Brentuximab Vedotin Combo Lowers Risk of Death in Patients With Hodgkin Lymphoma

Combination therapy with brentuximab vedotin (Adcetris) plus doxorubicin, vinblastine, and dacarbazine (A+AVD) produced a significant decrease in the risk of death compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in patients with previously untreated stage III/IV classical Hodgkin lymphoma, according to a presentation at the American Society of Clinical Oncology (ASCO) 2022 annual meeting.¹

Six-year follow-up data from the phase 3 ECHELON-1 trial (NCT01712490) also showed a manageable safety profile for the A+AVD combination consistent with previous findings in patients with stage III/IV classical Hodgkin lymphoma.

At a median follow-up of 73 months, estimated overall survival (OS) rates were 93.9% (95% CI, 91.6%-95.5%) with the A+AVD combination compared with 89.4% (95% CI, 86.6%-91.7%) in the cohort administered ABVD (HR 0.59; 95% CI, 0.40-0.88; P = .009). Median OS has not yet been reached in either cohort.

“Brentuximab vedotin plus AVD is the first regimen to show an improvement in OS compared with standard ABVD chemotherapy in patients with previously untreated, advanced stage classical Hodgkin lymphoma,” said lead study author Stephen Ansell, MD, PhD, professor of medicine, consultant, and chair of Faculty Development and Recruitment in the Division of Hematology and Department of Internal Medicine at Mayo Clinic, in a presentation on the findings at ASCO. “Based on these data, AVD chemotherapy plus brentuximab vedotin should be considered a preferred first-line treatment in patients with previously untreated, advanced stage classical Hodgkin lymphoma.”

The trial randomized 1334 patients 1:1 to receive up to 6 cycles of A+AVD (n = 664) or ABVD (n = 670) intravenously on days 1 and 15 every 28 days. The trial achieved its primary end point of modified progression-free survival (PFS) per independent review committee, with 5-year follow-up data supporting a long-term PFS benefit with first-line A+AVD compared with ABVD in patients with stage III/IV classical Hodgkin lymphoma, independent of interim positron emission tomography (PET) status.²

Most patients in the trial were male (n = 776; 58%) and the median age was 36 years (range, 26-52). Most patients were under 60 years of age (n = 1148; 86%), had Ann Arbor stage IV disease at the time of diagnosis (n = 846; 64%), had an International Prognostic Score of 2 or 3 (n = 712; 53%), and had negative PET2 status (n = 1166; 87%).

At the data cutoff of June 1, 2021, 39 OS events were reported in the A+AVD cohort compared with 64 OS events in the ABVD cohort.

The results also showed a consistent OS benefit with A+AVD compared with ABVD across prespecified subgroups, according to the investigators. Age, non-White race, ECOG performance status, and PET2 status had the greatest association with OS, according to the findings.

Six-year PFS estimates in the A+AVD cohort were 82.3% (95% CI, 79.1%-85.0%) compared with 74.5% (95% CI, 70.8%-77.7%) in the ABVD cohort. There were 112 PFS events in the A+AVD cohort compared with 159 PFS events in the ABVD cohort.

There were no new safety signals identified, with A+AVD showing a comparable long-term safety profile to ABVD. Fewer patients died from Hodgkin lymphoma and disease- or treatment-related complications in the A+AVD cohort (n = 39; 5.9%) compared with the ABVD (n = 64; 9.7%) cohort.

Further, there were fewer second malignancies in the A+AVD cohort (n = 23; hematologic malignancies, n = 9; solid tumors, n = 14) compared with the ABVD cohort (n = 32; hematologic malignancies, n = 17; solid tumors, n = 14), which matches prior findings. Two patients with second malignancies in each cohort underwent transplant and 3 patients in the ABVD group received prior radiation.

“A+AVD improved OS vs ABVD despite the wide availability and use of active salvage treatment, including substantial use of subsequent brentuximab vedotin in the ABVD arm. The OS benefit with A+AVD was coupled with fewer second malignancies vs ABVD,” Ansell said. “The observed OS benefit with A+AVD, fewer disease-related deaths, and a concomitant reduction in disease progression, suggests that A+AVD has potentially cured more patients of their disease.”

References

1. Ansell SM, Connors JM, Radford JA, et al. 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. J Clin Oncol. 2022;40(suppl 16):7503. doi:10.1200/JCO.2022.40.16_suppl.7503
2. Straus DJ, Dlugosz-Danecka M, Connors JM, et al. Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5-year update of an international, open-label, randomised, phase 3 trial. Lancet Hematol. 2021;8(6);e410-e421. doi:10.1016/S2352-3026(21)00102-2