Brentuximab vedotin is a targeted cancer therapy classified as an antibody-drug conjugate (ADC). This modern anticancer agent delivers a potent chemotherapy drug directly to cancer cells, aiming to minimize harm to healthy tissues throughout the body.
How Brentuximab Vedotin Targets Cancer
Brentuximab vedotin operates as an antibody-drug conjugate (ADC), a sophisticated cancer therapy designed for precise delivery of a chemotherapy agent directly to malignant cells. The ADC consists of two main components: a monoclonal antibody and a chemotherapy drug called monomethyl auristatin E (MMAE).
The antibody is engineered to specifically recognize and bind to CD30, a protein commonly found on the surface of certain cancer cells. Once the antibody attaches to CD30, the complex is internalized. Inside the cancer cell, MMAE is released from the antibody through proteolytic cleavage. This targeted release ensures the chemotherapy primarily affects cancerous cells, reducing exposure to healthy ones. MMAE then disrupts the microtubule network, necessary for cell division, ultimately leading to cancer cell death.
Cancers Treated by Brentuximab Vedotin
Brentuximab vedotin is approved for treating specific types of lymphomas that express the CD30 protein. Its use often depends on the stage of the disease and prior treatments a patient has received. The U.S. Food and Drug Administration (FDA) initially approved brentuximab vedotin in August 2011 for Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL).
For classical Hodgkin lymphoma (cHL), brentuximab vedotin is used in several settings. It is approved for patients whose disease has relapsed or become refractory after an autologous stem cell transplant (ASCT) or after at least two prior multi-agent chemotherapy regimens for those who are not ASCT candidates. The FDA also approved it in March 2018 for adult patients with previously untreated Stage III or IV cHL, in combination with chemotherapy. Furthermore, in November 2022, its approval expanded to include pediatric patients aged 2 years and older with previously untreated high-risk cHL, also in combination with chemotherapy.
Regarding systemic anaplastic large cell lymphoma (sALCL), brentuximab vedotin is approved for patients whose disease has relapsed or become refractory after at least one prior multi-agent chemotherapy regimen. It is also used as a first-line treatment in combination with chemotherapy for sALCL. Other CD30-positive T-cell lymphomas, such as primary cutaneous anaplastic large cell lymphoma (pcALCL) and certain cases of mycosis fungoides (MF) or Sézary Syndrome that express CD30, are also indications for brentuximab vedotin.
Receiving Brentuximab Vedotin Treatment
Brentuximab vedotin is administered as an intravenous (IV) infusion, delivered directly into a vein. This process typically takes place in an outpatient clinic setting, allowing patients to receive treatment without requiring an overnight hospital stay. The infusion duration is usually about 30 minutes.
A common treatment schedule for brentuximab vedotin involves administration every three weeks. The total number of cycles or the duration of therapy can vary based on the specific condition being treated, the patient’s response to the medication, and the presence of any side effects. Healthcare providers may also administer pre-medications before the infusion to help prevent potential infusion-related reactions.
Managing Side Effects
Patients receiving brentuximab vedotin may experience various side effects. Peripheral neuropathy, characterized by numbness, tingling, or pain in the hands and feet, is a common and noteworthy side effect. This neuropathy can be cumulative, meaning it may worsen over time with continued treatment, and in some cases, it can be persistent. Patients should report any new or worsening neurological symptoms to their healthcare team promptly.
Other common side effects include fatigue, nausea, vomiting, diarrhea, and fever. Neutropenia, a reduction in white blood cell count, is also common and increases the risk of infection. To manage neutropenia, growth factors like G-CSF may be recommended, particularly for patients receiving brentuximab vedotin in combination with chemotherapy for previously untreated Stage III or IV cHL. Infusion-related reactions can occur, sometimes up to two days after the infusion, and can range in severity.
Less common but potentially serious side effects warrant close monitoring. These include pneumonitis, which is inflammation of the lungs, and hepatotoxicity, indicating liver problems. Progressive Multifocal Leukoencephalopathy (PML), a rare but severe brain infection caused by the JC virus, has been reported and can be fatal. Serious infections, including opportunistic infections, can also occur due to the drug’s effect on the immune system. Acute pancreatitis and other gastrointestinal complications, some with fatal outcomes, have also been reported.
Effective management of side effects often involves close monitoring by the healthcare team, supportive care medications such as anti-nausea drugs, and potentially dose adjustments or temporary interruptions of treatment. Patients are strongly encouraged to communicate any side effects they experience immediately to their healthcare team. This open communication allows for timely intervention, helps mitigate discomfort, and can prevent more serious complications, ensuring the best possible outcome during treatment.