Oral Manifestations in Melanoma Patients Treated with Target or Immunomodulatory Therapies

Abstract

BRAF (v-raf murine sarcoma viral oncogene homolog B1) and MEK (mitogen activated protein kinase) inhibitors, as well as immunotherapy against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1), have shown good results in improving the disease-free survival of patients with metastatic melanoma (MM). The aim of this review is to summarize the main oral adverse events (oAEs) occurring in patients undergoing target or immunotherapy. We proposed two separate sections: oAEs during the treatment with (1) target therapies with BRAF and MEK inhibitors and tyrosine kinase inhibitors (gingival hyperplasia, pigmentation disorders, squamo-proliferative lesions) and (2) immunotherapies with CTLA-4 or PD1 inhibitors (lichenoid reactions, immuno-bullous reactions, xerostomia and other reactions). Adverse events frequently include oAEs, although these are often misdiagnosed and under-reported. Indeed, the oral cavity is not routinely evaluated during clinical practice. The symptomatology related to oAEs is significant since it may represent the first manifestation of a severe systemic reaction, possibly leading to difficulties in nutrition with a consequent impact on patients' quality of life. A careful examination of the oral cavity is recommended during the evaluation of oncologic patients in order to promptly detect the onset of new manifestations.

Keywords: adverse event; immunotherapy; melanoma; oral; target.

Figure 1

Oral adverse events and their management occurring during the treatment with target therapies (BRAF inhibitors and tyrosine kinase inhibitors) and immunotherapies (CTLA-4 and PD-1 inhibitors). BRAF (v-raf murine sarcoma viral oncogene homolog B1); CTLA-4 (checkpoints T-lymphocyte-associated protein 4); PD-1 (programmed cell death protein 1).

Figure 2

Clinical presentation of (a) benign gingival hyperplasia in a patient in treatment with a BRAF inhibitor (vemurafenib); (b) a pigmentation of the hard palate induced by imatinib.

Figure 3

Clinical presentation (a) of an oral lichenoid reaction showing reticular features and Wickham’s striae (b,c) in a patient treated with Anti-PD1 (nivolumab).

Figure 4

Oral involvement of a bullous pemphigoid in a patient in immunotherapy with Anti-PD1 (nivolumab).

Figure 5

Steven-Johnson syndrome in patients in treatment with immunotherapy with Anti-PD1 (nivolumab and pembrolizumab) affecting the lips (a,b,c,d) or the tongue (b).

Figure 6

Clinical presentation of a benign migratory glossitis or geographic tongue after the first cycle of nivolumab affecting the dorsal (a) and the lateral (b) surfaces of the tongue.