Previously Untreated Advanced-Stage cHL: What are the Long-Term PFS Data for a Treatment Option?

By Seagen FEATURING Adam Forman
January 12, 2022

Indications and Important Safety Information 



ADCETRIS® (brentuximab vedotin) for injection is indicated for the treatment of adult patients with previously untreated Stage III/IV classical Hodgkin lymphoma (cHL)  in combination with doxorubicin, vinblastine, and dacarbazine.



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



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 beginning with Cycle 1 for patients who receive  ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL. 

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 ifPML 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 pre-existing 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 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% in any study) Adverse Reactions 

Peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection,  pyrexia, constipation, vomiting, alopecia, decreased weight, abdominal pain, anemia,  stomatitis, lymphopenia, and mucositis. 

Drug Interactions 

Concomitant use of strong CYP3A4 inhibitors or inducers 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

Comments are disabled for this content.