Novel and Personalized Therapy for Monoclonal Gammopathy of Renal Significance

Monoclonal gammopathy of renal significance (MGRS) refers to renal diseases caused by a monoclonal protein (M protein) secreted by a small plasma cell clone or other B-cell clones in patients who do not meet the diagnostic criteria for multiple myeloma or other B-cell malignancies. MGRS results from the deposition of composite monoclonal immunoglobulin (Ig) and light or heavy chain (LC or HC) fragments of varying sizes produced by plasma cells or plasmoblasts that proliferate clonally, possibly under the influence of T-helper lymphocytes. The diagnosis of MGRS involves four steps: (1) identifying the underlying monoclonal protein in serum and urine, (2) determining the clonal B-cell population responsible for secreting the monoclonal protein, (3) assessing any extrarenal manifestations of the clonal B-cell population, and (4) performing a renal biopsy to identify the pattern of renal parenchymal damage and detect monoclonal protein. Treatment for MGRS is based on targeting the causative B-cell clone. The goal of treatment is to preserve or improve organ function by targeting the B-cell or plasma cell clone responsible for M-protein production and organ damage. Several substances are available for treatment, including proven options such as bortezomib, cyclophosphamide, and pomalidomide, as well as newly developed substances like CD38 antibodies (daratumumab, isatuximab), monoclonal antibodies targeting BCMA, BCL-2 inhibitors (venetoclax), and chimeric antigen receptor (CAR) T-cells.