Short Course Daratumumab in Patients With Multiple Myeloma

Inclusion Criteria:

- Multiple Myeloma according to the International Myeloma Working Group definition (2)
i.e.:Clonal bone marrow plasma cells ≥ 10% or biopsy-proven bony or extramedullary
plasmacytoma and any one or more of the following myeloma defining events and/or one
or more of the biomarkers for malignancy at the time of diagnosis:

- Myeloma defining events:

- Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit
of normal or >2.75 mmol/L (>11 mg/dL)

- Renal insufficiency: creatinine clearance <40 mL per min or serum creatinine >177
µmol/L (>2 mg/dL)

- Anemia: hemoglobin value of >20 g/L below the lower limit of normal, or a
hemoglobin value <100 g/L

- Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or
PET-CT

- Biomarkers of malignancy:

- Clonal bone marrow plasma cell percentage ≥60%

- Involved: uninvolved serum free light chain ratio≥100

- >1 focal lesions on MRI studies

- A very good partial response (VGPR) or better after induction therapy with/without
consolidative chemotherapy and/or HDT/ASCT.

- Very good partial response (VGPR):

- Serum and urine M-component detectable by immunofixation but not on
electrophoresis or

- ≥90% or greater reduction in serum M-component plus urine M-component <100 mg per
24 h

- Complete response (CR):

- Negative immunofixation of serum and urine and

- Disappearance of any soft tissue plasmacytomas and

- <5% plasma cells in bone marrow

- Stringent complete response (sCR)

- CR as defined above plus

- Normal free light chain ratio and

- Absence of clonal cells in bone marrow by immunohistochemistry or
immunofluorescence

- MRD positive by flow cytometry

- Additionally, patients who were previously MRD negative for >/= 3 months after
induction therapy with/without consideration HDT/ASCT and have turned MRD positive (by
flow cytometry) within the last 3 months and do not have any evidence of progressive
disease are eligible.

- Patients must be on standard of care lenalidomide maintenance therapy for at least 6
months at the time of study enrollment

- Patient can be receiving bisphosphonate therapy per the treating oncologist's
discretion

- Creatinine clearance ≥45 ml/min using the Cockcroft-Gault method, MDRD, or CKD-EPI
formula. If the calculated CrCl based on Cockcroft-Gault method, MDRD, or CKD-EPI is
<45 mL/min, patient will have a 24 hr urine collection to measure CrCl.

- Age ≥18 years

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Male or female patient who accepts and is able to use recognized effective
contraception (oral contraceptives, IUCD, barrier method of contraception in
conjunction with spermicidal jelly) throughout the study when relevant.

- Absolute neutrophil count (ANC) ≥1.0 x 10^9/L, hemoglobin ≥8 g/dL, and platelet count
≥75 x 10^9/L. No transfusion or growth factor support for one week prior to labs.

- Adequate hepatic function, with bilirubin < 1.5 x the ULN, and AST and ALT < 2.5 x ULN

Exclusion Criteria:

- Patients with a diagnosis of MM not achieving a VGPR or better to the most recent
therapy.

- Patients with a diagnosis of MM who are MRD Negative by flow cytometry

- Patients must not have measurable disease at the time of enrollment. Measurable
disease is defined as follows

- Serum monoclonal protein > 0.5 gm/dL

- Urine monoclonal protein > 200 mg/24 hours

- Involved serum free light chain > 10 mg/dL

- Pregnant or lactating females

- Uncontrolled hypertension or diabetes

- Active hepatitis B or C infection

- Has significant cardiovascular disease with NYHA Class III or IV symptoms, or
hypertrophic cardiomegaly, or restrictive cardiomegaly, or myocardial infarction
within 3 months prior to enrollment, or unstable angina, or unstable arrhythmia

- Uncontrolled intercurrent illness including but not limited to active infection or
psychiatric illness/social situations that would compromise compliance of study
requirements

- Active infection requiring treatment within two weeks prior to first dose

- Contraindication to any concomitant medication, including antivirals, anticoagulation
prophylaxis, tumor lysis prophylaxis, or hydration given prior to therapy

- Major surgery within 1 month prior to enrollment

- Previous therapy with daratumumab or other anti-CD38 monoclonal antibodies

- History of other malignancy (apart from basal cell carcinoma of the skin, or in situ
cervix carcinoma) except if the patient has been free of symptoms and without active
therapy during at least 5 years

- Active infection requiring treatment within two weeks prior to first dose