A New Era in pLGG: Expanding the Treatment Toolbox With Targeted Therapy Options

Systemic therapy for pLGG has evolved significantly, offering multiple effective treatment options tailored to the individual needs of each patient. Traditionally, cytotoxic chemotherapy has been the backbone of systemic treatment. Regimens like carboplatin and vincristine or the combination of thioguanine, procarbazine, lomustine, and vincristine have shown success in managing these tumors, particularly when complete surgical resection isn’t possible. Although these therapies are effective, they often require a central line and are associated with immune suppression and other adverse effects.

With growing knowledge of the molecular landscape of these tumors, targeted therapies have emerged as a compelling alternative. Many pLGGs harbor alterations in the MAPK pathway, and the development of oral agents that inhibit this pathway has shifted how clinicians approach treatment. These targeted drugs, such as BRAF or MEK inhibitors, are taken at home and typically don’t require infusion ports. They tend to be better tolerated than traditional chemotherapy, allowing children to maintain more normal daily routines, including attending school and participating in extracurricular activities.

Given that pLGGs are generally indolent but chronic, treatment often spans years and may involve multiple lines of therapy. Clinicians must carefully choose when to use each option from the therapeutic “toolbox,” aiming to balance tumor control with quality of life and long-term outcomes. The goal remains to manage symptoms effectively, slow or stop progression, and help the tumor reach a biologically inactive state later in life. As research continues and more options become available, treatment decisions are increasingly individualized based on tumor biology, patient characteristics, and treatment response.