Medication Monitor

Generic Name (Trade Name—Company)
March 26, 2018

Brentuximab vedotin

(Adcetris—Seattle Genetics)
Approval expanded for first-line treatment of Stage III or IV classical Hodgkin lymphoma in combination with chemotherapy

FDA expanded the approval of brentuximab vedotin for treatment of adults with previously untreated Stage III or IV classical Hodgkin lymphoma (cHL) in combination with chemotherapy.

The agent was previously approved 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.

Brentuximab vedotin combines an antibody and drug, allowing the antibody to direct the drug to a target on lymphoma cells known as CD30.

Approval for this indication was based on a clinical trial comparing the agent plus chemotherapy (Doxorubicin [Adriamycin], 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 (mPFS), 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% less likely to experience progression, death, or initiation of new therapy compared with those receiving ABVD.

A total of 117 (18%) patients were in the brentuximab vedotin plus AVD arm who experienced disease progression, death, or began new therapy, compared with 146 (22%) of patients in the ABVD arm.

Common adverse effects include neutropenia, anemia, peripheral neuropathy, nausea, fatigue, constipation, diarrhea, vomiting, and fever. In the above clinical trial, 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 (neutropenia and fever). Preventive treatment with G-CSF, a growth factor for the bone marrow to produce white blood cells, is recommended with brentuximab vedotin plus chemotherapy for first-line treatment of Stage III or IV cHL.

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