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Kidney Week

Abstract: TH-OR33

Treatment of AL Amyloidosis with Daratumumab Monotherapy

Session Information

Category: Onco-Nephrology

  • 1500 Onco-Nephrology

Authors

  • Fenoglio, Roberta, 1Nephrology and Dialysis Unit & CMID (Center of Research of Immunopathology and Rare Diseases), Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hub Hospital of Turin, and Department of Clinical and Biological Sciences, University of Turin, Turin, Italy, Turin, Italy, Italy
  • Sciascia, Savino, 1Nephrology and Dialysis Unit & CMID (Center of Research of Immunopathology and Rare Diseases), Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hub Hospital of Turin, and Department of Clinical and Biological Sciences, University of Turin, Turin, Italy, Turin, Italy, Italy
  • Roccatello, Dario, 1Nephrology and Dialysis Unit & CMID (Center of Research of Immunopathology and Rare Diseases), Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hub Hospital of Turin, and Department of Clinical and Biological Sciences, University of Turin, Turin, Italy, Turin, Italy, Italy
Background

Immunoglobulin light chain amyloidosis (AL) is characterized by poor outcome. Daratumumab (D) is a first in class anti CD38 human antibody (IgG1κ) which proved to be effective in combination with bortezomib in MM refractory to conventional bortezomib-based regimens. Its effectiveness and safety in the treatment of AL amyloidosis is under study. This study reports the experience with D monotherapy in a series of severe patients (pts) with AL amyloidosis and multiorgan and biopsy-proven renal involvement.

Methods

Five pts, mean age 64 years were treated with D following antibody testing and extended RBC antigen phenotyping. Treatment protocol was as follows: 16 mg/kg D i.v. administered weekly for 8 weeks, then every 2 weeks (8 doses), and then monthly for 1 year.

Results

In pt #1, in dialysis, who was refractory to conventional therapies D administration resulted in normalization of the FLC ratio with disappearance of serum M-component and Bence-Jones (BJ) proteinuria. In pt #2 who had a relapsing disease, D treatment resulted in a rapid decrease of proteinuria and N-terminal propeptide (NT-pro-BNP) levels with disappearance of serum M-component and BJ proteinuria and normalization of the FLC ratio. Pt #3 was treated front-line. He had an impressive decrease of proteinuria and NT-proBNP levels with normalization of FLC ratio and disappearance of serum M-component. In pt #4, who was intolerant to conventional regimens, D therapy resulted in decrease in proteinuria, disappearance of serum M-component and improvement in the FLC ratio, which were paralleled by a reduction of NT-proBNP levels. Pt #5 had a relapsing disease. D achieved a decrease of proteinuria, a decrease of serum M-component with increase of FLC ratio. This was the only patient who experienced an infusion reaction during the first dose. The 4 pt with still preserved renal function also showed renal response with sCr improvement or stabilization and a decrease in proteinuria levels These data were paralleled by the reduction of NT-proBNP values in the 3 pts with cardiac involvement.

Conclusion

Daratumumab monotherapy resulted in the disappearance of M-proteins in every pt with FLC ratio normalization in 4 out of 5 subjects and impressive decrease of proteinuria and pro-BNP values proving to be an effective therapeutic option for pretreated/naïve patients with severe AL with renal involvement.