Indications and Usage

• Primary Treatment: Adcetris is approved for use in adult patients with previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with chemotherapy regimens like doxorubicin, vinblastine, and dacarbazine (AVD).

• Pediatric Use: It is also indicated for pediatric patients aged 2 years and older with previously untreated high-risk cHL, in combination with a regimen including doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide.

• Relapsed or Refractory Settings: Adcetris is used in adults with cHL after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates. It is also indicated for systemic anaplastic large cell lymphoma (sALCL) and other CD30-expressing peripheral T-cell lymphomas (PTCL) after failure of other chemotherapies.

Administration and Dosing

• Typical dosing for Adcetris involves 1.8 mg/kg given intravenously over 30 minutes every 3 weeks. A maximum of 180 mg per dose should not be exceeded.

• For HL and ALCL without stem cell transplant, Adcetris can be administered until disease progression or unacceptable toxicity.

• Dose Adjustments: Dosing adjustments may be necessary for patients with hepatic impairment or severe renal impairment. It is contraindicated in patients with severe renal impairment (CrCL <30 mL/min).

Mechanism of Action

• Brentuximab vedotin combines an anti-CD30 monoclonal antibody with the cytotoxic agent monomethyl auristatin E. Following binding to CD30-expressing cells, the conjugate is internalized, releasing the cytotoxic agent within the cell and inducing cell death.

Boxed Warnings and Precautions

• Progressive Multifocal Leukoencephalopathy (PML): Adcetris carries a boxed warning for PML, a rare but serious brain infection that can result in death. Monitoring for new or worsening neurological symptoms is essential.

• Pulmonary Toxicity: Co-administration with bleomycin is contraindicated due to an increased risk of pulmonary toxicity.

Common Adverse Reactions

• Peripheral Neuropathy: This is one of the most common adverse effects, potentially requiring dose modification or discontinuation.

• Infusion Reactions: Infusion reactions can occur; pre-medicating with antipyretics and antihistamines is advisable.

• Hematological Toxicities: Neutropenia, anemia, and thrombocytopenia are common, necessitating regular monitoring of complete blood counts.

• Other common adverse effects include fatigue, nausea, fever, rash, and diarrhea.

Drug Interactions

• CYP3A4 Inhibitors and Inducers: Adcetris metabolism may be affected by drugs that inhibit or induce CYP3A4, potentially requiring dose adjustment and careful monitoring.

Use in Specific Populations

• Pregnancy and Lactation: Adcetris should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Women of childbearing potential should use effective contraception during treatment and for 6 months after the last dose. Breastfeeding is not recommended during treatment with Adcetris.

• Dose adjustments may be necessary for patients with severe renal impairment (CrCl <30 mL/min) or moderate to severe hepatic impairment.

Monitoring and Follow-Up

• Complete blood counts (CBC) should be monitored prior to each dose; dose adjustments may be needed in case of severe hematologic toxicities.

• Monitor liver function tests periodically due to the risk of hepatotoxicity.

• Regularly assess patients for signs of infection, as neutropenia can increase infection risk.

Patient Counseling Points:

• Educate patients about the risk of potential side effects, particularly neuropathy and infusion reactions.

• Instruct patients to report any new symptoms, especially those involving changes in neurological status or symptoms suggestive of infection.

• Advise women of reproductive potential to use effective contraception during treatment and for a minimum period post-treatment (as specified by product labeling).

Handling and Administration:

• Adcetris is a cytotoxic drug and should be handled with caution. Appropriate protective measures including the use of gloves and other personal protective equipment should be utilized during preparation and administration.

• Unused portions of the drug or waste materials should be disposed of in accordance with local regulations for hazardous waste.