Abstract
Histiocytic disorders are rare hematologic neoplasms characterized by a notable dependence on mitogen-activated protein kinase signaling. Targeted therapy is an emerging treatment option, yet the number of reported patients remains limited. Here, we describe 40 patients with histiocytic neoplasms who were treated with targeted therapy in 7 tertiary referral hospitals from the Netherlands and Belgium. The cohort comprised of 6 (15%) children and 34 (85%) adults with diverse histiocytoses, including Langerhans cell histiocytosis (LCH; n = 12), Erdheim-Chester disease (n = 14), central nervous system xanthogranuloma (n = 2), Rosai-Dorfman disease (n = 3), histiocytic sarcoma (n = 2), ALK-positive histiocytosis (n = 1), and mixed/unclassifiable histiocytosis (n = 6). Five patients were included in a clinical trial; 35 (88%) received BRAF/MEK inhibitors outside of trials. Among these 35 patients with available follow-up data, median time on targeted treatment was 1.9 years (range, 0.04-5.8 years). Complete or partial responses were observed in 25 of 27 (93%) patients treated for multisystemic and/or solid lesions and 2 of 8 (25%) patients treated for neurodegenerative LCH. Responses were generally durable, although 10 patients lost response after dose reduction or therapy interruption. Responses were recaptured in 9 of 10 cases. Two patients developed new or progressive neurodegenerative lesions: 1 during and 1 after vemurafenib therapy. At last follow-up, 8 adults had stopped targeted therapy because of toxicity. This study corroborates the favorable outcomes of BRAF/MEK inhibition in patients with histiocytosis described previously. However, it also highlights limitations and calls for prospective studies.