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 II 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 end-point 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 ≥200 mL in the absolute value of FEV 1 . The study was registered with ClinicalTrials.gov ( NCT01473797 ). Results 10 patients (six men; median (interquartile range (IQR)) age 37 (33–47.5) years; six current smokers) were included. The cumulative incidence of response to treatment at 6 months was 70% (95% CI 28.4–90.4%). The response to cladribine was associated with a median (IQR) decrease of 14.9 (10.5–23.5) points in the St George's Respiratory Questionnaire Total score. At 12 months, five patients were still responders. The median (IQR) duration of infection prophylaxis was 11.8 (11.7–29) months. 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 1 year of follow-up and was well tolerated overall.