Notes on 'Relative Change in S100 as a Biomarker of Survival in Patients With Metastatic Melanoma Treated With Pembrolizumab'

Study Overview

Objective: Evaluate the relationship between relative changes in S100 protein levels at 12 weeks of immunotherapy and survival in patients with metastatic melanoma treated with pembrolizumab.
Background: Baseline S100 levels have been shown to have prognostic value, but their role during/after therapy in survival is unclear.
Key Finding: A relative change in S100 levels >145% at 12 weeks is associated with significantly shorter progression-free survival (PFS) and overall survival (OS).

Melanoma is a skin cancer with increasing incidence over the last four decades.
Immunotherapies, such as PD1 and CTLA4 inhibitors, are changing treatment paradigms.
Pembrolizumab is a PD1 inhibitor that prevents tumor tolerance and aids in destroying cancer cells.
Despite improvements, 60% of patients don't respond to PD1 monotherapy.

S100 is expressed in glial cells and melanocytes, linked to brain tumors, and melanoma.
High S100 is associated with metastatic disease and shorter survival.
Previous studies suggest S100 early changes during immunotherapy predict disease response.
This study aims to further explore S100 as a biomarker by focusing on relative changes post-therapy.

Study Design: Retrospective analysis at Clinical Hospital Centre Zagreb.
Patients: 38 patients with metastatic melanoma treated with pembrolizumab.
Treatment Protocol: Pembrolizumab at 2 mg/kg every 3 weeks.
Outcome Measures:
- OS: Time from start of immunotherapy to death or loss of contact.
- PFS: Time from start of immunotherapy to clinical or radiological progression, or death.
Data Analysis:
- S100 levels before and 12 weeks after treatment initiation.
- Statistical analyses: Mann-Whitney U-tests, chi-squared tests, Kaplan-Meier method, Cox proportional hazard model.

Patient Demographics: Predominantly male, average age 63.4 years, majority with 3+ metastatic sites.
Survival Analysis:
- Average OS: 22.4 months; PFS: 15.6 months.
- No correlation between baseline S100 and OS.
- Significant correlation between 12-week S100 levels and survival.
- S100 >145% results in shorter PFS (5.1 vs. 18.5 months) and OS (5.7 vs. 26.3 months).
- Multivariate analysis confirms S100 >145% as a significant predictor of poor survival (HR=32.25).

Immunotherapy has improved melanoma outcomes, but assessing efficacy remains complex.
Study highlights importance of relative S100 changes as a biomarker compared to baseline levels.
Challenges remain in identifying the optimal cut-off for S100 changes.
Relative S100 change >145% shows potential as an early indicator of therapy response, possibly guiding treatment modifications.

Single-center study with a small sample size.
Retrospective nature limits conclusions to associations only.
Possible selection bias due to including only patients with at least two S100 evaluations.

A relative change in S100 is a promising biomarker for predicting survival in metastatic melanoma under immunotherapy.
Further research is needed to refine S100 change thresholds and understand their implications.

The study includes references to previous research validating S100’s role and recent findings regarding immunotherapy.

Study Contributors: LS and MG led the analysis; KB, KM, and DH contributed to data collection and analysis. Conflict of Interest: None disclosed.

Received: February 17, 2020. Revision received: February 28, 2020. Accepted: March 4, 2020.