Novel Combination Therapy With Lenalidomide and Trametinib for Treatment-Resistant Xanthoma Disseminatum With...

Xanthoma Disseminatum (XD) is a rare histiocytic myeloid neoplasm involving the skin, mucosa, and sometimes the pituitary gland, and shares histologic features with juvenile xanthogranuloma (JXG). Given its rarity, there are no standardized treatment guidelines for XD, and management decisions are largely based on case reports and clinical judgment. We present the case of a patient with XD who had extensive, disfiguring cutaneous lesions and disabling synovial involvement of the hips and knees with secondary bone erosions. The patient was initially treated with three separate lines of therapy, cladribine, cobimetinib, and clofarabine, all of which were discontinued due to either a lack of rapid clinical response or significant toxicity. Due to both a lack of rapid response and toxicities, his therapeutic regimen was changed to reduced-dose trametinib along with lenalidomide. This combination led to a marked clinical and radiographic improvement across all affected sites. To our knowledge, this represents the first reported case of successful treatment of XD using a combination of a MEK inhibitor and lenalidomide.