Daratumumab Based Response Adapted Therapy for Older Adults With Newly Diagnosed Multiple Myeloma

Inclusion Criteria:

* Understand and voluntarily sign an informed consent form
* Age 65 years or older and presence of coexisting conditions which in the opinion of the treating physician are likely to result in the development of unacceptable side effects associated with high-dose chemotherapy with stem-cell transplantation
* Able to adhere to the study visit schedule and other protocol requirements.
* Diagnosed with multiple myeloma and be considered to have active disease with either elevated Calcium, Renal Failure, Anemia, Bone Lesions (CRAB) criteria (hypercalcemia, renal failure, anemia, or bone lesions) or myeloma defining events (bone marrow ≥ 60% plasma cells, serum free light chain (sFLC) ratio≥ 100 or MRI or Positron Emission Tomography \[PET\] defined lesions). Patients must not have received an active chemotherapy regimen. Patients may have received palliative radiotherapy at least 2 weeks prior to the study start. Dexamethasone up to 160 mg total dose is allowed prior to participation
* Measurable myeloma paraprotein levels in serum (≥ 0.5 g/dL), urine (≥ 0.2 g excreted in a 24-hour urine collection sample) or by serum free light chains (involved free light chain greater than 100mg/L)
* Eastern Cooperative Group (ECOG) Performance Status of 0 - 2.
* Serum bilirubin levels \</=1.5 times the upper limit of the normal range for the laboratory (ULN).
* Serum Aspirtate Transaminase (AST) or serum Alanine Aminotransferase (ALT) levels \</=2 x Upper Limit of Normal (ULN)
* Must have adequate bone marrow function: a. Absolute neutrophil count \> 1,000 cells/mm3 (1.0 x 109/L). b. Platelets \>/= 75,000 /mm3.
* Hemoglobin \> 8 g/dL (transfusions are allowed)
* Calculated creatinine clearance \>/=30ml/min by Cockcroft-Gault formula.
* Men must agree to use a latex condom during sexual contact with a female of child bearing potential even if they have had a successful vasectomy. See Appendix C: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.

Exclusion Criteria:

* Ongoing severe infection requiring intravenous antibiotic treatment.
* Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer from which the subject has been disease-free for at least 2 years.
* Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia.
* Patients with known Chronic Obstructive Pulmonary Disease (COPD) with a forced expiratory volume in 1 second (FEV1) \<50% of predicted normal and , moderate or severe persistent asthma within the past 2 years or uncontrolled asthma. Patients with a history of COPD will have pulmonary function testing to include FEV1
* Uncontrolled medical problems such as diabetes mellitus, congestive heart failure, coronary artery disease, hypertension, unstable angina, arrhythmias), pulmonary, hepatic and renal diseases unless renal insufficiency is felt to be secondary to multiple myeloma.
* Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
* Pregnant or lactating females.
* Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
* Concurrent use of other anti-cancer agents or treatments with the exception for hormonal therapy, which is allowed.
* Known allergy or hypersensitivity or intolerance to any of the study drugs, hyaluronidase, monoclonal antibodies (mAbs), human proteins, or their excipients (refer to daratumumab IB), or known sensitivity to mammalian derived products
* Seropositive for human immunodeficiency virus (HIV)
* Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
* Seropositive for hepatitis C (except in the setting of a Sustained Virologic Response \[SVR\], defined as aviremia at least 12 weeks after completion of antiviral therapy).