INDOMETHACIN AS FIRST LINE TREATMENT OF LANGERHANS CELL HISTIOCYTOSIS (LCH). A 20-YEAR EXPERIENCE OF A SINGLE CENTRE.

Purpose: The aim of this study was to analyse the results of treatment with indomethacin as first line treatment in children and adults with Langerhans cell histiocytosis (LCH). Methods: Between 1999 and 2018, 47 patients with a diagnosis of LCH (CD1a+, S100+, CD207+) with a median age of 29 years (range 1-66) were treated with indomethacin 2 mg/Kg/day (maximum dose 150 mg/day) as first line (21 in combination with surgery and/or chemotherapy). Twentyseven patients (57.5%) had single system diseases (SS-LCH), 20 unifocal (74%) and 7 multifocal, and 20 (42.5%) presented multi-system involvement (MS-LCH). BRAF mutation analysis was available in 8/47 patients. Results: Thirty-eight of the 47 patients (81%) were evaluable for response. Two patients (4%) discontinued indomethacin due to toxicity. Considering patients evaluable for response, the median treatment duration was 3 months. All patients obtained a response, that was complete (CR) in 23 (60%) and intermediate (IR) in 15 (40%). Considering the disease status, 16/24 (66.6%) SS-LCH and 7/14 (50%)MS-LCH patients achieved a CR, while an IR was recorded in 8/24 (33.4%) SSLCH and in 7/14 (50%) MS-LCH patients. The CR rate was higher in patients treated with indomethacin as a single agent regimen (14/2, 66.6%) than in those who received a combination regimen (9/17, 53%). Disease reactivation occurred in 2/38 (5%) patients after 3 and 17 months, respectively, from treatment suspension. Three of 8 tested patients (37.5%) were BRAF mutated; all of them obtained a durable CR without recurrence. The most common toxicity was hypertension, recorded in 5/38 (13%) patients. All patients are alive. Conclusion: Our experience shows that indomethacin, used as single agent or in combination, is an effective first-line treatment, for SS-LCH and MS-LCH with bone involvement.