Background
Melanoma in-transit metastases (ITMs) are a challenge to treat and associated with systemic disease and poor prognosis. Topical diphencyprone (DPCP), a potent contact sensitizer, is an established treatment for melanoma ITMs. This exploratory study investigated the utility of
BRAF
mutation status, CD8, PD-1, PD-L1, and TILs distribution as biomarkers for response of ITMs to topical immunotherapy (DPCP).
Methods
The ITM deposits of 40 patients treated with DPCP were subjected to biomarker analysis for
BRAF
status, CD8 and PD-1 expression on tumor-infiltrating lymphocytes (TILs), and tumor PD-L1 expression. Response to DPCP and overall survival (OS) were compared by biomarker status.
Results
After 12 weeks, 10 patients (25%) had a complete response, 12 patients (30%) had a partial response, and 18 patients (45%) had no response. No significant association was found between any individual biomarker and response to DPCP or OS. The
BRAF
mutation rate was 25% (10/40). All the patients with a complete response had
BRAF
wild-type tumor. Peritumoral CD8+ T-cells were associated with complete response (
P
= 0.041). Both CD8+ and PD-1 expressions were highly correlated (
P
< 0.0001), and the highest levels of PD-1 expression were detected at the peritumoral interface (
P
= 0.0004). Only two cases were PD-L1-positive, and both had a complete response to DPCP (
P
= 0.043).
Conclusion
Patients who have
BRAF
wild-type tumor are more likely to experience a complete response to DPCP. Peritumoral TILs and PD-1 expressions may predict a better response to DPCP. Expression of PD-L1 may be associated with a complete response to DPCP. A larger prospective study is required.