HDCN Abstract:  ASN Annual Meeting 2020 -- Digital Meeting  

Fenoglio R, Sciascia S, Roccatello D, et al.

Treatment of AL Amyloidosis with Daratumumab Monotherapy

ASN Annual Meeting 2020 -- Digital Meeting
J Am Soc Nephrol (Oct) 31:10A 2020

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.

c Copyright 2020 -2021 American Society of Nephrology. Reproduced with permission.
All ASN abstracts from the 2020 Annual Meeting are available at this link and also are archived in .pdf form at ASN-Online.org

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