FDA Greenlights Adcetris as First-line Combination Therapy for Classical Hodgkin Lymphoma

Today, the FDA expanded the approval of brentuximab vedotin (Adcetris) to include treatment-naïve adults with stage 3 or 4 classical Hodgkin lymphoma (cHL), in combination with chemotherapy, according to a press release.

Brentuximab vedotin combines an antibody and a drug that targets CD30 on lymphoma cells. The FDA previously authorized brentuximab vedotin to treat cHL after relapse and after stem cell transplant in high-risk patients. Additionally, the drug is approved to treat systemic anaplastic large cell lymphoma (ALCL) after treatment failure and primary cutaneous ALCL after treatment failure.

The new approval for adults with cHL was based on clinical trial findings that compared brentuximab vedotin plus chemotherapy (Adriamycin [doxorubicin], vinblastine and dacarbazine [AVD]) with chemotherapy alone.

The study investigated modified progression-free survival, which measured time to disease progression, death, or new treatment among patients who did not achieve a complete response, according to the release.

After an average of six 28-day cycles of therapy, patients administered brentuximab vedotin plus AVD were 23% less likely to experience progression, death, or initiation of a new therapy compared with those receiving chemotherapy alone, according to the FDA.

Only 18% patients in the combination therapy cohort experienced disease progression, death, or started a new therapy compared with 22% of the chemotherapy cohort.

Common adverse effects included neutropenia, anemia, peripheral neuropathy, nausea, fatigue, constipation, diarrhea, vomiting, and pyrexia.

In the trial, 67% of patients treated with brentuximab vedotin plus chemotherapy experienced peripheral neuropathy and 91% of patients experienced neutropenia, according to the release.

The FDA advised that preventative treatment with G-CSF is recommended with brentuximab vedotin plus chemotherapy for cHL.

Brentuximab vedotin comes with a boxed warning for the risk of John Cunningham virus infection resulting in progressive multifocal leukoencephalopathy, according to the FDA.

Patients with cHL have abnormal lymphocytes in the lymph nodes, but with early treatment, patients can typically achieve remission, according to the FDA. Current estimates indicate that 8260 Americans were diagnosed with Hodgkin lymphoma in 2017, with more than 1000 dying from the disease.

“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 Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA 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.”