Association of NRAS mutations and tertiary lymphoid structure formation with clinical outcomes of adjuvant PD-1 inhibitors for acral melanoma.

Abstract

OBJECTIVES:

This study evaluates the efficacy of programmed death-1 (PD-1) inhibitors as adjuvant therapy for acral melanoma (AM) and the predictive value of genetic mutations and tertiary lymphoid structures (TLSs).

METHODS AND RESULTS:

A single-center retrospective longitudinal cohort study was conducted between October 1, 2018, and September 31, 2022. Patients with stages II-III completely resected AM were treated with at least two doses of adjuvant PD-1 inhibitors. A total of 44 participants were included in the final analysis, of which 41 patients with stage III. The median follow-up time, median relapse-free survival (RFS), and median distance metastasis-free survival (DMFS) for all patients were 18.4 months, 21.6 months, and 30.6 months, respectively. 21 (47.7%) and 20 (45.5%) patients were intravenously administered pembrolizumab and toripalimab, respectively. There were no significant differences in RFS (24.4 months vs. 18.9 months, p = 0.432) or DMFS (30.6 months vs. not reached, p = 0.865) between the pembrolizumab and toripalimab groups, respectively. The median DMFS (41.1 months vs. 9.0 months, p < 0.001) in the wild-type NRAS group was significantly longer than that in the NRAS mutation group. Overall, different levels of TLSs infiltration did not significantly affect patient survival. Only three people discontinued treatment due to adverse events. No treatment-related death occurred during the study period.

CONCLUSION:

Our study suggests that adjuvant toripalimab and pembrolizumab therapy have comparable efficacies in patients with AM and are both well tolerated. Adjuvant monotherapy with PD-1 inhibitors may not be appropriate for AM with NRAS mutations.

• Authors: Zeming Mo, Jie Liu, Jinyan Zhang, Yaotiao Deng, Miao Xu, Yu Jiang
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 124 Issue Pt B Pg. 110973 (Nov 2023) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 37769536 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• Immune Checkpoint Inhibitors
• Adjuvants, Immunologic
• NRAS protein, human
• Membrane Proteins
• GTP Phosphohydrolases

Topics

• Humans
• Immune Checkpoint Inhibitors (therapeutic use)
• Retrospective Studies
• Longitudinal Studies
• Tertiary Lymphoid Structures (drug therapy)
• Melanoma (drug therapy, genetics)
• Skin Neoplasms (drug therapy, genetics)
• Adjuvants, Immunologic (therapeutic use)
• Recurrence
• Mutation
• Membrane Proteins (genetics)
• GTP Phosphohydrolases (genetics)