Identification of effective therapy in Langerhans cell histiocytosis in the adult population.

Abstract

7065 Background: Langerhans cell histiocytosis (LCH) is a rare disorder of histiocytic proliferation most commonly observed in children. LCH in adults is less characterized and a standard of care has not been established. Here we review clinical outcomes of adult LCH patients (pts) treated with various therapies at a large referral center. Methods: We identified 108 pts over 18 years of age with histologically confirmed LCH presenting to our center between 1990-2015. Clinical and treatment characteristics were examined and classified by single or multi-system involvement (SSI or MSI, respectively) and risk-organ involvement (ROI; liver, spleen, hematopoietic system and CNS). Overall survival (OS) and freedom from first progression (FFFP) were calculated by the Kaplan-Meier method. Univariate analysis was performed with the Cox proportional hazards model. Results: Median age at diagnosis was 44 years (range 18-89) with a median follow-up of 3.9 years (0.1-9.1). Median OS was 16.1 years and FFFP was 5.6 years, with 94 (87%) pts alive at last follow-up. Eighty-three (77%) had SSI and 13 (12%) had ROI. The most common sites of disease were bone (52 pts; 48%), lung (28; 26%), and skin (24; 22%). Only 11 pts (9%) experienced progression of disease (POD) after first treatment. Twenty-four (22%) received radiotherapy, 42 (39%) underwent excision, and 26 (24%) received systemic therapy at any point during treatment. The most common systemic agents were vinblastine, 6-mercaptopurine (6-MP), methotrexate (MTX), and cladribine. Eight received combination vinblastine, 6-MP, and MTX (VMM), 4 of which had MSI. Median progression-free survival (PFS) of VMM pts was 6 months, compared with 2.8 for all other systemic agents (p = 0.1). For OS, lack of ROI was the only significant variable upon univariate analysis (HR .22, 95%CI 0.06-0.75, p = 0.016). No variables were significant for PFS. Conclusions: Effective therapy for adult LCH has not been clearly identified. In our cohort of both low and high risk patients, the low POD rate observed is encouraging. VMM, a regimen previously studied in pediatric pts, is also effective in adults and may be considered the combination of choice for treatment of adult LCH. Further prospective study is warranted.