ADCETRIS

What it is

ADCETRIS contains 50 mg brentuximab vedotin per vial. It is a powder for injection presented as a white to off-white lyophilised cake or powder. Following reconstitution with 10.5 mL sterile water for injection, a solution containing 5 mg/mL brentuximab vedotin is produced.

Approved indications

— Treatment of patients with previously untreated CD30+ Stage III or Stage IV Hodgkin lymphoma in combination with doxorubicin, vinblastine, and dacarbazine (AVD). — Treatment of adult patients with previously untreated CD30+ Stage IIB with large mediastinal mass and/or extranodal disease, Stage III or Stage IV Hodgkin lymphoma in combination with etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone (BrECADD). — Treatment of adult patients with CD30+ Hodgkin lymphoma at higher risk of relapse or progression following ASCT. — Treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma: following autologous stem cell transplant (ASCT) or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option. — Treatment of adult patients with previously untreated CD30+ peripheral T-cell lymphoma in combination with cyclophosphamide, doxorubicin, and prednisone (CHP). — Treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). — Treatment of adult patients with CD30+ cutaneous T-cell lymphoma after at least 1 prior systemic therapy.

Dosing overview

For previously untreated Hodgkin lymphoma in combination with doxorubicin, vinblastine and dacarbazine (AVD), the recommended dose is 1.2 mg/kg administered as an intravenous infusion over 30 minutes on days 1 and 15 of each 28-day cycle for 6 cycles. For previously untreated Hodgkin lymphoma in combination with etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone (BrECADD), the recommended dose is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks for up to 6 cycles. For relapsed or refractory Hodgkin lymphoma, the recommended dose is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks. For Hodgkin lymphoma at risk of relapse or progression following ASCT, the recommended dose is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks. For previously untreated peripheral T-cell lymphoma in combination with cyclophosphamide, doxorubicin, and prednisone (CHP), the recommended dose is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks for 6 to 8 cycles. For relapsed or refractory systemic anaplastic large cell lymphoma, the recommended dose is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks. For relapsed or refractory cutaneous T-cell lymphoma after prior systemic treatment, the recommended dose is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks. If the patient's weight is more than 100 kg, the dose calculation should use 100 kg. The maximal recommended dose is 180 mg.

Key safety warnings

John Cunningham virus (JCV) reactivation resulting in progressive multifocal leukoencephalopathy (PML) and death can occur in ADCETRIS-treated patients. PML has been reported in patients who received this treatment after receiving multiple prior chemotherapy regimens. PML is a rare demyelinating disease of the central nervous system that results from reactivation of latent JCV and is often fatal. Patients should be closely monitored for new or worsening neurological, cognitive, or behavioural signs or symptoms, which may be suggestive of PML. ADCETRIS dosing should be held for any suspected case of PML. Cases of pulmonary toxicity including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome (ARDS), some with fatal outcomes, have been reported in patients receiving ADCETRIS. Although a causal association with ADCETRIS has not been established, the risk of pulmonary toxicity cannot be ruled out. Cases of pulmonary toxicity most commonly developed during the first 5 cycles of ADCETRIS and presented with cough, dyspnoea and interstitial lung infiltrates on radiological studies. Acute pancreatitis has been observed in patients treated with ADCETRIS. Fatal outcomes have been reported. Patients should be closely monitored for new or worsening abdominal pain, which may be suggestive of acute pancreatitis. Serious infections such as pneumonia, staphylococcal bacteraemia, sepsis/septic shock (including fatal outcomes) and herpes zoster, cytomegalovirus (CMV) (reactivation) and opportunistic infections such as Pneumocystis jiroveci pneumonia and oral candidiasis have been reported in patients treated with ADCETRIS. Patients should be carefully monitored during treatment for the emergence of possible serious and opportunistic infections. ADCETRIS treatment may cause a peripheral neuropathy, both sensory and motor. ADCETRIS-induced peripheral neuropathy is typically an effect of cumulative exposure to this medicinal product and is reversible in most cases with a 16-week median time from onset to resolution. Grade 3 or Grade 4 anaemia, thrombocytopenia, and prolonged (≥1 week) Grade 3 or Grade 4 neutropenia can occur with ADCETRIS. Complete blood counts should be monitored prior to administration of each dose. Cases of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with ADCETRIS. Fatal outcomes have been reported for SJS and TEN. Serious gastrointestinal (GI) complications including intestinal obstruction, ileus, enterocolitis, neutropenic colitis, erosion, ulcer, perforation and haemorrhage, some with fatal outcomes, have been reported in patients treated with ADCETRIS. Some cases of GI perforations were reported in lymphoma patients with pre-existing GI involvement. Cases of hepatotoxicity, ranging from asymptomatic elevations in serum transaminase levels to hepatic failure and fulminant hepatitis have been reported in patients receiving ADCETRIS. These have included fatal outcomes. Pre-existing liver disease, comorbidities, and concomitant medications may increase the risk of serious or fatal hepatotoxicity.

Contraindications

Hypersensitivity to the active substance or to any of the excipients is a contraindication. Combined use of bleomycin and ADCETRIS causes pulmonary toxicity.

PBS listing

The 50 mg powder for intravenous infusion strength has 22 PBS items listed with authority required restriction at an ex-manufacturer price of A$4422.25.

Regulatory history

ADCETRIS was first listed on the ARTG on 2013-12-20 as a registered medicine (licence category RE) containing brentuximab vedotin 50 mg powder for injection vial, sponsored by Takeda Pharmaceuticals. The initial approval on 2013-12-19 covered treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma following autologous stem cell transplant (ASCT) or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). In November 2014, the PBAC recommended against listing for relapsed or refractory CD30 positive Hodgkin lymphoma, considering the clinical evidence not robust enough to support superior efficacy over best supportive care and the proposed price unacceptably high. In November 2016, the PBAC recommended listing for relapsed Hodgkin lymphoma in ASCT naïve patients and for relapsed or refractory Hodgkin lymphoma following autologous stem cell transplant failure. In December 2017, the PBAC recommended removal of the requirement for an additional biopsy from the initial treatment restriction for CD30+ systemic anaplastic large cell lymphoma, considering CD30+ status typically constant. In November 2018, listing was recommended for refractory or relapsed CD30 positive cutaneous T-cell lymphomas (CTCL) (excluding lymphomatoid papulosis CTCL subtype) as a Section 100 authority required listing. In March 2021, the PBAC recommended listing for first-line treatment of CD30 positive peripheral T-cell lymphoma in combination with CHP. In July 2025, the PBAC recommended listing for first-line treatment of advanced Hodgkin lymphoma in combination with doxorubicin, vinblastine and dac