Adcetris (brentuximab vedotin) - 2 indications

Scroll down for more information on each indication:

Classical Hodgkin lymphoma and Anaplastic large cell lymphoma; approved in August of 2011

General Information

Adcetris (brentuximab vedotin) is an antibody-drug conjugate comprised of an anti-CD30 antibody joined by an enzyme cleavable linker to a potent, synthetic drug payload, monomethyl auristatin E (MMAE), using Seattle Genetics' proprietary technology. Brentuximab vedotin is designed to be stable in the bloodstream, but to release MMAE upon internalization into CD30-expressing tumor cells, resulting in a targeted cell-killing effect.

Adcetris is specifically approved for the following:

Classical Hodgkin lymphoma (cHL)

• Adult patients with previously untreated Stage III or IV cHL, in combination with doxorubicin, vinblastine, and dacarbazine
• Adult patients with cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation
• 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
• Pediatric patients 2 years and older with previously untreated high risk cHL in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide

Anaplastic large cell lymphoma

• 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
• Adult patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen
• Adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy

Adcetris is supplied as a solution for intravenous infusion administered over 30 minutes. Scroll down for recommended dosing/administration for each indication. 

Mechanism of Action

Adcetris (brentuximab vedotin) is a CD30-directed antibody-drug conjugate (ADC) consisting of three components: 1) the chimeric IgG1 antibody cAC10, specific for human CD30, 2) the microtubule disrupting agent MMAE, and 3) a protease-cleavable linker that covalently attaches MMAE to cAC10.

Side Effects

Adverse events associated with the use of Adcetris may include, but are not limited to, the following:

• neutropenia
• peripheral sensory neuropathy
• fatigue
• nausea
• anemia
• upper respiratory tract infection
• diarrhea
• pyrexia
• rash
• thrombocytopenia
• cough
• vomiting

The Adcetris drug label comes with the following Boxed Warning: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML and death can occur in Adcetris-treated patients.

Indication 1: Classical Hodgkin lymphoma (cHL)

Dosing/Administration

The recommended dosage as monotherapy for adult patients is 1.8 mg/kg up to a maximum of 180 mg every 3 weeks

The recommended dosage in combination with chemotherapy for adult patients with previously untreated Stage III or IV cHL is 1.2 mg/kg up to a maximum of 120 mg every 2 weeks for a maximum of 12 doses

The recommended dosage in combination with chemotherapy for pediatric patients 2 years and older with previously untreated high risk cHL is 1.8 mg/kg up to a maximum of 180 mg every 3 weeks for a maximum of 5 doses

Clinical Trial Results
The FDA approval of Adcetris for Hodgkin lymphoma was based on an open-label, single-arm, multicenter trial.The trial enrolled 102 subjects with HL who relapsed after autologous stem cell transplant. The subjects were treated with 1.8 mg/kg of Adcetris intravenously over 30 minutes every three weeks. Efficacy was based on overall response rate (ORR = complete remission [CR] + partial remission [PR]) and duration of response. The ORR was 73% and the median duration of response was 6.7 months.

Indication 2 - Systemic Anaplastic Large Cell Lymphoma

Dosing/Administration

The recommended dosage as monotherapy for adult patients is 1.8 mg/kg up to a maximum of 180 mg every 3 weeks

The recommended dosage in combination with chemotherapy for adult patients with previously untreated PTCL is 1.8 mg/kg up to a maximum of 180 mg every 3 weeks for 6 to 8 doses

Clinical Trial Results
The FDA approval of Adcetris for systemic anaplastic large cell lymphoma was based on an open-label, single-arm, multicenter trial. The trial enrolled 58 subjects who had relapsed after prior therapy. The subjects received 1.8 mg/kg of Adcetris administered intravenously over 30 minutes every three weeks. Efficacy was based on overall response rate (ORR = complete remission [CR] + partial remission [PR]) and duration of response. The ORR was 86% and the median duration of response was 12.6 months.