Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma
- PMID: 34986285
- PMCID: PMC9844513
- DOI: 10.1056/NEJMoa2109970
Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma
Abstract
Background: Lymphocyte-activation gene 3 (LAG-3) and programmed death 1 (PD-1) are distinct inhibitory immune checkpoints that contribute to T-cell exhaustion. The combination of relatlimab, a LAG-3-blocking antibody, and nivolumab, a PD-1-blocking antibody, has been shown to be safe and to have antitumor activity in patients with previously treated melanoma, but the safety and activity in patients with previously untreated melanoma need investigation.
Methods: In this phase 2-3, global, double-blind, randomized trial, we evaluated relatlimab and nivolumab as a fixed-dose combination as compared with nivolumab alone when administered intravenously every 4 weeks to patients with previously untreated metastatic or unresectable melanoma. The primary end point was progression-free survival as assessed by blinded independent central review.
Results: The median progression-free survival was 10.1 months (95% confidence interval [CI], 6.4 to 15.7) with relatlimab-nivolumab as compared with 4.6 months (95% CI, 3.4 to 5.6) with nivolumab (hazard ratio for progression or death, 0.75 [95% CI, 0.62 to 0.92]; P = 0.006 by the log-rank test). Progression-free survival at 12 months was 47.7% (95% CI, 41.8 to 53.2) with relatlimab-nivolumab as compared with 36.0% (95% CI, 30.5 to 41.6) with nivolumab. Progression-free survival across key subgroups favored relatlimab-nivolumab over nivolumab. Grade 3 or 4 treatment-related adverse events occurred in 18.9% of patients in the relatlimab-nivolumab group and in 9.7% of patients in the nivolumab group.
Conclusions: The inhibition of two immune checkpoints, LAG-3 and PD-1, provided a greater benefit with regard to progression-free survival than inhibition of PD-1 alone in patients with previously untreated metastatic or unresectable melanoma. Relatlimab and nivolumab in combination showed no new safety signals. (Funded by Bristol Myers Squibb; RELATIVITY-047 ClinicalTrials.gov number, NCT03470922.).
Copyright © 2022 Massachusetts Medical Society.
Figures
Comment in
-
A New Combination Immunotherapy in Advanced Melanoma.N Engl J Med. 2022 Jan 6;386(1):91-92. doi: 10.1056/NEJMe2116892. N Engl J Med. 2022. PMID: 34986291 No abstract available.
-
LAG3 inhibition improves outcomes.Nat Rev Clin Oncol. 2022 Mar;19(3):149. doi: 10.1038/s41571-022-00602-8. Nat Rev Clin Oncol. 2022. PMID: 35031714 No abstract available.
-
CTLA-4 Blockade Resistance after Relatlimab and Nivolumab.N Engl J Med. 2022 Apr 28;386(17):1668-1669. doi: 10.1056/NEJMc2119768. N Engl J Med. 2022. PMID: 35476655 No abstract available.
-
Nivolumab with or without Relatlimab in Untreated Advanced Melanoma.N Engl J Med. 2022 May 12;386(19):1860. doi: 10.1056/NEJMc2201558. N Engl J Med. 2022. PMID: 35544393 No abstract available.
-
Relatlimab and nivolumab in the treatment of melanoma.Cell. 2022 Dec 22;185(26):4866-4869. doi: 10.1016/j.cell.2022.12.003. Cell. 2022. PMID: 36563660
Similar articles
-
Overall Survival and Response with Nivolumab and Relatlimab in Advanced Melanoma.NEJM Evid. 2023 Apr;2(4):EVIDoa2200239. doi: 10.1056/EVIDoa2200239. Epub 2023 Mar 22. NEJM Evid. 2023. PMID: 38320023 Clinical Trial.
-
First-Line Nivolumab and Relatlimab Plus Chemotherapy for Gastric or Gastroesophageal Junction Adenocarcinoma: The Phase II RELATIVITY-060 Study.J Clin Oncol. 2024 Jun 10;42(17):2080-2093. doi: 10.1200/JCO.23.01636. Epub 2024 May 9. J Clin Oncol. 2024. PMID: 38723227 Free PMC article. Clinical Trial.
-
Nivolumab/Relatlimab: A Novel Addition to Immune Checkpoint Inhibitor Therapy in Unresectable or Metastatic Melanoma.Ann Pharmacother. 2023 Jun;57(6):738-745. doi: 10.1177/10600280221131396. Epub 2022 Oct 21. Ann Pharmacother. 2023. PMID: 36268952 Review.
-
Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma.N Engl J Med. 2022 Feb 3;386(5):449-462. doi: 10.1056/NEJMoa2111380. N Engl J Med. 2022. PMID: 35108470 Clinical Trial.
-
Nivolumab Plus Relatlimab: First Approval.Drugs. 2022 Jun;82(8):925-931. doi: 10.1007/s40265-022-01723-1. Drugs. 2022. PMID: 35543970 Review.
Cited by
-
Current Trends and Innovative Approaches in Cancer Immunotherapy.AAPS PharmSciTech. 2024 Jul 24;25(6):168. doi: 10.1208/s12249-024-02883-x. AAPS PharmSciTech. 2024. PMID: 39044047 Review.
-
Characteristics of tumor microenvironment and novel immunotherapeutic strategies for non-small cell lung cancer.J Natl Cancer Cent. 2022 Oct 20;2(4):243-262. doi: 10.1016/j.jncc.2022.10.002. eCollection 2022 Dec. J Natl Cancer Cent. 2022. PMID: 39036549 Free PMC article. Review.
-
Biomarker development for PD-(L)1 axis inhibition: a consensus view from the SITC Biomarkers Committee.J Immunother Cancer. 2024 Jul 20;12(7):e009427. doi: 10.1136/jitc-2024-009427. J Immunother Cancer. 2024. PMID: 39032943 Free PMC article. Review.
-
T cell dysfunction and therapeutic intervention in cancer.Nat Immunol. 2024 Jul 18. doi: 10.1038/s41590-024-01896-9. Online ahead of print. Nat Immunol. 2024. PMID: 39025962 Review.
-
Multiple Options: How to Choose Therapy in Frontline Metastatic Melanoma.Curr Oncol Rep. 2024 Jun 5. doi: 10.1007/s11912-024-01547-0. Online ahead of print. Curr Oncol Rep. 2024. PMID: 38837107 Review.
References
-
- Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med 2019;381:1535–46. - PubMed
-
- Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. CheckMate 067: 6.5-year outcomes in patients (pts) with advanced melanoma. J Clin Oncol 2021;39:Suppl 15: 9506. abstract.
-
- Workman CJ, Cauley LS, Kim I-J, Blackman MA, Woodland DL, Vignali DAA. Lymphocyte activation gene-3 (CD223) regulates the size of the expanding T cell population following antigen activation in vivo. J Immunol 2004;172:5450–5. - PubMed
-
- Hemon P, Jean-Louis F, Ramgolam K, et al. MHC class II engagement by its ligand LAG-3 (CD223) contributes to melanoma resistance to apoptosis. J Immunol 2011;186:5173–83. - PubMed
Publication types
MeSH terms
Substances
Associated data
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials