Effects of Daratumumab Monotherapy on Bone Parameters in Patients With Relapsed and /or Refractory Multiple Myeloma

Inclusion Criteria:

1. Males and females at least 18 years of age.

2. Voluntary written informed consent.

3. Subject must have documented relapsed or refractory multiple myeloma as defined by thecriteria below: a. Measurable disease as defined by any of the following:

• Serum monoclonal paraprotein (M-protein) level ≥ 1.0 g/dL (except for IgAsubtype: ≥ 0.5 g/dL) or urine M-protein level ≥ 200 mg/24 hours; or

• Light chain multiple myeloma for subjects without measurable disease in the serumor urine by SPEP/UPEP: Serum immunoglobulin free light chain ≥ 10 mg/dL andabnormal serum immunoglobulin kappa lambda free-light-chain ratio.

4. Prior treatment with at least two lines of therapy including lenalidomide and a PI forMM (induction followed by any planned high dose therapy or consolidation ormaintenance would be considered as one regimen).

5. Documented evidence of progressive disease as defined by the IMWG 2014 on or after thelast regimen.

6. Karnofsky Performance Status score of ≥ 70.

7. All of the following laboratory test results during screening:

• Absolute neutrophil count (ANC) of ≥1.0 x 109/L.

• Platelet count of ≥ 75 x 109/L in patients in whom <50% of bone marrow nucleatedcells are plasma cells and ≥50 x 109/L in patients in whom more than 50% of bonemarrow nucleated cells are plasma cells.

• Hemoglobin value (> 7.5 g/dL).

• Alanine aminotransferase level ≤2.5 times the upper limit of normal (ULN).

8. Adequate renal function (CrCl ≥ 30 mL/min by CKD-EPI).

9. Willingness and ability to participate in study procedures.

10. Reproductive Status:

11. Women of childbearing potential (WOCBP) must have two negative serum or urinepregnancy tests, one 10-14 days prior to start of the study drug and one within 24 hours prior to the start of study drug.

12. Women must not be breastfeeding.

13. WOCBP must agree to follow instructions for effective methods of contraceptionfor 4 weeks before the start of treatment with study drugs, for the duration oftreatment with study drugs, and for 3 months after cessation of study treatment. Male patients must use a latex or synthetic condom during any sexual contact with femalesof reproductive potential, even if they have undergone a successful vasectomy. They mustalso agree to follow instructions for methods of contraception for 4 weeks before the startof treatment with study drugs, for the duration of treatment with study drugs, and for atotal of 3 months post-treatment completion.

Exclusion Criteria:

1. Patient has received any of the following therapies:

• Radiotherapy or systemic therapy within 2 weeks of baseline.

• Prior Allogeneic hematopoietic stem cell transplantation within 12 weeks ofbaseline.

• Prior Treatment with any CD38-antibody (i.e. isatuximab).

2. Clinically significant cardiac disease, including:

3. Myocardial infarction within 6 months, or unstable or uncontrolled condition (e.g., unstable angina, congestive heart failure, New York Heart AssociationClass III-IV).

4. Cardiac arrhythmia (CTCAE Grade 3 or higher) or clinically significant ECGabnormalities.

5. ECG showing a baseline QT interval as corrected >470 msec.

6. Chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1second (FEV1) <50% of predicted normal. Note that FEV1 testing is required forsubjects suspected of having COPD and subjects must be excluded if FEV1 <50% ofpredicted normal.

7. Known active hepatitis A, B, or C.

8. Known HIV infection.

9. Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior toenrolment.

10. Hypersensitivity to the active substance or to any of the excipients.

11. Any concurrent medical or psychiatric condition or disease (e.g., active systemicinfection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) thatis likely to interfere with subject's ability to give informed consent, the studyprocedures or results, or that in the opinion of the investigator, would constitute ahazard for participating in this study.

12. Pregnant or breastfeeding women.