A case of refractory IgG4-related disease successfully treated with daratumumab and lenalidomide

Résumé :

Dear Editor, IgG4-related disease (IgG4-RD) is a rare chronic systemic autoimmune disorder. This disease is characterized by severe fibro-inflammation, elevated serum IgG4 concentration, and polytypic tissue infiltrate of lymphocytes and plasma cells enriched with IgG4-positive plasma cells that can lead to organ failure. The diagnosis is based on the classification criteria determined by the ACR and the EULAR [1]. It is commonly accepted that first-line therapy is based on steroids. Although this treatment is efficient in >90% of the cases, the history of the disease is marked by relapses, corticodependence and corticoresistance [2]. Rituximab may be the best option for patients dependent on or refractory to steroids [2, 3]. Because of its recent description, the optimal therapeutic management of IgG4-RD refractory to steroids and rituximab remains unclear. Many studies suggest using immunosuppressive drugs or targeted therapies based on theoretical or retrospective data and several clinical trials are ongoing [4, 5]. Plasma cells and activated lymphocytes of IgG4-RD express CD38, which the daratumumab can target [2]. On the other hand, lenalidomide is an immunomodulatory drug that has direct anti-lymphocyte and plasma cell activity, as well as indirect effects mediated through various immune cells [6]. Moreover, the safety of combining daratumumab, lenalidomide and dexamethasone (D-RD) in MM has been well established [7]. Therefore, we hypothesized that this triplet could be efficient and well-tolerated in targeting IgG4-RD.