BRAF, MEK inhibitors ‘saving lives’ as histiocytic disorder treatment

Key takeaways:

  • Most patients treated with BRAF and MEK inhibitors for histiocytic disorders showed no active disease.
  • Langerhans cell histiocytosis is a rare disorder affecting 1 in 200,000 children.

NEW ORLEANS — BRAF and MEK inhibitors may show promise as a treatment option for children and adults with histiocytic disorders, according to a presenter here.

Langerhans cell histiocytosis (LCH), categorized under histiocytic neoplasms, is a rare pediatric disease affected one in every 200,000 children, Ashish Kumar, MD, PhD, of Cincinnati Children’s Hospital Medical Center, said during his presentation at The Society for Pediatric Dermatology Meeting, which preceded the American Academy of Dermatology Annual Meeting. Manifestations of the disease include asymptomatic bone lesions and multi-organ disease.

Baby in Swing

 BRAF and MEK inhibitors may show promise as a treatment option for children and adults with histiocytic disorders. Image: Adobe Stock.

Currently, the standard treatment for LCH is chemotherapy; however, failure rates tend to reach approximately 45%.

“We have new treatments that are more effective than the standard of therapy,” Kumar told Healio. “These new treatments are not just more effective — they are saving lives and saving the patients from suffering.”

LCH is most driven by activated mutations in the mitogen-activated protein (MAP)-kinase pathway and has been shown to respond well to BRAF and MEK inhibitors, including dabrafenib and trametinib.

According to the presentation, researchers collected data in using off-label dabrafenib and trametinib as first-line therapy in 34 patients with histiocytic disorders, primarily LCH. A total of 12 patients were treated with dabrafenib, 20 patients with trametinib and two patients with both.

Of the 16 relapsed patients, seven showed no active disease, five showed no active disease but had residual organ damage, and three showed improvement in signs and symptoms. One patient with the rare multisystem histiocytosis Rosai-Dorfman disease did show disease progression while on therapy, which Kumar attributed to the patient not having any identifiable mutations in the MAP-kinase pathway.

Of the 18 newly diagnosed patients, all patients showed no active disease after treatment, although five had residual diabetes insipidus.

These results may provide treatment options that are “easier than chemotherapy” for patients suffering from histiocytic disorders.

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