First-Line Brentuximab Vedotin Lowers Risk of Death in Classical Hodgkin Lymphoma: ECHELON-1

Brentuximab vedotin, a CD30-directed antibody-drug conjugate, plus doxorubicin, vinblastine, and dacarbazine (AVD) provides a long-term survival advantage vs standard doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for the first-line treatment of patients with stage III or IV classical Hodgkin lymphoma, according to results from the ECHELON-1 trial.

“In this trial involving patients with previously untreated stage III or IV Hodgkin’s lymphoma, treatment with [brentuximab vedotin plus] AVD resulted in a risk of death that was significantly lower by 41% than that observed with ABVD therapy,” wrote Stephen M. Ansell, MD, Division of Hematology, Mayo Clinic, Rochester, MN, and colleagues, adding, “This result translated to an overall difference in mortality of 4.5 percentage points in favor of [brentuximab vedotin plus] AVD at 6 years.”

The primary end point of the ECHELON-1 trial was modified progression-free survival (PFS), which has been previously reported. Overall survival (OS) in the intention-to-treat population was a key secondary end point. A planned interim analysis indicated a potential benefit with regard to OS; data from a median of 6 years of follow-up are reported here.

The trial randomized 1334 patients in a 1:1 ratio to receive up to 6 cycles of brentuximab vedotin plus AVD (n = 664) or ABVD (n = 670). At a median follow-up of 73 months, 39 patients in the brentuximab vedotin plus AVD arm and 64 patients in the ABVD arm had died (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.40 to 0.88; P = .009).

The 6-year OS estimates were 93.9% (95% CI, 91.6 to 95.5) in the brentuximab vedotin plus AVD arm and 89.4% (95% CI, 86.6 to 91.7) in the ABVD arm. In addition, PFS was longer with brentuximab vedotin plus AVD vs ABVD (HR for disease progression or death, 0.68; 95% CI, 0.53 to 0.86).

Overall, fewer patients in the brentuximab vedotin plus AVD arm received subsequent therapy, including transplantation, and had fewer second cancers reported than those in the ABVD arm  (23 vs 32 patients).

In the brentuximab vedotin plus AVD arm, an increased incidence of febrile neutropenia was reported and primary prophylaxis with granulocyte colony-stimulating factor was recommended. Overall, more patients experienced peripheral neuropathy in the brentuximab vedotin plus AVD arm vs the ABVD arm. However researchers noted that most patients in the 2 groups had resolution or amelioration of the event by the last follow-up.

“Patients who received [brentuximab vedotin plus] AVD for the treatment of stage III or IV Hodgkin lymphoma had a survival advantage over those who received ABVD,” Dr Ansell and colleagues concluded.

“The treatment of advanced Hodgkin’s lymphoma has been a success story in oncology, but only modest progress has been made in past decades,” they added, “However, in this trial, treatment with [brentuximab vedotin plus] AVD resulted in an improvement in both [PFS] and [OS].”

Source:

Ansell SM, Radford J, Connors JM, et al. Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkin’s Lymphoma. N Engl J Med. 2022;387(4):310-320. doi:10.1056/nejmoa2206125