Nivolumab/Relatlimab: A Novel Addition to Immune Checkpoint Inhibitor Therapy in Unresectable or Metastatic Melanoma

Abstract

Objective: The aim of this article is to assess available data regarding use of nivolumab/relatlimab for adult and pediatric patients 12 years of age and older with unresectable or metastatic melanoma. Data Sources: A search of PubMed conducted from August 2019 to August 2022 with the search terms Opdualag, nivolumab AND relatlimab, and BMS-986016 resulted in 14 publications. Study Selection and Data Extraction: Relevant clinical trials written in English language were analyzed. Data Synthesis: Nivolumab/relatlimab was approved by the Food and Drug Administration following results of a phase 1/2 trial and phase 2/3 RELATIVITY-047 trial. Nivolumab/relatlimab demonstrated a median progression free survival (PFS) of 10.1 months in the first-line setting without new safety signals. The PFS benefits appear greatest in those with programmed cell death-ligand 1 (PD-L1) <1% and lymphocyte activation gene-3 (LAG-3) ≥1%. Adverse effects commonly experienced were immune related in nature and require early identification and prompt management. Grade 3 or 4 adverse effects occurred in 18.9% of patients. Relevance to Patient Care and Clinical Practice: For patients 12 years of age and older with unresectable or metastatic melanoma, nivolumab/relatlimab offers a new first-line treatment option. Evaluation of PD-L1 expression along with concomitant use of medications with potential interactions should be evaluated when deciding if nivolumab/relatlimab is the most appropriate treatment option. Conclusions: Nivolumab/relatlimab adds an additional first-line treatment option demonstrating promising improved PFS for patients with unresectable or metastatic melanoma, particularly those with PD-L1 <1% and/or LAG 3 ≥1%. Additional uses of nivolumab/relatlimab may be on the horizon as further clinical trials are ongoing.

Immunologic Signatures of Peripheral Blood T Cells Reveal the Outcome of p53MVA Vaccine and Pembrolizumab Treatment in Patients with Advanced Ovarian Cancer

“…Merck's LAG-3–targeting antibody favezelimab has already been tested in combination with pembrolizumab in a first-in-human study in advanced colorectal cancer with promising antitumor activity ( 46 ). In addition, a fixed-dose combination of the LAG-3 blocking antibody relatlimab and the PD-1 blocking antibody nivolumab, known as opdualag (Bristol Myers Squibb) approved by the FDA, has shown a promising improvement in PFS for patients with unresectable or metastatic melanoma ( 47 ).…”

Tissue biomarkers of immune checkpoint inhibitor therapy

“…62 Bristol Myers Squibb's drug, Opdualag, the first fixeddose combination treatment of nivolumab and relatlimab, has recently received Food and Drug Administration approval for the first-line treatment of unresectable or advanced melanoma. 63 This coblockade of LAG-3 and PD-1 has demonstrated both safety and efficacy, offering superior benefits in terms of PFS compared with PD-1 blockade alone. 63 A phase II and III double-blind, randomized trial reported that combining the two ICs, LAG-3 and PD-1, demonstrated a more significant advantage in terms of 1-year PFS (47.7% vs. 36.0%) in comparison to anti-PD-1 monotherapy in patients with untreated metastatic or unresectable melanoma.…”

“…63 This coblockade of LAG-3 and PD-1 has demonstrated both safety and efficacy, offering superior benefits in terms of PFS compared with PD-1 blockade alone. 63 A phase II and III double-blind, randomized trial reported that combining the two ICs, LAG-3 and PD-1, demonstrated a more significant advantage in terms of 1-year PFS (47.7% vs. 36.0%) in comparison to anti-PD-1 monotherapy in patients with untreated metastatic or unresectable melanoma. 64 Importantly, in the group receiving relatlimab-nivolumab, 18.9% of patients experienced treatment-related adverse events (grade 3 or 4), while for the nivolumab group, this percentage was lower (9.7%).…”

“…≥10 mutations/megabase) 62 . Bristol Myers Squibb's drug, Opdualag, the first fixed‐dose combination treatment of nivolumab and relatlimab, has recently received Food and Drug Administration approval for the first‐line treatment of unresectable or advanced melanoma 63 . This coblockade of LAG‐3 and PD‐1 has demonstrated both safety and efficacy, offering superior benefits in terms of PFS compared with PD‐1 blockade alone 63 .…”

Nivolumab/Relatlimab-rmbw: A Novel Dual Combination Therapy to Treat Adult and Pediatric Patients With Unresectable or Metastatic Melanoma

“…13 The expression of LAG-3 may be observed on the cellular membrane of several immune cells, such as CD4 + , CD8 + , natural killer cells, and regulatory T cells. 14,15 LAG-3 cell surface receptor is induced on effector T lymphocytes in response to antigenic stimulation and its expression is maintained at high levels on CD4 + and CD8 + T lymphocytes in response to persistent antigen stimulation, being upregulated in melanoma. 4,16 The classic ligands of LAG-3 are major histocompatibility complex class II molecules, which are abundantly expressed in cutaneous melanomas.…”