CTNI-20. ADDRESSING SKIN ADVERSE EVENTS (AES) DURING MIRDAMETINIB TREATMENT IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 1-ASSOCIATED PLEXIFORM NEUROFIBROMAS (NF1-PN): GUIDANCE FROM A MULTIDISCIPLINARY GROUP OF EXPERTS ON THE MANAGEMENT OF MEK INHIBITOR-A

Abstract ReNeu (NCT03962543) is a trial of the investigational, oral, selective MEK1/2 inhibitor (MEKi) mirdametinib in adults (≥18 years) and children (2-17 years) with NF1-PN. Skin adverse events (AEs) were common in ReNeu, and some discontinuations were noted with low-grade AEs. A multidisciplinary team retrospectively reviewed skincare practices at one high-enrolling site (n=12) with no discontinuations due to skin AEs; these were incorporated into ReNeu trial recommendations and recently updated. The purpose was to prevent/manage skin AEs and maintain protocol treatment adherence. MEKi skin AEs vary by pubertal status, therefore recommendations also vary by pubertal status. All patients were counseled to adopt hygienic skincare practices, including bathing daily, and using mild cleansers and hypoallergenic skin moisturizers (cream or ointment-based emollient; minimum BID) to prevent dry skin. Prepubescent patients were advised to incorporate diluted bleach baths (3-4 times/week) when initiating mirdametinib or after rash development. Treatments recommended for mild-to-severe dermatitis were hydrocortisone cream (2.5% BID) on face/skinfold areas and triamcinolone ointment (0.1% BID) on trunk/extremities. Treatments for mild acneiform eruptions included topical clindamycin lotion (1.0% BID) until resolution, with optional hydrocortisone cream (2.5% BID). For moderate-to-severe acneiform eruptions, cephalexin (20 mg/kg/day divided BID, max 500 mg, ≤6 weeks), amoxicillin (25 mg/kg/day divided BID, max 875 mg, ≤6 weeks), or oral fluconazole (20 mg/kg/day, max 100 mg, 5 days then once weekly for 3 months) were suggested. Postpubescent patients were advised to initiate topical 1.0% clindamycin lotion and oral doxycycline or minocycline (50-mg daily, 3 months) with mirdametinib initiation. Patients with subsequent mild-to-severe acneiform eruptions were advised to apply hydrocortisone cream (2.5% BID) or triamcinolone ointment (0.1% BID). Referral to a dermatologist was suggested for all patients with uncontrolled dermatitis, worsening acneiform eruptions, or infection. Proactive skincare practices appeared effective at this site, but prospective validation is necessary before making clinical recommendations.