The FDA has expanded the approval of brentuximab vedotin (Adcetris®, Seattle Genetics, Inc.) in combination with chemotherapy as a first-line treatment for adults with systemic anaplastic large cell lymphoma (ALCL) and other peripheral T-cell lymphomas (PTCLs) expressing the tumor marker CD30. This is the first FDA-approved treatment for patients with newly diagnosed PTCLs.
Peripheral T-cell lymphomas are a diverse group of rare non-Hodgkin lymphomas that result when the immune system's T cells develop abnormally. Although they can occur at any time during adulthood, PTCLs typically arise in individuals over the age of 60. They are aggressive and difficult to treat.
"The current standard of care for initial treatment of peripheral T-cell lymphoma is multi-agent chemotherapy. That treatment has not significantly changed in decades and is too often unsuccessful in leading to long-term remissions, underscoring the need for new treatments," commented Steven Horwitz, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center.
Brentuximab vedotin is a monoclonal antibody that binds to CD30, also known as TNFRSF8, a cell membrane protein of the tumor necrosis factor receptor family. It was previously approved for adults with treatment-naive stage III or IV classical Hodgkin lymphoma (cHL), relapsed cHL, post-stem cell transplant cHL with high risk of relapse or progression, refractory systemic ALCL, refractory primary cutaneous ALCL, and refractory CD30-expressing mycosis fungoides.
This approval was based on the ECHELON-2 trial (NCT01777152), in which 452 patients with CD30-positive ALCL, non-Hodgkin lymphoma, or T-cell lymphoma were randomized to receive brentuximab vedotin plus cyclophosphamide/doxorubicin/prednisone (CHP) or a chemotherapy regimen of cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) alone. Brentuximab vedotin plus CHP improved median progression-free survival compared with CHOP (48 vs 21 months). It also improved median overall survival and overall response rates.
The most common side effects of brentuximab vedotin in combination with chemotherapy included peripheral neuropathy, nausea and vomiting, diarrhea, low white blood cell count, fatigue, mouth sores, constipation, hair loss, fever, and anemia.
Patients should be monitored for infusion reactions, anaphylaxis, neuropathy, fever, gastrointestinal complications, and infections, in addition to tumor lysis syndrome, serious skin reactions, pulmonary toxicity, and hepatotoxicity. The prescribing information contains a boxed warning concerning the risk of progressive multifocal leukoencephalopathy, a potentially fatal infection of the brain. Brentuximab vedotin is contraindicated for women who are pregnant or breastfeeding.
For More Information
Clinicaltrials.gov (2018). ECHELON-2: a comparison of brentuximab vedotin and CHP with standard-of-care CHOP in the treatment of patients with CD30-positive mature T-cell lymphomas (ECHELON-2). NLM identifier: NCT01777152.