Dramatic Response After Switching MEK Inhibitors in a Patient With Refractory Mixed Histiocytosis

Abstract

We report the case of a patient with progressive multisystem mixed histiocytosis associating Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) involving the bone marrow, whose lesions harbored the MAP2K1 E102-I103del. After initial improvement under the MEK inhibitor trametinib, the treatment was only partially efficient and poorly tolerated. Eventually, although the trough blood level of trametinib at steady state was within expected ranges, the disease progressed to a life-threatening situation, with peritoneal involvement and anasarca. Switching to the MEK inhibitor cobimetinib as a salvage therapy resulted in a dramatic, rapid disease response, and the patient remains disease-free 3 years later with the treatment. The load of the MAP2K1 deletion in peripheral blood was correlated with the disease activity and strongly declined with cobimetinib, although it remained detectable at the last follow-up.

Pulmonary Langerhans cell histiocytosis – an update on pathogenesis and treatment

“…However, recently attention has been drawn to the fact that RAF-independent MAP2K1 mutations may be resistant, or only partially sensitive to MEKi [47,48,49 ]. In these situations, ERK inhibitors represent an alternative option.…”