The US Food and Drug Administration has approved brentuximab vedotin to treat adult patients with previously untreated stage III or IV classical Hodgkin lymphoma (cHL) in combination with chemotherapy.

Approval was based on a randomized, open-label, two-arm, multicenter trial, ECHELON-1, that randomized 1,334 patients to receive either brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (AAVD) or bleomycin plus AVD (ABVD).

Patients were randomized to receive up to 6 cycles of AAVD or ABVD on Days 1 and 15 of each 28-day cycle.

Efficacy was established based on modified progression-free survival (mPFS), defined as progression, death, or receipt of additional anticancer therapy for patients who are not in a complete response after completion of frontline therapy.

The estimated median mPFS was not reached in either arm, with a median follow-up time of 24.6 months.

There were 117 events (18%) on the AAVD arm and 146 events (22%) on the ABVD arm (hazard ratio 0.77; 95% CI: 0.60, 0.98; p=0.035), corresponding to a 23 percent reduction in the risk of an mPFS event.

At the time of the mPFS analysis, an interim overall survival analysis did not demonstrate a significant difference.

The most common adverse reactions in at least 20% of patients treated with brentuximab vedotin across all clinical trials were neutropenia, anaemia, peripheral sensory neuropathy, nausea, fatigue, constipation, diarrhoea, vomiting, and pyrexia.

Primary G-CSF prophylaxis is recommended with brentuximab vedotin plus chemotherapy for the frontline treatment of stage III or IV cHL.

The recommended dose of brentuximab vedotin in combination with chemotherapy for previously untreated stage III or IV cHL is 1.2 mg/kg as an intravenous infusion up to a maximum of 120 mg every 2 weeks for 12 doses.

Source: FDA