adverse reactions (≥20% in any study) are peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, pyrexia, constipation, vomiting, alopecia, decreased weight, abdominal pain, anemia, stomatitis, lymphopenia, mucositis, thrombocytopenia, and febrile neutropenia.

DRUG INTERACTIONS

Concomitant use of strong CYP3A4 inhibitors has the potential to affect the exposure to monomethyl auristatin E (MMAE). Closely monitor adverse reactions.

USE IN SPECIAL POPULATIONS

Lactation: Breastfeeding is not recommended during ADCETRIS treatment.

Indications

ADCETRIS® (brentuximab vedotin) is indicated for the treatment of:

Previously untreated Stage III/IV cHL

  1. Adult patients with previously untreated Stage III/IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine.

Previously untreated high risk cHL

  1. Pediatric patients 2 years and older with previously untreated high risk cHL, in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide.

cHL post-auto-HSCT consolidation

  1. Adult patients with cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation.

Relapsed cHL

  1. 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.

Previously untreated sALCL or other CD30-expressing PTCL

  1. Adult patients with 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.

Relapsed sALCL

  1. Adult patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen.

Relapsed pcALCL or CD30-expressing MF

  1. Adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

Please see full Prescribing Information, including BOXED WARNING, for ADCETRIS.

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