Abstract: TH-PO647

Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits in Adolescent Patient Successfully Treated with Daratumumab

Session Information

Category: Nephrology Education

  • 1302 Fellows and Residents Case Reports

Authors

  • Drosou, Maria Eleni, Mayo Clinic, Rochester, Minnesota, United States
  • Salameh, Hassan A., Mayo Clinic, Rochester, Minnesota, United States
  • Fervenza, Fernando C., Mayo Clinic, Rochester, Minnesota, United States
  • Leung, Nelson, Mayo Clinic, Rochester, Minnesota, United States
Background

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a renal complication of monoclonal gammopathy of renal significance (MGRS). Treatment with renin-angiotensin system blockade and immunosuppressive therapy with steroids, cyclosporine, cyclophosphamide, mycophenolate mofetil, and clone directed with rituximab and bortezomib have produced varying results. Daratumumab is a monoclonal antibody that targets the CD38 antigen on the surface of plasma cells. Since 50% of the clones in PGNMID are plasma cell in origin, this makes daratumumab a reasonable treatment option.

Methods

A 17 year old previously healthy female patient presented with nephrotic syndrome and hematuria without renal function impairment. Laboratory findings included serum albumin of 2.4 g/dl, serum creatinine (Scr) of 0.8mg/dl and proteinuria of 9 g/d. Renal biopsy revealed a PGNMID with IgG3 lambda deposits. Serum and urine monoclonal studies were negative and serum free light chains were normal.

Results

Initial treatment included steroids, mycophenolic acid and rituximab transiently reduced proteinuria to below the nephrotic range. In the next 7 months, multiple doses of intravenous steroids was administered for recurrent proteinuria and hematuria.Twelve months after initial presentation, proteinuria was back up to 5 g/d and bortezomib dexamethasone was started. Proteinuria initially improved to 2 g/d but was increasing to 3 g/d. The decision was made to add daratumumab to bortezomib dexamethasone. After 2 cycles, proteinuria was reduced by 80% to 0.7 g/d and the hematuria resolved. Scr was stable at 0.8 mg/dl.

Conclusion

To our knowledge, this is the first case of PGNMID treated with daratumumab. The young age of this patient made the treatment options more limited as preservation of her future fertility was a concern and little data exist on the long term effects of immunomodulatory drugs (IMiDs) on teratogenicity of future pregnancy. Daratumumab was chosen in order to avoid some of these complications. In combination with bortezomib and dexamethasone, it was very effective at reducing proteinuria and resolving her hematuria. With its high activity against plasma cells and its safety profile, daratumumab could be an excellent choice in the treatment of MGRS patients.