The goal of this clinical trial is to learn if drug daratumumab works to treat kidney diseases other than AL-amyloidosis that fall under the category of monoclonal gammopathy of renal significance (MGRS).

The main questions it aims to answer are:

Does daratumumab have an effect on the patients' renal function or the amount of proteinuria?

Does daratumumab have an effect on the hematological endpoints evaluated by minimal residual disease (MRD) and the difference between involved and uninvolved free light chain (dFLC)?

Also changes in quality of life (according to EORTC QLQ-C30) and mechanism of complement system activation are evaluated. The number of patiets with partial or very good partial hematological remission and the number of patients with adverse events related to daratumumab are also recorded.

Inclusion Criteria:

1. Males or females ≥ 18 years of age

2. Subject has provided informed consent prior to initiation of the study or subject's legally acceptable representative has provided informed consent prior to the study when the subject has any kind of condition that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent.

3. Renal biopsy confirmed MGRS-disease

   • Renal biopsy must not be older than 3 months before informed consent. However, if renal biopsy is older than 3 mo and the study team is convinced that major histological changes have not occurred, a biopsy older than that can exceptionally be accepted.
   • Renal transplant patients are allowed

4. Amount of proteinuria ≥ 500 mg/24 h OR eGFR ≥ 20 ml/min prior to the study

5. Previous anticlonal treatment is allowed if deemed ineffective

Exclusion Criteria:

1. Myeloma or systemic AL amyloidosis (smoldering myeloma sized plasma cell clone is allowed when in association with a documented MGRS condition and AHL amyloidosis and AH amyloidosis are included)

2. Cancer that requires treatment,

3. MGRS related to B-cell malignant disorders,

4. Known HIV infection, active hepatitis C infection (subjects with hepatitis C that achieve a sustained virologic response after antiviral therapy are allowed), or hepatitis B infection (subjects with hepatitis B surface antigen or core antibody that achieve sustained virologic response (PCR negativity in HBVNh) with antiviral therapy are permitted with a requirement for regular monitoring for reactivation for the duration of treatment on the study),

5. Pregnancy or breastfeeding,

6. Cyclophosphamide within 6 months of enrollment, or oral high-dose prednisone or equivalent within 6 weeks of enrollment;

   • prednisone or its equivalent at a dosage of ≤10 mg daily for a condition unrelated to MGRS (e.g. asthma or gout) allowed.
   • mycophenolate mofetil (MMF), calcineurin inhibitors (CNI) or azathioprine treated patients are eligible if proteinuria is not improving or if kidney function is declining despite treatment with these medications. Once therapy with daratumumab started, these medications need to be discontinued unless they are used as immunosuppressive medication due to renal transplantation.

7. In patients who previously received rituximab, reconstitution of B cells (CD19 normalized, Ly-B-CD19 lab.code 8329) required.

8. Inability to use daratumumab and to comply with the study protocol as assessed by treating nephrologist and/or hematologist (e.g. severe psychiatric illness, severe lung disease, known allergy to daratumumab)