FDA Expands Approval of Brentuximab Vedotin in Classical Hodgkin Lymphoma

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ON MARCH 20, the U.S. Food and Drug Administration (FDA) approved brentuximab vedotin (Adcetris), an antibody-drug conjugate, to treat adult patients with previously untreated stage III or IV classical Hodgkin lymphoma in combination with chemotherapy. Brentuximab vedotin combines an antibody and drug and acts by targeting CD30 on lymphoma cells. 

ECHELON-1 Trial 

THE APPROVAL for adult patients with previously untreated stage III or IV classical Hodgkin lymphoma was based on the ECHELON-1 clinical trial ( Identifier NCT01712490), which compared 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. Results of the trial were presented at the 2018 American Society of Hematology Annual Meeting & Exposition and recently published.1,2 

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 disease progression, death, or initiation of new therapy compared with those receiving ABVD. There were 117 patients (18%) on the brentuximab vedotin– plus-AVD arm who experienced disease progression, death, or began new therapy, compared to 146 patients (22%) on the ABVD arm. 

Safety and Toxicity 

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. Preventive treatment with granulocyte colony-stimulating factor 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 hepatic 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. 

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 disease progression; systemic anaplastic large cell lymphoma (ALCL) after failure of other treatment; and primary cutaneous ALCL after failure of other treatment. ■


1. Connors JM, et al: 2017 ASH Annual Meeting. Abstract 6. Presented December 10, 2017. 

2. Connors JM, et al: N Engl J Med 378:331-344, 2018.