Melanocytic lesion evolution patterns with targeted therapies and immunotherapies for advanced metastatic melanoma

Background/Objectives: Various cutaneous side effects have been reported with anti-melanoma systemic therapies, including pigmentary changes in melanocytic lesions. We aim to investigate the pigmentary changes in melanocytic lesions amongst patients on four different systemic anti-melanoma therapies.
Methods: We analysed all serial dermatoscopic photographs of melanocytic lesions from patients with metastatic melanoma on either BRAF-inhibitor monotherapy, dabrafenib combined with trametinib (CombiDT), anti-programmed cell death protein 1 (anti-PD1), or anti-PD1 combined with ipilimumab seen from February 2013-May 2016. These were compared to a group of control patients with a personal history of melanoma.
Results: In the control group, 19.0% of lesions lightened, 64.3% didn't change and 16.7% darkened. Only the BRAF-inhibitors group showed more darkening than the controls (37.1% vs 16.7% darkened, p<0.001). More lightening were observed in the CombiDT therapy group (86.2% vs 19.0%, p<0.001) and anti-PD1 and ipilimumab (58.5% vs 19.0%, p<0.001) than controls. Patients on anti-PD1 monotherapy had more lightening (48.9%) and less darkenings (8.9%) than the controls, but the differences were insignificant. Seven lesions with structural changes were excised, and 3 were lentigo maligna.
Conclusions: We showed that different anti-melanoma therapies have different effects on melanocytic lesion pigmentation. BRAFi caused darkening, while CombiDT and anti-PD1 caused lightening compared to controls. The findings emphasise the importance of regular dermatological monitoring for patients on anti-melanoma systemic therapy. Clinicians should expect changes in the global pigmentation of melanocytic lesions, but be suspicious of lesions with structural changes.

Dr. Cathy Zhao