# Primary Tumor Characteristics as Biomarkers of Immunotherapy Response in Advanced Melanoma: A Retrospective Cohort Study

## TL;DR

This study finds that patients with cutaneous melanoma respond better to immunotherapy than those with acral or unknown primary melanoma.

## Contribution

The study identifies cutaneous melanoma subtypes as significant predictors of immunotherapy response and survival in advanced melanoma patients.

## Key findings

- Cutaneous melanoma subtypes are associated with better progression-free and overall survival.
- Acral and unknown primary melanomas show inferior response to immunotherapy.
- Metastatic stage and BRAFV600E mutation are linked to worse outcomes.

## Abstract

Melanoma survival rates have been vastly improved by the use of immune checkpoint inhibitors. However, some patients do not respond to the treatment or experience progression of disease. Because of this variability of response, markers predicting efficacy of these treatments is of interest. This study aimed to clarify the role of primary tumor characteristics in melanoma treatment and survival. The authors demonstrated that cutaneous melanoma and its subtypes were significantly associated with response, progression-free survival, and overall survival compared with acral or unknown primary melanoma. Other primary features did not demonstrate an association on multivariable analyses. Thus, primary features, other than cutaneous primary, should likely not influence metastatic treatment selection.

Identifying patients likely to benefit from immune checkpoint inhibitor (ICI) treatment remains a crucial goal for melanoma. The objective of this study is to assess the association between primary tumor features and immunotherapy response and survival in advanced melanoma patients. In this single-center retrospective cohort study, disease characteristics, response to immunotherapy, PFS, and OS were assessed among melanoma patients (excluding mucosal and uveal primaries) treated with ICI. Among 447 patients, 300 (67.1%) received anti-PD-1 monotherapy and 147 (32.9%) received ipilimumab/nivolumab. A total of 338 (75.6%) had cutaneous melanoma, 29 (6.5%) had acral melanoma, and 80 (17.9%) had melanoma of unknown primary. Ulceration and stage at initial presentation were associated with inferior outcomes on univariate analysis. However, on multivariate analysis, this result was not observed, but cutaneous melanoma and each of its subtypes (superficial spreading, nodular, other, unknown) were positively associated with response, longer PFS, and longer OS. Metastatic stage (M1c, M1d) at presentation (OR = 1.8, p < 0.05) and BRAFV600E mutation status (OR = 1.6, p < 0.001) were associated with shorter PFS. This study is limited by its retrospective and single-center design. Cutaneous melanoma and its subtypes were significantly associated with response, PFS, and OS compared with acral or unknown primary melanoma.