Clinical benefit with tebentafusp in a patient with GNAQ mutant metastatic blue nevus-associated melanoma

Abstract

Melanoma arising in association with a blue nevus (BN) is rare but has molecular similarities to uveal melanoma (UM), including GNAQ/11 mutations. Tebentafusp was recently approved for UM based on improved overall survival in a phase 3 study. We hypothesized that tebentafusp may be active in BN-associated melanoma. Here, we present a case of metastatic BN-associated melanoma with rapid response and ~1 year of disease control on tebentafusp. We also explore molecular and histological features of secondary resistance. Our case highlights that PD-1-resistant melanomas should be screened for GNAQ/11 mutations, as tebentafusp may be a treatment option in this extremely rare disease.

Keywords: Bispecific T cell engager - BiTE; Immunotherapy; Melanoma.

Figure 1. Disease and treatment course. (A) Timeline and (B) CT scan with intravenous contrast prior to and during tebentafusp treatment with months denoting time pre-tebentafusp and post-tebentafusp for (B). CVD, cisplatin, vinblastine, dacarbazine; EBRT, external beam radiation therapy; ECOG, Eastern Cooperative Oncology Group Scale; POD, progression of disease; RT, radiation therapy.

Figure 2. Molecular exploration of tebentafusp resistance. (A) Broad copy number alterations based on MSK impact. Loss or gain is relative to estimated ploidy (liver lesion is diploid while renal lesion is whole genome doubled). (B) Venn diagram of mutations and associated (C) gene list from whole exome sequencing. ZNF736 contained two mutations, one unique to the renal lesion, the other shared. (D) H&E stain and immunohistochemistry for Gp-100 (HMB45) and HLA class I (clone A4) of renal escape lesion versus pre-tebentafusp scalp primary. No on-treatment tissue was available for analysis. (E) Blood lymphocyte depletion immediately following tebentafusp.