Anakinra improves retention rate of targeted treatments in Erdheim-Chester disease

Objective: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis that exhibits a wide spectrum of clinical manifestations. The recent identification of activating mutations in the MAPK-ERK pathway in patients with ECD has led to the introduction of targeted therapies. The most commonly used targeted therapies are BRAF- and MEK-inhibitors, which are highly effective but also carry significant toxicity. The aim of our study was to assess drug retention of targeted therapies in ECD patients from two Italian referral centers and to investigate the influence of a combined anakinra plus targeted therapy approach. Methods: We retrospectively analyzed drug retention rate in a cohort of ECD patients who received targeted therapies, alone or combined with anakinra. Results: Among 52 patients undergoing 60 treatment courses, vemurafenib (72%) was the most used drug, followed by cobimetinib (23%), trametinib (3%), and dabrafenib (2%). The overall 18-month drug retention rate (DRR) for all the treatment courses was 72%, with no significant differences between agents. Adverse reactions were the leading cause (76%) of discontinuation. Sixteen patients (27%) received a combined treatment with anakinra. This combination therapy was associated with a significantly higher 18-month DRR (94% vs 65%, p = 0.0251). Survival analysis also showed that drug retention was better in the anakinra group (log-rank test p = 0.040). Conclusions: ECD patients on targeted therapies showed an overall 18-month DRR of 72%, with no significant differences between specific molecules. The combination of anakinra and targeted therapies was associated with a significantly improved drug retention.