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

This is a Phase II study of daratumumab based therapies for older adults with 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 \/= 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) \