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Objectives <p>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.</p> Materials and methods <p>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.</p> Results <p>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%, <i>p</i> = 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], <i>p</i> &gt; 0.05).</p> Conclusion <p>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.</p> Key Points <p><Emphasis Type="BoldItalic">Question</Emphasis> <i>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</i>.</p> <p><Emphasis Type="BoldItalic">Findings</Emphasis> <i>BRAF/MEK inhibitor treatment is associated with a significantly higher rate of mesenteric panniculitis compared to immune checkpoint inhibitor treatment in advanced melanoma</i>.</p> <p><Emphasis Type="BoldItalic">Clinical relevance</Emphasis> <i>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</i>.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月1日

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  • Marcel Alexander Drews,
  • Alexander Baumgarten,
  • Sebastian Zensen,
  • Marcel Opitz,
  • Denise Bos,
  • Lisa Zimmer,
  • Selma Ugurel,
  • Johannes Haubold,
  • Dirk Schadendorf,
  • Elisabeth Livingstone,
  • Benedikt M. Schaarschmidt

摘要

Objectives

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.

Materials and methods

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.

Results

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).

Conclusion

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.

Key Points

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.

Graphical Abstract