MEK inhibitors show 70% response rate in international Erdheim–Chester disease cohort

An international observational study assessed real-world outcomes of MEK inhibitor monotherapy in 170 patients with Erdheim–Chester disease, a rare histiocytic neoplasm with limited evidence guiding targeted therapy. Investigators across eight countries evaluated response dynamics and predictors, treatment retention, and safety; 159 patients (94%) were evaluable for response.

Objective responses occurred in 112 evaluable patients (70%), disease stabilization in 35 (22%), and progression in 12 (8%). Median time to best response was 14 months, and the estimated two-year probability of response was 61% (95% CI 51%–67%). Response rates were independent of treatment line and underlying molecular alterations. In multivariable analysis, dyslipidemia and neurodegeneration were associated with lower response probability, whereas cutaneous and gastrointestinal involvement were associated with higher probability.

After a median follow-up of 27 months, treatment retention was 76%, with most discontinuations attributed to toxicity. Adverse events occurred in 106 patients (62%) and were severe in 39 (23%). Estimated two-year event-free survival was 65% (95% CI 57%–72%), and overall survival was 80% (95% CI 72%–86%).

These findings support MEK inhibition as an active treatment option in ECD, while highlighting substantial toxicity and potentially prolonged time to best response. The observational design limits causal interpretation. Only the abstract was available, restricting assessment of response definitions, individual regimens, and potential confounding.