Background Langerhans cell histiocytosis (LCH) involves abnormal
proliferation of Langerhans cells (LC), which is typically driven by the
BRAF V600E mutation. High-risk LCH has a poor prognosis. Procedure
Fifteen children (5 girls, 10 boys) with BRAF V600E+ LCH received
vemurafenib (initial dose median 40 mg/kg/day, range: 11–51.6
mg/kg/day) between March 2016 and February 2020. All patients had
previous received LCH-directed chemotherapy. The median age at LCH onset
was 2 months (range: 1–28 months) and the median age at the start of
vemurafenib treatment was 22 months (range: 13–62 months). The median
disease activity score (DAS) at the start of vemurafenib treatment was
12 points (range: 2–22 points). Results The median duration of
vemurafenib therapy was 29 months (range: 2.4–45 months). All patients
responded to treatment, with median DAS values of 4 points (range: 0–14
points) at week 4 and 1 point (range: 0–3 points) at week 26.
Toxicities included skin/hair changes (93%) and non-significant QT
prolongation (73%). Two patients died, including 1 patient who
experienced hepatic failure after NSAID overdose and 1 patient who
developed neutropenic sepsis. Electively stopping vemurafenib treatment
resulted in relapse in 5 patients, and complete cessation was only
possible for 1 patient. Digital droplet PCR for BRAF V600E using
cell-free circulating DNA revealed that 7 patients had mutation statuses
that fluctuated over time. Conclusion Our study confirms that
vemurafenib treatment is safe and effective for young children with BRAF
V600E+ multisystem LCH. However, treatment using vemurafenib does not
completely eliminate the disease.
Langerhans Cell Sarcoma Arising from Small Lymphocytic Lymphoma: Lineage Analysis and BRAF V600E Mutation study
