The FDA expanded the approval of brentuximab vedotin to include the treatment of adult patients with previously untreated stage III or IV classical Hodgkin lymphoma (cHL) in combination with AVD (doxorubicin, vinblastine, dacarbazine).
The approval was based on results from the phase III ECHELON-1 clinical trial. From November 19, 2012, through January 13, 2016, 1,344 patients with previously untreated stage III or IV cHL were randomized to receive up to six cycles of either ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine; n=670) or brentuximab vedotin plus AVD (n=664). The median age was 36 years (range = 18-83 years), 64 percent of patients in each group had stage IV disease, and 58 percent in each group had B symptoms.
Treatment with brentuximab vedotin plus AVD reduced the risk of disease progression, death, or initiation of new therapy by 23 percent, compared with ABVD (HR=0.77; 95% CI 0.60-0.98; p=0.03).
After a median follow-up of 24.9 months (range not provided), rates of two-year modified PFS were significantly higher in the brentuximab vedotin plus AVD group: 82.1 percent (95% CI 78.7-85.0) versus 77.2 percent (95% CI 73.7-80.4).
The most common AEs in each arm were neutropenia, constipation, vomiting, fatigue, and peripheral neuropathy. Pulmonary toxicity was more frequent and severe with ABVD (3% vs. <1%), but neutropenia and peripheral neuropathy were more common in the brentuximab vedotin plus AVD arm.
Eighty-eight (13%) and 105 (16%) patients, respectively, discontinued treatment because of AEs. Serious AEs included peripheral neuropathy; anaphylaxis; infusion-site reactions; hematologic, pulmonary, and hepato-toxicities; serious infections; tumor lysis syndrome; serious dermatologic reactions; and gastrointestinal complications.
There were 22 on-treatment deaths; seven of nine deaths (78%) in the brentuximab vedotin plus AVD group were associated with neutropenia, and 11 of 13 (85%) in the ABVD group were associated with pulmonary toxicity.
The drug has a boxed warning for the risk of JC virus infection resulting in progressive multifocal leukoencephalopathy, a rare but serious brain infection that can be fatal.
Brentuximab vedotin previously received priority review and breakthrough-therapy designation for this indication. The drug also previously received FDA approval for relapsed cHL, cHL after HCT in patients at high risk of relapse or progression, and previously treated systemic and primary cutaneous anaplastic large-cell lymphoma.
Source: U.S. Food and Drug Administration press release, March 20, 2018.