Treatment of Monoclonal Gammopathy-associated C3 Glomerulopathy With Daratumumab-based Therapy

Clinical Practice Points•C3 glomerulopathy represents a heterogeneous group of glomerulonephritides characterized by hyperactivity of the alternative complement pathway.•Although the pathophysiology is incompletely described, there is an increased recognition of the association between this disease and monoclonal gammopathies, especially in older individuals.•Monoclonal gammopathy-associated C3 glomerulopathy responds better to myeloma-directed therapy than traditional immunosuppressive regimens.•The efficacy of daratumumab, a monoclonal antibody directed against CD38 with potent antimyeloma activity, in monoclonal gammopathy-associated C3 glomerulopathy has not been fully characterized in the current literature.•This case report describes the clinical course and outcomes of 2 patients treated with daratumumab-based regimens after an inadequate response to alternative myeloma-directed therapy without daratumumab.•Both patients demonstrated significant hematologic and renal responses after the addition of daratumumab, a finding that warrants further investigation of this agent for monoclonal gammopathy-associated C3 glomerulopathy.