LGG-30. TRAMETINIB-ASSOCIATED HYPONATREMIA IN A CHILD WITH LOW GRADE GLIOMA IS NOT SEEN FOLLOWING TREATMENT WITH ALTERNATIVE MEK INHIBITOR

Abstract

Molecularly targeted therapy with MEK inhibitors is increasingly being incorporated into the treatment of pediatric low-grade gliomas (LGGs). Trametinib is an orally available MEK1/2 inhibitor that has demonstrated tumor control in LGGs with BRAF alterations. Safe expansion of MEK inhibitor therapy within the pediatric patient population demands adequate understanding of and surveillance for potential MEK-inhibitor specific toxicities, especially among young children. Hyponatremia has been reported in adult patients receiving BRAF/MEK inhibitor combination treatment as well as in two pediatric patients with known diabetes insipidus treated with trametinib monotherapy. To our knowledge, single-agent trametinib has not previously been reported to be associated with hyponatremia in children in the absence of an underlying endocrinopathy. We present a case of hyponatremia associated with trametinib use in an infant with progressive LGG without known endocrine dysfunction, which recurred after significant dose reduction. Therapy with an alternative MEK1/2 inhibitor, binimetinib, provided excellent tumor response without hyponatremia. Hyponatremia is a rare but serious side effect of trametinib, even without underlying pituitary dysfunction. Infants and patients lacking the ability to quickly regulate fluid intake in response to osmolality changes are at particular risk of suffering severe consequences from hyponatremia and should be monitored closely with initiation of trametinib. Switching to a different drug within the same class may offer an alternative to significant dose reduction or discontinuation due to this toxicity.