Soluble IL-2 receptor levels support diagnosis of sarcoidosis-like reaction in melanoma patients on immunotherapy - a diagnostic algorithm based on a single center retrospective study.

Background and objectives: Drug-induced sarcoidosis-like reaction (DISR) is an adverse event with emerging importance during immune checkpoint inhibitor (ICI) treatment in melanoma patients. Its reported frequency varies widely, making accurate diagnosis crucial. Distinguishing DISR from tumor progression is challenging, and misdiagnosis may lead to detrimental treatment changes. Thus, reliable diagnostic markers complementing histopathology as well as a diagnostic algorithm are needed.

Patients and methods: This single-center retrospective study, conducted at the University Medical Center in Leipzig, Germany, from 09/2019 to 06/2021, assessed DISR prevalence in melanoma patients treated with ICI for metastatic melanoma. We examined clinical characteristics, radiology, histopathology, and serum parameters.

Results: From a total of 177 patients 19 patients were suspicious for DISR. Of those, DISR was diagnosed in seven patients. In a further nine patients DISR was highly probable based on radiological findings and noticeably increased soluble interleukin-2-receptor (sIL2R) levels, resulting in DISR prevalence of 9%. No patient required permanent discontinuation of ICI due to DISR.

Conclusions: In melanoma patients receiving ICI, DISR is common. Histological confirmation through mediastinoscopy or pulmonary wedge resection offers the highest diagnostic accuracy. When histology is not available, sIL2R levels can aid diagnosis. We propose an algorithm to distinguish DISR from tumor progression.