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  See full Prescribing Information, including BOXED WARNING  nav_triangle See Important Safety Information  nav_triangle  
ADCETRIS® (brentuximab vedotin) is indicated for the treatment of adult patients with previously untreated Stage III/IV classical Hodgkin lymphoma (cHL) in combination with chemotherapy.
See A+AVD vs ABVD clinical data nav_triangle
 
 
Keep patients on schedule
with ADCETRIS + AVD
 
reco_dosage  
 
 
*The dose for patients weighing >100 kg should be calculated based on a weight of 100 kg.
 
BOXED WARNING
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.
 
The safety profile of ADCETRIS is well established. Neutropenia and peripheral neuropathy associated with ADCETRIS + AVD (A+AVD) are predictable and manageable. Key treatment recommendations help you keep your patients on schedule and manage these reactions.1
 
A+AVD = ADCETRIS + doxorubicin, vinblastine, dacarbazine; ABVD = doxorubicin, bleomycin, vinblastine, dacarbazine.
 
blue_triangle SEE ADDITIONAL IMPORTANT SAFETY INFORMATION BELOW. blue_triangle
 
 
RECOMMENDATION 1: G-CSF primary prophylaxis for
A+AVD patients, starting with Cycle 11
 
 
G-CSF primary prophylaxis decreased the incidence of neutropenia and febrile neutropenia1
 
 
ASCO guidelines recommend use of G-CSF primary prophylaxis with febrile neutropenia risk ≥20%2
 
Monitor complete blood counts (CBC) prior to each dose. Monitor more frequently for patients with Grade 3 or 4 neutropenia. Monitor patients for fever1
 
In the frontline clinical trial, neutropenia led to dose delays of ≥1 drug in 21% of patients; febrile neutropenia led to dose delays in 8% of patients1
 
Dose modifications for Grade 3 or 4 neutropenia: Administer G-CSF prophylaxis for subsequent cycles for patients not receiving primary G-CSF prophylaxis.1
 
 
 
 
 
RECOMMENDATION 2: Early detection and management of peripheral neuropathy (PN)
 
 
PN with A+AVD
 
PN resolved or improved by ≥1 grade at last follow-up in the majority of patients1
 
 
†At the time of last follow-up.
 
Monitoring and managing PN
 
ADCETRIS treatment causes PN that is predominantly sensory; cases of peripheral motor neuropathy have also been reported (65% sensory and 11% motor in the frontline clinical trial). ADCETRIS-induced PN is cumulative1
 
In the frontline clinical trial, median time to onset of any grade PN was 8 weeks (range, 0-29); median time from onset to resolution or improvement (≥1 grade) of any grade was 10 weeks (range, 0-139)1
 
Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness1
 
Counsel patients to report any numbness or tingling in hand or feet, or muscle weakness1
 
In the frontline clinical trial, 7% of A+AVD patients discontinued one or more drugs due
to PN1
 
Dose Modifications for PN1:
 
Grade 2: Reduce dose to 0.9 mg/kg up to a maximum of 90 mg* every 2 weeks
 
Grade 3: Hold 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
 
Grade 4: Discontinue dosing
 
*The dose for patients weighing >100 kg should be calculated based on a weight of 100 kg.
 
 
 
 
ECHELON-1 Clinical Trial Design
 
A randomized, open-label, multicenter trial assessing the efficacy and safety of A+AVD vs ABVD in 1334 adult patients with newly diagnosed Stage III/IV cHL. 664 patients were randomized to receive 1.2 mg/kg of ADCETRIS administered as an IV infusion over 30 minutes every 2 weeks for up to 12 doses + AVD, and 670 patients were randomized to 12 doses of ABVD. The primary endpoint was modified progression-free survival per independent review facility. The key secondary endpoint was overall survival.1,3
 
cta_2
 
 
 
Important Safety Information
 
BOXED WARNING
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.
 
Contraindication
ADCETRIS concomitant with 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. Institute dose modifications accordingly.
   
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 starting with Cycle 1 for previously untreated patients who receive ADCETRIS in combination with chemotherapy for Stage III/IV 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 bacterial, fungal, or viral infections.
   
Tumor lysis syndrome: Closely monitor patients with rapidly proliferating tumor and high tumor burden.
   
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. 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 compared to patients with normal hepatic
function. 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.
   
Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus, and to avoid pregnancy during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.
   
Most Common (≥20%) Adverse Reactions in All Clinical Trials
Neutropenia, anemia, peripheral sensory neuropathy, nausea, fatigue, constipation, diarrhea, vomiting, and pyrexia.
 
Most Common (≥20%) Adverse Reactions in ECHELON-1 Patients
Treated With A+AVD
Anemia, neutropenia, peripheral sensory neuropathy, constipation, vomiting, diarrhea, pyrexia, decreased weight, stomatitis, abdominal pain.
 
Drug Interactions
Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors, has the potential to affect the exposure to monomethyl auristatin E (MMAE).
 
Use in Specific Populations
Moderate or severe hepatic impairment or severe renal impairment: MMAE exposure and adverse reactions are increased. Avoid use.
 
Advise males with female sexual partners of reproductive potential to use effective contraception during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.
 
Advise patients to report pregnancy immediately and avoid breastfeeding while receiving ADCETRIS.
 
Please see full Prescribing Information, including BOXED WARNING, here
 
References: 1. ADCETRIS [Prescribing Information], Bothell, WA: Seattle Genetics, Inc. March 2018.
2. Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the use of WBC growth factors: American Society of Clinical Oncology Clinical Practice Guideline update. J Clin Oncol. 2015;33:3199-3212.
3. Connors JM, Jurczak W, Straus DJ, et al. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin’s lymphoma. N Engl J Med. 2018;378:331-344.
 
 
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ADCETRIS and its logo, and Seattle Genetics and , are US registered trademarks of Seattle Genetics, Inc.
© 2018 Seattle Genetics, Inc., Bothell, WA 98021
All rights reserved     USP-BVP-2017-0222(1)
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