Thromboembolic toxicity observed with concurrent trametinib and lenalidomide therapy

Abstract

The event-free survival of pediatric low-grade gliomas is poor, and patients often require multiple treatment strategies. While MEK and RAF inhibitors are efficacious in early-phase trials, not all patients respond, and many experience progression following completion of therapy. Evaluating combination therapies that may enhance efficacy or prolong disease stabilization is warranted. We report our institutional experience using concurrent trametinib and lenalidomide in the treatment of primary pediatric central and peripheral nervous system tumors. Two of four patients using this combination therapy experienced severe thromboembolic events, necessitating discontinuation of therapy. This combination requires further investigation, and we urge caution if used.

Toxicity in combined therapies for tumours treatments: a lesson from BAG3 in the TME?

“…As well, combining ICIs with DNA damage repair inhibitors (DDRIs) in the treatment of urologic cancers greatly increases the risk of toxicity and side effects ( 2 ). In pediatric patients affected by primary CNS or PNS tumours, MEK inhibitor (MEKI) (trametinib)- induced cardiotoxicity combined with the prothrombotic properties of an immunomodulatory agent (lenalidomide) was observed to lead to significant thromboembolic events, requiring termination of this combination regimen ( 3 ). In patients affected by endometrial cancer, the combined use of a tyrosine kinase inhibitor (TKI), lenvatinib, and the ICI pembrolizumab raised concern for the long-term toxicity management ( 4 ).…”