FDA Grants Priority Review to Brentuximab Vedotin in Combination With AVD for Frontline Treatment of HL

The U.S. Food and Drug Administration (FDA) granted priority review to a supplemental biologics license application (sBLA) for brentuximab vedotin in combination with AVD (doxorubicin, vinblastine, dacarbazine) as frontline treatment for advanced classical Hodgkin lymphoma (HL).

The sBLA is based on findings from the phase III ECHELON-1 trial that showed brentuximab vedotin plus AVD reduced the risk of disease progression, death, or initiation of new therapy by 23 percent, compared with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy (hazard ratio [HR] = 0.77; 95% CI 0.60-0.98; p=0.03).

From November 19, 2012, through January 13, 2016, 1,344 patients with previously untreated, stage III or IV classical HL were randomized to receive up to six cycles of either ABVD (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.

After a median of 24.9 months follow-up (range not provided), rates of two-year modified progression-free survival (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 adverse events (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.

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.

Brentuximab vedotin previously received breakthrough-therapy designation.

Sources: Seattle Genetics press release, January 2, 2018; Connors JM, Jurczak W, Straus DJ, et al. Brentuximab vedotin plus doxorubicin, vinblastine, dacarbazine (A+AVD) as frontline therapy demonstrates superior modified progression-free survival versus ABVD in patients with previously untreated stage III or IV Hodgkin lymphoma (HL): the phase 3 Echelon-1 study. Abstract #6. Presented at the 2017 American Society of Hematology Annual Meeting, December 10, 2017; Atlanta, GA.