38P - Biomarkers predictive of response to immune checkpoint inhibitor therapy in patients with metastatic melanoma

Background

Immune Checkpoint Inhibitors (ICIs) have substantially improved the prognosis of metastatic melanoma. However, not all patients benefit equally. To optimize patient selection for ICIs and minimize immune-related toxicity in those with a low likelihood of response, it is essential to identify predictive biomarkers. Our study assessed the association between certain patient characteristics and response to ICIs, progression-free survival (PFS), and overall survival (OS).

Methods

In this retrospective, observational study, we included 49 patients with metastatic melanoma treated with Pembrolizumab or with Nivolumab + Ipilimumab. Collected parameters included sex, age, BRAF V600E mutation status, localization of metastases, baseline lactate dehydrogenase (LDH) and neutrophil to lymphocyte ratio (NLR), best overall response (bOR) achieved, development and type of immune related adverse events (irAEs), dates of progression and death. All statistical analyses were performed using Jamovi, version 2.5.4.

Results

Most patients (57.1%) received Nivolumab + Ipilimumab, with an Overall Response Rate (ORR) of 35.7%, while ORR for Pembrolizumab was 28.5%. For the entire cohort, median PFS and OS were 9.1 months and 21 months, respectively. We found a significant association between the response to ICIs and irAEs, with a relative risk (RR) of 2.93 (p= 0.01). Cutaneous irAEs, including vitiligo, occurred in 52.4% of patients and were associated with a higher RR of 3.45 (p = 0.003). There was no association between response to ICIs and LDH, NLR, sex, age or BRAF status. Patients with elevated LDH (>245 U/L) had significantly shorter OS than those with normal LDH, with HR: 3.26 (95% CI: 1.16-9.17), p < 0.05. Similarly, patients with elevated NLR (cut-off values: 3.46 for PFS, 4.13 for OS) had significantly shorter PFS and OS than those with low NLR (p < 0.05), with corresponding hazard ratios of 1.23 (95% CI: 1.03-1.47) for PFS and 1.34 (95% CI: 1.09-1.64) for OS.

Conclusions

The development of irAEs, particularly cutaneous irAEs, may serve as an indicator of response to ICIs in metastatic melanoma patients. Baseline LDH and NLR levels have prognostic significance, but are not predictive of response to ICIs.

Editorial acknowledgement

During the preparation of this work the author(s) used ChatGPT in order to rephrase sentences, make them shorter/ more concise in order to better express the meaning and fit inside the character limit. After using this tool/service, the author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.