RESUMEN
BACKGROUND: Treatment with BRAF inhibitors (BRAFI) and MEK inhibitors (MEKI) causes cutaneous reactions in children, limiting dosing or resulting in treatment cessation. The spectrum and severity of these reactions is not defined. OBJECTIVE: To determine the frequency and spectrum of cutaneous reactions in children receiving BRAFI and MEKI and their effects on continued therapy. METHODS: A multicenter, retrospective study was conducted at 11 clinical sites in the United States and Canada enrolling 99 children treated with BRAFI and/or MEKI for any indication from January 1, 2012, to January 1, 2018. RESULTS: All children in this study had a cutaneous reaction; most had multiple, with a mean per patient of 3.5 reactions on BRAFI, 3.7 on MEKI, and 3.4 on combination BRAFI/MEKI. Three patients discontinued treatment because of a cutaneous reaction. Treatment was altered in 27% of patients on BRAFI, 39.5% on MEKI, and 33% on combination therapy. The cutaneous reactions most likely to alter treatment were dermatitis, panniculitis, and keratosis pilaris-like reactions for BRAFI and dermatitis, acneiform eruptions, and paronychia for MEKI. CONCLUSIONS: Cutaneous reactions are common in children receiving BRAFI and MEKI, and many result in alterations or interruptions in oncologic therapy. Implementing preventative strategies at the start of therapy may minimize cutaneous reactions.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Erupciones por Medicamentos/epidemiología , Neoplasias/tratamiento farmacológico , Paroniquia/epidemiología , Inhibidores de Proteínas Quinasas/efectos adversos , Adolescente , Canadá/epidemiología , Niño , Preescolar , Erupciones por Medicamentos/diagnóstico , Erupciones por Medicamentos/etiología , Femenino , Humanos , Lactante , Masculino , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Paroniquia/inducido químicamente , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Estudios Retrospectivos , Estados Unidos/epidemiologíaRESUMEN
Nivolumab is an immune checkpoint inhibitor acting on programmed cell death protein 1 (PD-1) that has been used to treat a growing number of malignancies. Cutaneous side effects are common with nivolumab treatment, though they are typically self-limited. Here we present a case of persistent lichenoid dermatitis in a patient treated with nivolumab for renal cell cancer. The patient then developed Stevens-Johnson syndrome 9 months after initiation of nivolumab, with no other identifiable offending medication in the interim. Although an unusual presentation, a growing number of cases have reported delayed Stevens-Johnson syndrome/toxic epidermolytic necrosis-like reactions to immune checkpoint inhibitors. Awareness of this phenomenon is imperative for prompt recognition and treatment of potentially life-threatening cutaneous side effects.