Registration Step 1 Except where otherwise indicated below that test is required in a shorter timeframe, all tests for establishing baseline disease status must be completed within 60 days prior to registration. All test results must be documented on the Baseline Tumor Assessment Form for Multiple Myeloma and the Onstudy Form:

Patients must have had a confirmed diagnosis of symptomatic multiple myeloma (See Section 4.1) that required systemic induction therapy prior to autologous stem cell transplantation (ASCT)

Patients with disease measurable by serum light chain assay alone are eligible (defined as = > 100 mg/L on involved light chain)

Patients must be registered to Step 1 prior to registration to Step 2. Registration to Step 1 may take place prior to or after autologous stem cell transplant (ASCT), but after completion of induction therapy

Patients must have initiated induction therapy within 12 months prior to registration Step 1 and have received at least two cycles of induction therapy

Patients must be willing and able to take DVT prophylaxis (aspirin, low molecular weight heparin, warfarin, or equivalent oral anticoagulation)

Patients must be = >18 and = <75 years of age at time of registration to Step 1

Patients must have history and physical exam within 28 days prior to registration

Please contact study team for additional inclusion/exclusion criteria

Patients with smoldering myeloma are not eligible. Patients with purely non-secretory MM as measured by electrophoresis and immunofixation and the absence of Bence Jones proteins in the urine are not eligible.

Patients must have measurable M protein in the serum (defined as = > 0.5g/dL) or urine (defined as = >200 mg/24h). Patients with plasma cell leukemia are not eligible

Patients must not have any organ involvement by amyloidosis or evidence of amyloidosis related organ dysfunction

Patients must not have progressive disease at any time prior to registration

Patients must not be refractory to either lenalidomide or daratumumab/rHuPH20

Patients must not be intolerant to either lenalidomide or daratumumab/rHuPH20

Patients must not have received any investigational agents within 14 days prior to registration

Please contact study team for additional inclusion/exclusion criteria

• Blood Protein Disorders

• Cardiovascular Diseases

• Hematologic Diseases

• Hemorrhagic Disorders

• Hemostatic Disorders

• Immune System Diseases

• Immunoproliferative Disorders

• Lenalidomide

• Lymphoproliferative Disorders

• Multiple Myeloma

• Neoplasms

• Neoplasms by Histologic Type

• Neoplasms, Plasma Cell

• Paraproteinemias

• Vascular Diseases

• Oncology (Adult)

• National Cancer Institute (NCI)