PA03 Trametinib therapy for congenital melanocytic naevi

Abstract We reviewed our departmental experience of all children treated with trametinib for melanocytic lesions. Eleven patients were identified from the period 2010–2025 and hospital notes were reviewed. Four patients had congenital melanocytic naevi (CMN) with leptomeningeal melanoma, two had CMN with leptomeningeal melanocytic dysplasia, four had benign but hyperproliferative multinodular cutaneous CMN and one had leptomeningeal melanoma without cutaneous involvement. All patients with leptomeningeal disease had an NRAS driver; all other patients had a BRAF fusion. The average age at initiation of trametinib was 3.6 years (range 0.7–12.2) and the mean duration was 1.2 years (range 0.2–5.7). Four of five patients with leptomeningeal melanoma had an objective and clinically relevant improvement in neurological symptoms and signs, but subsequently died at a mean age of 2.9 years, after a mean of 0.4 years of therapy (range 0.2–0.8); the fifth is alive after 0.7 years with no progression. One patient with leptomeningeal dysplasia has had radiological evidence of improvement and attenuation of neurological symptoms and continues on trametinib after 5.7 years; however, the other had limited objective response and discontinued after 3 years. All patients with the hyperproliferative cutaneous phenotype have had objective sustained response, with reduction in nodular bulk and pruritus, and incidental lightening of naevus and hair. Trametinib was overall well tolerated, with no retinal problems or cardiomyopathy. However, three patients had paronychia, one had recurrent herpes simplex lesions within the CMN, and four had transient abnormalities in creatinine or creatine kinase. Dermatitis was frequent, but resolved with dose reduction without loss of efficacy in benign hyperproliferative disease. Trametinib is useful in NRAS-driven leptomeningeal melanoma in children, but not sufficient to prevent relapse, and can be helpful in NRAS-driven leptomeningeal dysplasia. It is very helpful symptomatically in BRAF fusion-driven cutaneous disease, where a reduced dose after initial response appears to sustain efficacy and reduce adverse effects.