Treatment of Patients with Monoclonal Gammopathy of Clinical Significance

Moreno, David F.; Rosiñol, Laura; Cibeira, María Teresa; Bladé, Joan; Fernández de Larrea, Carlos

SIMPLE SUMMARY: Monoclonal gammopathy of clinical significance (MGCS) is a recently recognized clinical-pathological entity. Symptoms are caused by the presence of a monoclonal protein leading to high comorbidity. The affected organs vary according to the target antigen However, as most of the knowledge relies on case reports or short series; there is a lack of consensus regarding treatment approach. Here, we discuss MGCS other than renal (skin, ocular, neurologic, and bleeding disorders). We provide insights into the pathophysiology, diagnosis, treatment, and follow-up based on clinical cases. Finally, we discuss future directions in this field, such as potential novel therapeutic targets and prognosis of patients with MGCS. ABSTRACT: Monoclonal gammopathy of undetermined significance (MGUS) is defined as the presence of a monoclonal protein (M-protein) produced by a small amount of plasma cells. The majority of patients remain asymptomatic; however, a fraction of them develop clinical manifestations related to the monoclonal gammopathy despite not fulfilling criteria of multiple myeloma or other lymphoproliferative disorder. These patients constitute an emerging clinical issue coined as monoclonal gammopathy of clinical significance (MGCS). The mechanisms involved are poorly understood, and literature is scarce regarding management. The clinical spectrum involves symptoms related to renal, neurologic, skin, ocular, or bleeding manifestations, requiring a multidisciplinary approach. Treatment strategies rely on the basis of symptomatic disease and the M-protein isotype. In this review, we focus on MGCS other than renal, as the latter was earliest recognized and better known. We review the literature and discuss management from diagnosis to treatment based on illustrative cases from daily practice.