FDA Expands Approval of Brentuximab Vedotin for First-Line Treatment of Stage III or IV Classical Hodgkin Lymphoma in Combination With Chemotherapy

On March 20, the U.S. Food and Drug Administration (FDA) approved brentuximab vedotin (Adcetris) to treat adult patients with previously untreated stage III or IV classical Hodgkin lymphoma in combination with chemotherapy.

“Today’s approval represents an improvement in the initial treatment regimens of advanced Hodgkin lymphoma that were introduced into clinical practice more than 40 years ago,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “This approval demonstrates our commitment to approving advancements in treatment that give prescribers and patients different options for care.”

Brentuximab vedotin combines an antibody and drug, allowing the antibody to direct the drug to a target on lymphoma cells known as CD30. Brentuximab vedotin has also been previously approved by the FDA to treat classical Hodgkin lymphoma after relapse; classical Hodgkin lymphoma after stem cell transplant when a patient is at a high risk of relapse or progression; systemic anaplastic large cell lymphoma (ALCL) after failure of other treatment; and primary cutaneous ALCL after failure of other treatment.

ECHELON-1 Trial

The approval for adult patients with previously untreated stage III or IV classical Hodgkin lymphoma was based on the ECHELON-1 trial, which is comparing brentuximab vedotin plus chemotherapy (doxorubicin, vinblastine, and dacarbazine [AVD]) to a chemotherapy-only regimen common for classical Hodgkin lymphoma treatment (AVD plus bleomycin [ABVD]). The trial measured modified progression-free survival. ECHECLON-1 results were presented at the 2017 American Society of Hematology Annual Meeting and Exposition and published in The New England Journal of Medicine.

In the trial of 1,334 patients, after patients received an average of six 28-day cycles of treatment, those treated with brentuximab vedotin plus AVD were 23% less likely to experience progression, death, or initiation of new therapy compared with those receiving ABVD. There were 117 (18%) patients on the brentuximab vedotin plus AVD arm who experienced disease progression, death, or began new therapy, compared to 146 (22%) patients on the ABVD arm.

Adverse Events and Safety

Common side effects of brentuximab vedotin include neutropenia, anemia, peripheral neuropathy, nausea, fatigue, constipation, diarrhea, vomiting, and pyrexia. In ECHELON-1, 67% of patients treated with brentuximab vedotin plus chemotherapy experienced peripheral neuropathy. In addition, neutropenia occurred in 91% of patients treated with brentuximab vedotin plus chemotherapy, which was associated with a 19% rate of febrile neutropenia. Preventative treatment with granulocyte colony-stimulating factor, a growth factor for the bone marrow to produce white blood cells, is recommended with brentuximab vedotin plus chemotherapy for the first-line treatment of stage III or IV classical Hodgkin lymphoma.

Brentuximab vedotin has a boxed warning that highlights the risk of John Cunningham virus infection resulting in progressive multifocal leukoencephalopathy, a rare but serious brain infection that can result in death.

Serious risks of brentuximab vedotin include peripheral neuropathy; severe anaphylaxis or infusion-site reactions; hematologic, pulmonary, and hepato-toxicities; serious or opportunistic infections; tumor lysis syndrome; serious dermatologic reactions; and gastrointestinal complications. Brentuximab vedotin can cause harm to a developing fetus and newborn baby; women should be advised of the potential risk to the fetus and to use effective contraception, and to avoid breastfeeding while on treatment.

The FDA granted this application Priority Review and Breakthrough Therapy designations. 

The FDA granted the approval to Seattle Genetics, Inc.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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