Oct. 27, 2022
A follow-up of the previously reported ECHELON-1 trial showed favorable outcomes related to overall survival for Hodgkin lymphoma. The multicenter, randomized, open-label trial evaluated patients with stage 3 or stage 4 Hodgkin lymphoma. The two treatment arms included:
- Standard treatment of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD)
- A new treatment option brentuximab vedotin plus doxorubicin, vinblastine and dacarbazine (A+AVD)
Initial results of the ECHELON-1 trial were reported in the New England Journal of Medicine in 2018 and discussed the study's primary end point of modified progression-free survival. The study's key secondary end point was overall survival. The five-year follow-up showed improved overall survival for patients who received A+AVD. These results were reported in the July 2022 edition of the New England Journal of Medicine.
"This is the first time we've moved the needle on survival for Hodgkin lymphoma," says Stephen M. Ansell, M.D., Ph.D., a hematologist and oncologist for Mayo Clinic Comprehensive Cancer Center in Rochester, Minnesota, and the study's lead author. Dr. Ansell also is the chair of Hematology and was named senior deputy director, Midwest, for the Cancer Center in June 2022.
Overall survival for ECHELON-1
Participants in the study were randomly assigned in a 1-1 ratio so that 664 patients received treatment with A+AVD and 670 patients received treatment with ABVD. The patients underwent up to six cycles of treatment. Both treatments were administered intravenously on days 1 and 15 of each 28-day cycle. Most patients completed all six cycles, 593 in the A+AVD group and 608 in the ABVD group.
The median follow-up for overall survival was 73 months. In the group receiving A+AVD, 39 patients died, for an overall survival rate of 93.9%. In the group receiving ABVD, 64 patients died, for an overall survival rate of 89.4%.
"The impact on overall survival with brentuximab vedotin plus AVD chemotherapy is somewhat surprising," says Dr. Ansell. "It does confirm that the use of novel agents in the frontline treatment of patients with Hodgkin lymphoma has a long-term impact."
In addition to improved overall survival with A+AVD, fewer patients in that group received subsequent therapy and fewer second cancers were reported. In the A+AVD group, 20.4% of patients received subsequent therapy, including transplantation, and 23 patients reported second cancers. In the ABVD group, 23.8% patients received subsequent therapy, including transplantation, and 32 patients reported second cancers.
Manageable toxicities among treatments
With the addition of new drugs comes concerns regarding toxicities and long-term side effects. Fertility was not formally assessed, but the number of pregnancies was reported in the follow-up study. A total of 195 pregnancies were reported, 114 of which occurred in the patients or partners of patients in the A+AVD group and 81 in the ABVD group.
A higher incidence of both febrile neutropenia and peripheral neuropathy were reported in the A+AVD group. The incidence of febrile neutropenia was lower and similar to that of the ABVD group with the addition of granulocyte colony-stimulating factor primary prophylaxis. More pulmonary toxicity was seen in the ABVD group.
A total of 443 patients in the A+AVD group and 286 patients in the ABVD group experienced peripheral neuropathy. Most patients, 85.6% in the A+AVD group, had complete resolution or amelioration of their symptoms by final follow up.
"Overall, the toxicities in both arms of the trial were comparable," says Dr. Ansell. "We were somewhat surprised to see a decrease in secondary cancers among the brentuximab vedotin plus AVD group and pleased to note that many of the toxicities were resolved by the end of the follow-up period."
For more information
Connors JM, et al. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin's lymphoma. New England Journal of Medicine. 2018;378:331.
Ansell SM, et al. Overall survival with brentuximab vedotin in stage III or IV Hodgkin's lymphoma. New England Journal of Medicine. 2022;387:310.
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