Nivolumab+AVD in Advanced-Stage Classic Hodgkin's Lymphoma.

in The New England journal of medicine by Alex F Herrera, Michael LeBlanc, Sharon M Castellino, Hongli Li, Sarah C Rutherford, Andrew M Evens, Kelly Davison, Angela Punnett, Susan K Parsons, Sairah Ahmed, Carla Casulo, Nancy L Bartlett, Joseph M Tuscano, Matthew G Mei, Brian T Hess, Ryan Jacobs, Hayder Saeed, Pallawi Torka, Boyu Hu, Craig Moskowitz, Supreet Kaur, Gaurav Goyal, Christopher Forlenza, Andrew Doan, Adam Lamble, Pankaj Kumar, Saeeda Chowdhury, Brett Brinker, Namita Sharma, Avina Singh, Kristie A Blum, Anamarija M Perry, Alexandra Kovach, David Hodgson, Louis S Constine, Lale Kostakoglu Shields, Anca Prica, Hildy Dillon, Richard F Little, Margaret A Shipp, Michael Crump, Brad Kahl, John P Leonard, Sonali M Smith, Joo Y Song, Kara M Kelly, Jonathan W Friedberg

TLDR

  • The study found that nivolumab plus AVD significantly improved progression-free survival compared to brentuximab vedotin plus AVD in patients with advanced-stage classic Hodgkin's lymphoma.
  • The study suggests that nivolumab-based therapy may be a more effective and safer treatment option for this patient population.
  • The findings may lead to the development of new combination therapies that integrate immunotherapy with chemotherapy or radiation therapy in the treatment of Hodgkin's lymphoma.

Abstract

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.).

Overview

  • The study aimed to compare the efficacy and safety of brentuximab vedotin (BV) with nivolumab (N) in combination with AVD in patients with stage III or IV newly diagnosed Hodgkin's lymphoma.
  • The study included 970 patients in the intention-to-treat population, with a median follow-up of 12.1 months and a range of 0 to 4.2 years.
  • The primary objective of the study was to determine the superiority of N+AVD over BV+AVD in terms of progression-free survival (PFS) in patients with advanced-stage classic Hodgkin's lymphoma.

Comparative Analysis & Findings

  • The study found that N+AVD significantly improved PFS compared to BV+AVD (hazard ratio, 0.48; 99% CI, 0.27 to 0.87; P = 0.001) at the second planned interim analysis.
  • With a median follow-up of 2.1 years, the 2-year PFS was 92% (95% CI, 89 to 94) with N+AVD and 83% (95% CI, 79 to 86) with BV+AVD.
  • Immune-related adverse events were infrequent with nivolumab, while brentuximab vedotin was associated with more treatment discontinuation.

Implications and Future Directions

  • The study suggests that nivolumab-based therapy may be a more effective and safer treatment option for patients with advanced-stage classic Hodgkin's lymphoma.
  • Future studies should investigate the optimal duration of nivolumab treatment and the incorporation of nivolumab in combination with other therapies for Hodgkin's lymphoma.
  • The study's findings may also lead to the development of new combination therapies that integrate immunotherapy with chemotherapy or radiation therapy in the treatment of Hodgkin's lymphoma.
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