The FDA approved brentuximab vedotin to treat adult patients with previously untreated stage III or IV classical Hodgkin lymphoma (cHL) in combination with chemotherapy.
"[This] 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."
The NCI estimates that 8,260 people in the U.S. were diagnosed with Hodgkin lymphoma last year, and approximately 1,070 patients with non-Hodgkin lymphoma died from the disease in 2017.
Brentuximab vedotin combines an antibody and drug, allowing the antibody to direct the drug to a target on lymphoma cells known as CD30. It has been previously approved by the FDA to treat cHL after relapse, cHL after stem cell transplant when a patient is at 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.
The approval for adult patients with previously untreated stage III/IV cHL was based on a clinical trial comparing brentuximab vedotin plus chemotherapy (doxorubicin, vinblastine, and dacarbazine, or AVD) to a chemotherapy-only regimen common for cHL treatment (AVD plus bleomycin, also known as ABVD). The trial measured modified progression-free survival, which considers the length of time it took for the disease to progress, death to occur, or new therapy to be initiated in patients who did not achieve a complete response.
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 percent 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 beginning new therapy compared to 146 (22%) patients on the ABVD arm.
Common side effects of brentuximab vedotin include neutropenia, anemia, peripheral neuropathy, nausea, fatigue, constipation, diarrhea, vomiting, and pyrexia. In the above clinical trial, 67 percent of patients treated with brentuximab vedotin plus chemotherapy experienced peripheral neuropathy. In addition, neutropenia occurred in 91 percent of patients treated with brentuximab vedotin plus chemotherapy, which was associated with a 19 percent rate of febrile neutropenia. Preventative treatment with G-CSF is recommended with brentuximab vedotin plus chemotherapy for the first-line treatment of stage III/IV cHL.
Brentuximab vedotin has a boxed warning that highlights the risk of John Cunningham virus infection, resulting in progressive multifocal leukoencephalopathy.
The FDA granted this application Priority Review and Breakthrough Therapy designations.