The Medical Letter on Drugs and Therapeutics
In Brief: Brentuximab Vedotin (Adcetris) for Classical Hodgkin's Lymphoma (online only)
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Med Lett Drugs Ther. 2018 Nov 5;60(1559):e185
 Select a term to see related articles  Adcentris   brentuximab vedotin   dacarbazine   doxorubicin   lymphoma 

The FDA has approved the anti-CD30 antibody-drug conjugate brentuximab vedotin (Adcetris – Seattle Genetics) for use in combination with chemotherapy for IV treatment of adults with previously untreated stage 3 or 4 classical Hodgkin's lymphoma (cHL). Adcetris was approved earlier for consolidation treatment of cHL and for treatment of relapsed or refractory cHL, anaplastic large cell lymphoma, and CD30-expressing mycosis fungoides.

FDA approval for the new indication was based on the results of an open-label trial (ECHELON-1) in 1334 patients with previously untreated stage 3 or 4 cHL.1 Patients were randomized to receive a regimen consisting of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD; standard initial treatment for cHL) or a regimen that included brentuximab vedotin instead of bleomycin (A+AVD). Bleomycin can cause severe pulmonary toxicity and is often dropped from the regimen after several cycles of ABVD.

The 2-year modified progression-free survival rate (the primary endpoint; defined as time to progression, death, or noncomplete response and use of subsequent anticancer therapy) was 82.1% with A+AVD and 77.2% with ABVD, a statistically significant difference.

Neutropenia and peripheral neuropathy were more common with A+AVD than with ABVD (58% vs 45% and 67% vs 43%, respectively). Severe pulmonary toxicity was more common with ABVD (3% vs <1%). Of the 9 deaths that occurred in the A+AVD group, 7 were related to neutropenia; 11 of the 13 deaths in the ABVD group were related to pulmonary toxicity. PET scans to evaluate the response to therapy, which could have permitted discontinuation of bleomycin after the first 2 cycles and decreased the risk of pulmonary toxicity, were not performed.2

Six cycles of A+AVD have been estimated to cost up to $850,000, compared to less than $8000 for ABVD.3 There is no evidence to date that the new regimen improves overall survival in patients with previously untreated stage 3 or 4 cHL.

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