Efficacy and safety of cladribine in adult pulmonary langerhans cell histiocytosis: a phase II study

Background The efficacy of cladribine in treating pulmonary Langerhans cell histiocytosis (PLCH) has been suggested in select case reports. Treatment-related malignancies remain a concern. Methods In this phase 2 trial, the efficacy and safety of cladribine was evaluated in symptomatic PLCH patients with airflow obstruction and/or a decrease in lung function within the previous year. Cladribine was administered for 4 monthly cycles combined with infectious prophylaxis. Patients were followed up every 3 months during the first year to assess efficacy and then until 48 months. The primary endpoint was the cumulative incidence of response to treatment at 6 months, defined as ≥10% improvement in forced vital capacity (FVC) and/or forced expiratory volume in 1 s (FEV 1 ), with an increase of at least 200 mL in the absolute value of FEV 1 . The study was registered with www.clinicaltrials.gov : NCT01473797 . Results Ten patients (6 men; median age, 37 years; IQR [33; 47.5]; 6 current smokers) were included. The cumulative incidence of response to treatment at 6 months was 70% (CI, 28.4–90.4). The response to cladribine was associated with a median decrease of 14.9 points (IQR [10.5; 23.5]) in the Saint George's Respiratory Questionnaire score. At 12 months, 5 patients were still responders. The duration of infection prophylaxis was 11.8 months [IQR 11.7; 29]. One patient died before the 12-month visit. The remaining patients were alive at 48 months. No, malignancies were detected. Conclusions Cladribine improved lung function in half of the patients at one year of follow-up and was well tolerated overall.