MEK Inhibitors Produce Strong, Sustained Responses in Erdheim–Chester Disease

By
Francesco Pegoraro
Félicien Triboulet
Matthias Papo
Francesco Peyronel
Anita Argentieri
Jerome Razanamahery
Ahmed Idbaih
Polyzois Makras
Ofer Shpilberg
Oshrat Hershkovitz-Rokah
Michael Girschikofsky
Matthew Collin
Kristian Bowles
Satyen H. Gohil
Rodothea Amerikanou
Emmanuel Ledoult
Tanguy Le Scornet
Mathilde de Menthon
Etienne Riviere
Xavier Boulu
Henry Dupuy
Achille Aouba
Stanislas Faguer
Xavier Solanich
Elena Sieni
Stéphane Barete
Chiara Bellino
Alessandro Tomelleri
Corrado Campochiaro
Lorenzo Dagna
Zahir Amoura
Jean-François Emile
Fleur Cohen-Aubart
Augusto Vaglio
Julien Haroche
October 6, 2026

Hemasphere

At a Glance

Category	Detail
Condition	Erdheim–Chester disease (ECD), a rare histiocytic cell neoplasm associated with activating somatic mutations in the MAPK pathway.
Key Mechanisms	MAPK-pathway mutations; MEK inhibitors (MEKi) target this pathway.
Target Population	Patients with biopsy-proven ECD or mixed histiocytosis involving ECD who received MEKi monotherapy and had at least 6 months of follow-up.
Care Setting	International, multicenter ECD care centers in eight European countries and Israel; treatment and outcomes were assessed through medical chart review.

Key Highlights

The study screened 206 patients and included 170 patients with ECD treated with MEKi monotherapy.
The cohort was predominantly male (71%); median age at diagnosis was 63 years.
Multisystem disease was reported in 69% of patients, with a median of four involved sites.
Response assessment combined clinical findings with radiologic and metabolic data.
The supplied article excerpt does not include the study's response, toxicity, or survival results.

Guideline-Based Recommendations

Diagnosis

ECD diagnosis followed international consensus guidelines; study eligibility required biopsy-proven ECD or mixed histiocytosis involving ECD.

Management

The study evaluated MEKi monotherapy at any treatment line; it does not provide a treatment recommendation in the supplied excerpt.

Monitoring & Follow-up

Response assessment incorporated clinical findings, MRI or CT, and PET metabolic data.
Adverse events during MEKi monotherapy were evaluated using CTCAE criteria.

Risks

The introduction describes ECD manifestations as heterogeneous and sometimes life-threatening.
Long-term efficacy and tolerability of MAPK inhibitors were identified by the authors as less well established.

Patient & Prescribing Data

170 patients with ECD treated with MEKi monotherapy across eight countries; median age at diagnosis was 63 years, and 71% were male.

Patients received MEKi monotherapy at any treatment line. The supplied excerpt does not report specific regimens, doses, response rates, or adverse-event frequencies.

Clinical Best Practices

Use the international consensus guidelines cited by the study for ECD diagnosis and organ-involvement classification.
Assess response using clinical, radiologic, and metabolic criteria together.
The study defined complete response as complete regression across clinical, radiologic, and metabolic assessments.
Evaluate adverse events during MEKi monotherapy according to CTCAE criteria.