A Case of Pulmonary Sarcoidosis during First-Line Targeted Therapy with Dabrafenib Plus Trametinib in <b><i>BRAF</i></b> V600E-Mutated Metastatic Melanoma

Abstract

BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) exert a cytotoxic and immune-mediated effect on metastatic melanoma. The immune-mediated mechanism can lead to some adverse events, including panniculitis, erythema, keratitis, vitiligo-like lesions, or, more rarely, sarcoid-like skin reactions. In particular, sarcoidosis-related manifestations during melanoma treatment are characterized mainly by skin involvement and are seldom associated with chest or lymph node lesions. Overall, managing these adverse events can be very challenging from the diagnostic and therapeutic points of view. We present a case of pulmonary sarcoidosis; it is the first without skin involvement and initially only with lung presentation, diagnosed during treatment with BRAFi and MEKi for metastatic cutaneous melanoma. After about 2 years of treatment, with an oncological complete response, a histologically confirmed form of pulmonary sarcoidosis was diagnosed and initially interpreted as tumor progression. Sarcoidosis has always remained asymptomatic. After progression in the thorax and supraclavicular lymph nodes, steroid therapy with prednisone was instituted with total remission of the signs of disease. The targeted therapy has never been interrupted, and the patient still shows a complete response. This clinical case suggests that rare immune-mediated events, such as pulmonary sarcoidosis, should be considered during targeted therapy for metastatic melanoma and not only during treatment with immune checkpoint inhibitors. It also suggests that the interruption of targeted treatment should be accurately considered based on the expected risks or benefits since such immune-mediated events may have low clinical impact.

Case Report: Dynamic overlap of melanoma, sarcoidosis, and targeted therapy for BRAF-mutant melanoma

“…We, and others, have reported on sarcoid development for patients receiving anti-neoplastic immunotherapy, and clinicians experienced with immunotherapy commonly see reactive lymphadenopathy during patient management ( 11 , 12 ). There have been reports of sarcoidosis and sarcoid-like reactions to the combination of BRAF and MEK inhibition, described with more frequency in recent years ( 4 , 6 – 10 , 14 ). Given the less intuitive clinical association between sarcoid-like reactions with these targeted therapies, recognition of this potential differential diagnosis is necessary for contemporary melanoma care.…”

“…The primary toxicities of the combination of BRAF and MEK inhibition include drug fever, chills, arthralgia, and diarrhea, which are typically managed by treatment break and dose reduction. Sarcoidosis is a multisystem disease of unknown etiology characterized by the formation of non-caseating granulomas in various organs and has been described both in relation to the presence of melanoma as well as a drug-induced toxicity from anti-melanoma treatments (3)(4)(5)(6)(7)(8)(9)(10)(11)(12).…”