Steven Ansell, MD, PhD, Professor of Medicine at Mayo Clinic. In this video, he speaks about the ASCO Abstract – First-line brentuximab vedotin plus chemotherapy to improve overall survival in patients with stage III/IV classical Hodgkin lymphoma: An updated analysis of ECHELON-1.
Origins:
To date, an overall survival (OS) benefit from innovative therapy combinations over conventional treatments in first-line classical Hodgkin lymphoma has seldom been demonstrated (cHL). The development of more active medicines for relapsed/refractory illness has made demonstrating increased OS with first-line therapy difficult. In ECHELON-1 (NCT01712490), 5-year follow-up studies supported the long-term progression-free survival (PFS) benefit of first-line brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in patients with stage III/IV A+AVD had a reasonable long-term safety profile, with fewer second malignancies and a higher number of pregnancies observed compared to ABVD (Connors et al, NEJM 2018; Straus et al, Lancet Haematol 2021). After approximately 6 years of follow-up, we present a prespecified OS analysis (cut-off, June 1, 2021).
Methodology:
Pts were randomly assigned to one of six cycles of A+AVD (n = 664) or ABVD (n = 670) on day one and 15 every 28 days. The primary secondary endpoint was OS, which was an event-driven, pre-specified, alpha-controlled study in an intention-to-treat sample.
Outcomes:
At a median follow-up of 73 months, 39 and 64 OS incidents occurred in the A+AVD and ABVD arms, respectively: OS favored A+AVD over ABVD (HR 0.590; 95 percent CI 0.396"“0.879; p = 0.009). Estimated 6-year OS rates (95 percent CI) for A+AVD vs ABVD were 93.9 percent (91.6"“95.5) vs 89.4 percent (86.6"“91.7), respectively. Across prespecified subgroups, there was a consistent OS advantage for A+AVD vs ABVD. The 6-year PFS estimate for A+AVD vs ABVD was 82.3 percent (79.1"“85.0) vs 74.5 percent (70.8"“77.7) (HR 0.678 [95 percent CI 0.532"“0.863]). Overall, A+AVD showed a long-term safety profile similar to ABVD. Treatment-emergent peripheral neuropathy improved or resolved in both arms, with 86 percent (379/443) and 87 percent (249/286) of cases in the A+AVD and ABVD arms either entirely resolving (72 percent vs 79 percent) or improving (14 percent vs 8 percent) by the last follow-up. There were fewer second malignancies reported in the A+AVD arm compared to the ABVD arm (23 vs 32). Female patients in the A+AVD arm reported more pregnancy (49 vs 28) or live births (42 vs 19 in females) than in the ABVD arm; no stillbirths were observed. There were no new safety signals discovered.
Observations:
Treatment with A+AVD resulted in a statistically significant 41 percent reduction in the risk of death compared to ABVD, with a manageable safety profile similar with previous studies. These findings support A+AVD as a treatment option for patients with previously untreated stage III/IV cHL. NCT01712490 is the clinical trial number.