EFFICACY OF INDOMETHACIN AS SALVAGE THERAPY IN CHILDREN AND ADULTS WITH LANGERHANS CELL HISTIOCYTOSIS WITH BONE INVOLVEMENT

Purpose: The aim of this study was to analyze the results of treatment with indomethacin in children and adults with recurrent Langerhans cell histiocytosis (LCH) with bone involvement. Methods: Between 1992 and 2014, 17 patients (median age 37 years, range 1-53) with recurrent LCH and active bone lesions were treated with indomethacin 2 mg/Kg/day (maximum dose 150 mg/day) for a minimum of 3 months. Indomethacin was given alone or in combination with surgery/chemotherapy in 10 (59%) and 7 patients (41%), respectively. BRAF mutation analysis was available in 5 patients. Median follow-up was 24 months. Results: All patients were evaluable for response. Median duration of treatment was 6 month. Fourteen of 17 (82.5%) patients obtained a response, that was complete (CR) in 12 (70.5%) and intermediate (IR) in 2 (17.5%) patients. Concerning the disease status at the time of treatment with indomethacin, a CR was obtained in 4/6 (66.6%), 3/4 (75%) and in 5/7 (71%) patients in first, second and in ≥ 3 recurrences, respectively; an IR was achieved in 1 patient in first and 1 patient in ≥ 3 recurrence. Three patients (1 in first and 2 in ≥ 3 recurrences) had a poor response. Five of 14 responding patients (36%) had a disease recurrence after a median time of 4 months from treatment suspension. Two of 17 patients presented a BRAF mutation; they were treated with indomethacin as a single agent at the third recurrence obtaining a CR, but all of them had a disease recurrence. No side effects were observed. All patients are alive. Conclusions: In our experience indomethacin is effective as salvatage regimen in recurrent LCH, also in patients with multiple recurrences. Prospective studies are needed to identify patients with advanced LCH and bone involvement who can optimally benefit from treatment with indomethacin.