Sarcoidosis in Patients Treated with Vemurafenib for Metastatic Melanoma: A Paradoxical Autoimmune Activation

Abstract

Background: Vemurafenib, a BRAF inhibitor, is a first-line treatment for inoperable melanoma. Sarcoidosis has never been reported in patients on vemurafenib.

Objectives: We describe 5 cases of sarcoidosis in patients treated with vemurafenib.

Methods: Seventy patients receiving vemurafenib for a BRAF-mutated inoperable stage III or IV melanoma were treated in our centre.

Results: Five patients (7.1%) developed sarcoidosis or a sarcoid-like reaction on vemurafenib; 4 patients had cutaneous signs and 3 had extracutaneous disorders (bilateral hilar lymph nodes, uveitis). Histological analysis of skin lesions revealed epithelioid granulomas without necrosis, consistent with sarcoidosis. Angiotensin-converting enzyme levels were high in 2 patients. Cutaneous and ophthalmological lesions rapidly disappeared on topical corticosteroid treatment without the cessation of vemurafenib treatment. Complete remission of melanoma was observed in 3 patients and partial remission was observed in another.

Conclusion: BRAF inhibitors probably have immune system-enhancing effects and should therefore be recognized as potential inducers of sarcoidosis.