Background Erdheim–Chester disease (ECD) is a non-Langerhans cell histiocytosis characterised by the accumulation of foamy histiocytes in the retroperitoneum, long bones and large vessel areas. In wild-type (WT) BRAF patients, cobimetinib, a MEK inhibitor, has been used with success.
Purpose This study aims to evaluate the efficacy and safety of the MEK inhibitor cobimetinib used in monotherapy for ECD patients without the BRAF mutation.
Material and methods A total of three patients received cobimetinib alone. Through pharmacy software registration and electronic clinical history, we analysed the following variables: age, sex, date of diagnosis, presence of mixed histiocytosis, BRAF status, ECD manifestations, previous treatment and reasons to finish them, date of cobimetinib initiation, cobimetinib dose, initial-final creatinine level, evolution of histiocytic infiltrations and side effects. Cobimetinib efficacy was measured by monitoring histiocytic infiltrations and metabolic response with PET-CT scans. Safety was evaluated by number and severity of side effects.
Results Three patients, who are still on treatment, were included: two men and a woman, with a median age of 50 years. All of them were WT-BRAF and only one patient had mixed histiocytosis. Time from ECD diagnosis until cobimetinib initiation was 11, 22 and 51 months. Manifestations included perirenal infiltration (n=2), long bones hypermetabolism (n=3), retroperitoneal fibrosis (n=2), cardiac involvement (n=1) and arterial affection (n=1). Before cobimetinib monotherapy, they had received pegylated interferon-α and discontinued it because of progression evaluated with PET-CT. All of them received cobimetinib 60 mg/day for 21 days of a 28 day cycle. One patient experienced complete response with three cycles, his creatinine level decreased significantly and he stopped dialysis. Another one reached an excellent metabolic response with three cycles. The third patient experienced stabilisation of perirenal infiltration. Adverse events registered were: rash (n=3), acne (n=2), arthralgia (n=2), diarrhoea (n=3), asthaenia (n=2), cardiac failure (n=1) and erythema (n=1). No patient required dose reduction or stopped the treatment.
Conclusion Cobimetinib represents an option for WT-BRAF patients. However, its toxicity is considerable. Further research is certainly warranted to better define this therapeutic alternative.
Reference and/or acknowledgements Cohen Aubart F, Emile JF, et al. Targeted therapies in 54 patients with Erdheim–Chester disease, including follow-up after interruption (the LOVE study). Blood 2017;130:1377–80.
No conflict of interest.