Case Report: Immune-Related Toxicity During Adjuvant Treatment With BRAF Plus MEK Inhibitors in a Melanoma Patient

Abstract

Adjuvant treatment of operated melanoma has deeply changed in the last few years with the introduction of immune-checkpoint inhibitors and BRAF/MEK inhibitors. Sarcoidosis is a systemic inflammatory disease causing non-caseous granulomatous reactions. Sarcoid-like granulomatous reactions have been reported in patients with advanced melanoma, mostly related to immunotherapy with immune-checkpoint inhibitors. We report a case of a 38-year-old woman with stage III operated melanoma treated with adjuvant BRAF plus MEK inhibitors, who developed sarcoidosis-like syndrome with systemic involvement, resolved after discontinuation of treatment. The occurrence of immune-related toxicity with the use of MAPK inhibitors supports the hypothesis that this class of drugs may also have an immunological effect, and that the long-term efficacy of adjuvant MAPK inhibitors may be due to their immunological function.

Mediastinal and hilar sarcoid‑like reaction in a patient treated with dabrafenib and trametinib for metastatic melanoma: A case report and review of the literature

“…In any case, such adverse events remain uncommon. We identified 17 documented cases of histologically confirmed granulomatosis under combined treatment with dabrafenib and trametinib in the literature (10,(12)(13)(14)(15)(16)(17)(18)(19)(20), which are summarized in Table I. Men and women seem to be almost equally affected (8/17 vs. 9/17), while patient age varies between 19 and 82 years.…”

“…Men and women seem to be almost equally affected (8/17 vs. 9/17), while patient age varies between 19 and 82 years. All but one patient (16/17) suffered from stage IV melanoma, while in one case granulomatosis was diagnosed during adjuvant treatment for stage III disease (20). Time of treatment until the onset of reactions also varies significantly from 1-20 months.…”

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

“…Sarcoidosis is a multisystem granulomatous disease. This condition is associated with melanoma and can be induced in melanoma patients with anti-PD-1 agents [8][9][10]. It is unclear whether the development of sarcoidosis in these patients represents an autoimmune disease, which was not evident until the onset of melanoma, or rather is a marker of oncologic response.…”

“…Boutros et al [9] reported a case of systemic sarcoidosis with skin involvement during adjuvant treatment with dabrafenib plus trametinib; this patient presented skin and uveal granulomatosis while mediastinal reactive lymph nodes were documented at the thorax CT scan. Moreover, fever and transaminitis were present.…”

Potential immune‑related adverse events during dabrafenib and trametinib treatment: A case series of patients with BRAF V600E melanoma

“…In other two reports (6,7), mediastinal lymphadenopathies coherent with sarcoidosis localization occurred in a metastatic patient receiving dabrafenib and trametinib or vemurafenib and cobimetinib. In another case, a young female treated with adjuvant target therapy received diagnosis of granulomatous synechizing uveitis and cutaneous sarcoidosis located near a tattoo (8).…”