The standard-of-care chemotherapy regimen for patients with previously untreated Hodgkin lymphoma, consisting of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD), has not changed in several decades. Now, data from ECHELON-1, an open-label, randomized phase III clinical trial reveal the superior efficacy of a modified regimen containing the antibody–drug conjugate brentuximab vedotin (A+AVD) instead of bleomycin.
A total of 1,334 patients with stage III or IV previously untreated Hodgkin lymphoma were randomly assigned (1:1) to receive either ABVD or A+AVD. Patients receiving A+AVD had a significant improvement in 2-year modified progression-free survival (82.1% versus 77.2% in the ABVD group; HR 0.77, P = 0.03). Patients receiving A+AVD had an increased risk of grade ≥3 adverse events and neutropenia (83% versus 66%), of which neutropenia was the most frequent (in 54% versus 39% of patients) relative to those in the ABVD group. However, patients in the A+AVD group had a slightly reduced risk of adverse events leading to treatment discontinuation, and fewer deaths during treatment (9 versus 13). Of note, 7 of the 9 deaths in the A+AVD group were neutropenia related, whereas 11 of 13 deaths in the ABVD group involved pulmonary toxicities.
These findings demonstrate the superiority of A+AVD over the current standard-of-care treatment for Hodgkin lymphoma. Patients in the A+AVD group had a higher risk of grade ≥3 neutropenia, leading the trial safety committee to recommend prophylactic use of granulocyte–macrophage colony-stimulating factor to minimize this risk. Investigators also comment that the A+AVD regimen might be substantially safer in elderly patients, who typically have a considerably higher risk of pulmonary toxicities in response to bleomycin.
References
Connors, J. M. et al. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin's lymphoma. N. Engl. J. Med. http://dx.doi.org/10.1056/NEJMoa1708984 (2017)
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Sidaway, P. Brentuximab effective in untreated Hodgkin lymphoma. Nat Rev Clin Oncol 15, 68 (2018). https://doi.org/10.1038/nrclinonc.2017.209
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DOI: https://doi.org/10.1038/nrclinonc.2017.209