Nivolumab+AVD in Advanced-Stage Classic Hodgkin's Lymphoma.
Humans
Hodgkin Disease
/ drug therapy
Nivolumab
/ therapeutic use
Male
Female
Adult
Vinblastine
/ therapeutic use
Brentuximab Vedotin
/ therapeutic use
Dacarbazine
/ therapeutic use
Adolescent
Progression-Free Survival
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Middle Aged
Young Adult
Doxorubicin
/ therapeutic use
Aged
Neoplasm Staging
Intention to Treat Analysis
Kaplan-Meier Estimate
Child
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
17 Oct 2024
17 Oct 2024
Historique:
medline:
16
10
2024
pubmed:
16
10
2024
entrez:
16
10
2024
Statut:
ppublish
Résumé
Incorporating brentuximab vedotin into the treatment of advanced-stage classic Hodgkin's lymphoma improves outcomes in adult and pediatric patients. However, brentuximab vedotin increases the toxic effects of treatment in adults, more than half of pediatric patients who receive the drug undergo consolidative radiation, and relapse remains a challenge. Programmed death 1 blockade is effective in Hodgkin's lymphoma, including in preliminary studies involving previously untreated patients. We conducted a phase 3, multicenter, open-label, randomized trial involving patients at least 12 years of age with stage III or IV newly diagnosed Hodgkin's lymphoma. Patients were randomly assigned to receive brentuximab vedotin with doxorubicin, vinblastine, and dacarbazine (BV+AVD) or nivolumab with doxorubicin, vinblastine, and dacarbazine (N+AVD). Prespecified patients could receive radiation therapy directed to residual metabolically active lesions. The primary end point was progression-free survival, defined as the time from randomization to the first observation of progressive disease or death from any cause. Of 994 patients who underwent randomization, 970 were included in the intention-to-treat population for efficacy analyses. At the second planned interim analysis, with a median follow-up of 12.1 months, the threshold for efficacy was crossed, indicating that N+AVD significantly improved progression-free survival as compared with BV+AVD (hazard ratio for disease progression or death, 0.48; 99% confidence interval [CI], 0.27 to 0.87; two-sided P = 0.001). Owing to the short follow-up time, we repeated the analysis with longer follow-up; with a median follow-up of 2.1 years (range, 0 to 4.2 years), the 2-year progression-free survival was 92% (95% CI, 89 to 94) with N+AVD, as compared with 83% (95% CI, 79 to 86) with BV+AVD (hazard ratio for disease progression or death, 0.45; 95% CI, 0.30 to 0.65). Overall, 7 patients received radiation therapy. Immune-related adverse events were infrequent with nivolumab; brentuximab vedotin was associated with more treatment discontinuation. N+AVD resulted in longer progression-free survival than BV+AVD in adolescents and adults with stage III or IV advanced-stage classic Hodgkin's lymphoma and had a better side-effect profile. (Funded by the National Cancer Institute of the National Institutes of Health and others; S1826 ClinicalTrials.gov number, NCT03907488.).
Sections du résumé
BACKGROUND
BACKGROUND
Incorporating brentuximab vedotin into the treatment of advanced-stage classic Hodgkin's lymphoma improves outcomes in adult and pediatric patients. However, brentuximab vedotin increases the toxic effects of treatment in adults, more than half of pediatric patients who receive the drug undergo consolidative radiation, and relapse remains a challenge. Programmed death 1 blockade is effective in Hodgkin's lymphoma, including in preliminary studies involving previously untreated patients.
METHODS
METHODS
We conducted a phase 3, multicenter, open-label, randomized trial involving patients at least 12 years of age with stage III or IV newly diagnosed Hodgkin's lymphoma. Patients were randomly assigned to receive brentuximab vedotin with doxorubicin, vinblastine, and dacarbazine (BV+AVD) or nivolumab with doxorubicin, vinblastine, and dacarbazine (N+AVD). Prespecified patients could receive radiation therapy directed to residual metabolically active lesions. The primary end point was progression-free survival, defined as the time from randomization to the first observation of progressive disease or death from any cause.
RESULTS
RESULTS
Of 994 patients who underwent randomization, 970 were included in the intention-to-treat population for efficacy analyses. At the second planned interim analysis, with a median follow-up of 12.1 months, the threshold for efficacy was crossed, indicating that N+AVD significantly improved progression-free survival as compared with BV+AVD (hazard ratio for disease progression or death, 0.48; 99% confidence interval [CI], 0.27 to 0.87; two-sided P = 0.001). Owing to the short follow-up time, we repeated the analysis with longer follow-up; with a median follow-up of 2.1 years (range, 0 to 4.2 years), the 2-year progression-free survival was 92% (95% CI, 89 to 94) with N+AVD, as compared with 83% (95% CI, 79 to 86) with BV+AVD (hazard ratio for disease progression or death, 0.45; 95% CI, 0.30 to 0.65). Overall, 7 patients received radiation therapy. Immune-related adverse events were infrequent with nivolumab; brentuximab vedotin was associated with more treatment discontinuation.
CONCLUSIONS
CONCLUSIONS
N+AVD resulted in longer progression-free survival than BV+AVD in adolescents and adults with stage III or IV advanced-stage classic Hodgkin's lymphoma and had a better side-effect profile. (Funded by the National Cancer Institute of the National Institutes of Health and others; S1826 ClinicalTrials.gov number, NCT03907488.).
Identifiants
pubmed: 39413375
doi: 10.1056/NEJMoa2405888
doi:
Substances chimiques
Nivolumab
31YO63LBSN
Vinblastine
5V9KLZ54CY
Brentuximab Vedotin
7XL5ISS668
Dacarbazine
7GR28W0FJI
Doxorubicin
80168379AG
Banques de données
ClinicalTrials.gov
['NCT03907488']
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Clinical Trial, Phase III
Comparative Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
1379-1389Subventions
Organisme : NIH HHS
ID : U10CA180819
Pays : United States
Organisme : NIH HHS
ID : U10CA180820
Pays : United States
Organisme : NIH HHS
ID : U10CA180821
Pays : United States
Organisme : NIH HHS
ID : U10CA180863
Pays : United States
Organisme : NIH HHS
ID : U10CA180888
Pays : United States
Organisme : NIH HHS
ID : UG1CA189955
Pays : United States
Informations de copyright
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