Brentuximab vedotin

ADCETRIS is a CD30-directed antibody and microtubule inhibitor conjugate indicated for treatment of: • Adult patients with previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine. • Pediatric patients 2 years and older with previously untreated high risk classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide. • Adult patients with classical Hodgkin lymphoma (cHL) at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation. • Adult patients with classical Hodgkin lymphoma (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.

CD30 is a member of the tumor necrosis factor receptor family and is expressed on the surface of sALCL cells and on Hodgkin Reed-Sternberg (HRS) cells in cHL. CD30 is variably expressed in other T-cell lymphomas. Expression of CD30 on healthy tissue and cells is limited. In vitro data suggest that signaling through CD30-CD30L binding may affect cell survival and proliferation. Brentuximab vedotin is an antibody-drug conjugate (ADC). The antibody is a chimeric IgG1 directed against CD30. The small molecule, MMAE, is a microtubule-disrupting agent. MMAE is covalently attached to the antibody via a linker. Nonclinical data suggest that the anticancer activity of ADCETRIS is due to the binding of the ADC to CD30-expressing cells, followed by internalization of the ADC‑CD30 complex, and the release of MMAE via proteolytic cleavage.

• Administer only as an intravenous infusion over 30 minutes. • 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. • 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.

ADCETRIS is contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation). Concomitant use with bleomycin due to pulmonary toxicity.

Boxed warning (progressive multifocal leukoencephalopathy (pml) jc): virus infection resulting in PML and death can occur in patients receiving ADCETRIS. WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS. • Peripheral neuropathy: Monitor patients for neuropathy and institute dose modifications accordingly. • Anaphylaxis and infusion reactions: If an infusion reaction occurs, interrupt the infusion. If anaphylaxis occurs, immediately discontinue the infusion. • Hematologic toxicities: Monitor complete blood counts. Monitor for signs of infection. Manage using dose delays and growth factor support. • Serious infections and opportunistic infections: Closely monitor patients for the emergence of bacterial, fungal or viral infections.

The following clinically significant adverse reactions are described elsewhere in the labeling: • Peripheral Neuropathy • Anaphylaxis and Infusion Reactions • Hematologic Toxicities • Serious Infections and Opportunistic Infections • Tumor Lysis Syndrome o Increased Toxicity in the Presence of Severe Renal Impairment • Increased Toxicity in the Presence of Moderate or Severe Hepatic Impairment • Hepatotoxicity • Progressive Multifocal Leukoencephalopathy • Pulmonary Toxicity • Serious Dermatologic Reactions • Gastrointestinal Complications • Hyperglycemia The most common adverse reactions (≥20%) are peripheral neuropathy, nausea, fatigue, musculoskeletal pain, constipation, diarrhea, vomiting, pyrexia, upper respiratory tract infection, mucositis, abdominal pain, and rash.

Concomitant use of strong CYP3A4 inhibitors or inducers has the potential to affect the exposure to monomethyl auristatin E (MMAE). Effect of Other Drugs on ADCETRIS CYP3A4 Inhibitors: Co-administration of ADCETRIS with ketoconazole, a potent CYP3A4 inhibitor, increased exposure to MMAE, which may increase the risk of adverse reaction. Closely monitor adverse reactions when ADCETRIS is given concomitantly with strong CYP3A4 inhibitors.

Storage Store vial refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light.