Current Approaches Among Medical Providers Treating Pediatric Langerhans Cell Histiocytosis

Most pediatric Langerhans cell histiocytosis (LCH) lesions harbor activating mutations within the mitogen-activated protein kinase (MAPK) pathway. MAPK inhibitors (MAPKi) represent a rational therapeutic strategy, though there is no consensus regarding optimal use. We sought to understand how providers currently integrate MAPKi into LCH therapy and gather input regarding potential future clinical trial designs.

An online survey was distributed to members of the Histiocyte Society, Children's Oncology Group, and Asian Histiocytic Disorder Collaborative Group. Domains included demographics, experience treating LCH, preferred treatment in response to clinical vignettes, and opinions regarding clinical trial design.

Participants included 106 pediatric attending physicians from 26 countries. Of the 89 providers with access to MAPKi, 79% have used them to treat LCH, with most reporting use outside of a clinical trial and for recurrent/refractory LCH. Nearly all participants agreed that prospective trials are needed to study MAPKi in newly diagnosed LCH, and 90% felt their institution would open such a trial. Regarding trial design, 89% would include patients with multisystem risk organ (RO) positive disease, while 47% and 21% would include multisystem or single system RO- disease, respectively. Most participants (83%) would include a trial arm combining MAPKi with chemotherapy, with 56% of these participants favoring combination therapy throughout treatment. Additionally, 43% favored including an MAPKi monotherapy arm.

MAPKi are widely available and commonly utilized in pediatric LCH. While treatment practices and trial design preferences vary, there is a strong consensus regarding the need for a prospective clinical trial incorporating MAPKi into upfront therapy.