# Adverse effects of systemic advanced melanoma therapies—do BRAF/MEK inhibitors increase the incidence of mesenteric panniculitis?

## TL;DR

BRAF/MEK inhibitors may increase the risk of mesenteric panniculitis, a condition that can resemble cancer, in melanoma patients.

## Contribution

This study is the first to show a significant association between BRAF/MEK inhibitors and mesenteric panniculitis in melanoma patients.

## Key findings

- BRAF/MEK inhibitor-treated patients had a 7.5% incidence of mesenteric panniculitis compared to 2.9% in ICI-treated patients.
- Mesenteric panniculitis can mimic malignancy, requiring increased clinical awareness in BRAF/MEK inhibitor-treated patients.

## Abstract

BRAF/MEK inhibitors (BRAFi/MEKi) and PD-1 and CTLA-4 immune checkpoint inhibitors (ICI) have revolutionized malignant melanoma treatment and improved patients’ clinical outcome significantly. However, these therapies are associated with substance class-specific side effects. Here, selected cases indicate a correlation between the incidence of mesenteric panniculitis (MP) and BRAFi/MEKi treatment. As MP can mimic or conceal underlying malignancy, the aim of the present study was to confirm a potential correlation with BRAFi/MEKi or ICI in a retrospective, observational analysis of melanoma patients.

In a monocentric retrospective study, abdominal CTs of 490 melanoma patients receiving first-line treatment with ICI (nivolumab, ipilimumab, pembrolizumab, nivolumab/ipilimumab) or BRAFi/MEKi (dabrafenib/trametinib, vemurafenib/cobimetinib, encorafenib/binimetinib) in the adjuvant or advanced situation were evaluated for MP development comparing baseline imaging prior therapy start and follow-up imaging under therapy. MP was defined as an unilocular mesenteric mass characterized by small tissue nodules with increased density of the adjacent fat and a surrounding pseudo-capsule.

384 melanoma patients with ICI (161 women, median age at therapy start: 62 years, IQR: 21 years) and 106 patients with BRAFi/MEKi first-line therapy (46 women, median age: 58 years, IQR: 18 years) were evaluated. MP incidence was significantly higher following BRAFi/MEKi treatment compared to ICI (7.5% vs. 2.9%, p = 0.04). No significance was detected comparing time until MP development from therapy start (174 days, IQR: 518 days [BRAFi/MEKi] vs. 207 days, IQR: 298 days [ICI], p > 0.05).

Our study demonstrates a significant increase in MP development following BRAFi/MEKi treatment compared to ICI in patients with melanoma. As this benign condition can mimic or even conceal malignancy, awareness of its appearance is important.

Question
BRAF/MEK and immune checkpoint inhibitors have revolutionized melanoma treatment but are associated with various side effects, yet data regarding the development of mesenteric panniculitis are scarce.

Findings
BRAF/MEK inhibitor treatment is associated with a significantly higher rate of mesenteric panniculitis compared to immune checkpoint inhibitor treatment in advanced melanoma.

Clinical relevance
BRAF/MEK inhibitor-treated patients are at risk for development of mesenteric panniculitis. As this benign finding can mimic or conceal malignancy, awareness of it is important especially in these patients.