Daratumumab for Polyneuropathy Associated With MGUS

Inclusion Criteria:

1. Age ≥ 18 years at the time of informed consent

2. A diagnosis of chronic demyelinating neuropathy according to the European Federationof Neurological Societies/Peripheral Nerve Society guidelines for chronicinflammatory demyelinating polyneuropathy (as determined by neurologist) withconcurrent diagnosis of monoclonal gammopathy of undetermined significance (MGUS)with an IgM monoclonal peak (see appendix 8)

3. Peripheral neuropathy associated with anti-MAG >7000 BTU, with EMG/NCS consistentwith polyneuropathy.

4. Patients will have to have disability associated with their peripheral neuropathy,with a baseline INCAT Sensory Score (ISS) score ≥4.

5. They must have an ataxia score ≥2 (0 = normal, 1 = slight oscillations, 2 = markedoscillations, 3 = severe ataxia), and/or visual analog pain scale (VAS) >4 (from 0 =no pain to 10 = maximal pain).

6. Must meet MGUS diagnostic criteria as diagnosed using IMWG criteria using thefollowing criteria (see section 1 appendix):

7. Serum monoclonal protein <30g/L

8. Clonal bone marrow lymphoplasmacytic/plasma cells <10%

9. Absence of end-organ damage related to the plasma cell dyscrasia*

10. Serum calcium >0.25 mmol/L (>1mg/dL) higher than the upper limit of normal or >2.75mmol/L (>11mg/dL)

11. Renal insufficiency: creatinine clearance <40 mL per minute or serum creatinine >177mol/L (>2mg/dL)

12. Anemia: hemoglobin value of >20g/L below the lowest limit of normal, or a hemoglobinvalue <100g/L

13. Bone lesions: one or more osteolytic lesion on skeletal radiography, CT, or PET/CT.If bone marrow has <10% clonal plasma cells, more than one bone lesion is requiredto distinguish from solitary plasmacytoma with minimal marrow involvement.

14. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 3 (see appendix)

15. Adequate bone marrow function:

• Total WBC count ≥ 1,500/mm3, ANC ≥ 1,000/mm3

• Hemoglobin (Hb) ≥ 8.0 g/dL,

• Platelet count ≥ 75,000/mm3.

13. Adequate liver function:

• Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 2.5 x upperlimit of normal (ULN)

• Serum aspartate transaminase (AST) or alanine transaminase (ALT) > 2.5 ispermissible if due to disease.

• Bilirubin ≤ 2 x ULN (unless bilirubin rise is due to Gilbert's syndrome or ofnon-hepatic origin for which > 2 x ULN is an acceptable limit)

14. Adequate renal function: creatinine clearance ≥ 20mL/min.

15. Female subjects who are of non-reproductive potential (i.e., post-menopausal byhistory - no menses for ≥1 year; OR history of hysterectomy; OR history of bilateraltubal ligation; OR history of bilateral oophorectomy). Female subjects ofchildbearing potential must have a negative serum pregnancy test upon study entry.

16. Male and female subjects who agree to use highly effective methods of birth control (e.g., condoms, implants, injectables, combined oral contraceptives, someintrauterine devices [IUDs], sexual abstinence, or sterilized partner) during theperiod of therapy and for at least 3 months after the last dose of study drug.

Exclusion Criteria:

1. Documented active multiple myeloma, smoldering myeloma, Waldenstromsmacroglobulinemia, non-IgM MGUS, plasma cell leukemia or systemic amyloid lightchain amyloidosis

2. Concomitant disorder felt to possibly be related to the etiology of the peripheralneuropathy: diabetes, vitamin deficiency, chronic alcohol consumption, drugs, HCVinfection.**

3. Prior or current exposure to any of the following:

4. To daratumumab and Hyaluronidase-fhj or other anti-CD-38 therapies (unless are-treatment study)

5. Exposure to an investigational drug (including investigational vaccine) orinvasive investigational medical device for any indication within 4 weeks or 5pharmacokinetic half-lives, whichever is longer.

6. Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1second (FEV1) < 50% of predicted normal. Note that FEV1 testing is required forparticipants suspected of having COPD and participants must be excluded if FEV1 is < 50% of predicted normal.

7. Moderate or severe persistent asthma within the past 2 years (see Appendix section 1), or uncontrolled asthma of any classification. Note that participants whocurrently have controlled intermittent asthma or controlled mild persistent asthmaare allowed to participate.

8. Participant is:

9. Known history of human immunodeficiency virus (HIV)

10. Seropositive for hepatitis B (defined by a positive test for hepatitis Bsurface antigen [HBsAg]). Subjects with resolved infection (i.e., subjects whoare HBsAg negative with antibodies to total hepatitis B core antigen [anti-HBc]with or without the presence of hepatitis B surface antibody [anti-HBs]) mustbe screed using real-time polymerase chain reaction (PCR) measurement ofhepatitis B virus (HBV) DNA levels. Those who are PCR positive will beexcluded. EXCEPTION: Subjects with serologic findings suggestive of HBVvaccination (anti-HBs positivity as the only serologic marker) AND a knownhistory of HBV vaccination, do not need to be testing for HBV DNA by PCR.

11. Seropositive for hepatitis C (except in the setting of a sustained virologicresponse [SVR], defined as a viremia at least 12 weeks after completion ofantiviral therapy).

12. Patients who have implanted deep brain stimulators and vagal nerve stimulators.

13. Clinically significant cardiac disease, including:

14. Myocardial infarction within 6 months before randomization, or unstable oruncontrolled disease/condition related to or affection cardiac function (e.g.,unstable angina, congestive heart failure, New York Heart Association ClassIII-IV) [refer to Appendix section 3]

15. Uncontrolled cardiac arrhythmia

16. Patients with external pacing wires or intracardiac catheters

17. If patient is unable to sign informed consent due to any serious medical condition,laboratory abnormality or psychiatric illness

18. If patient is pregnant or breastfeeding, a prisoner, or not yet an adult

19. Any life-threatening illness, medical condition, concomitant active cancer, or organsystem dysfunction that, in the investigator's opinion, could compromise thesubject's safety or put the study outcomes at undue risk.