This is a multicenter, single arm, open-label, Phase 2 study in mutiple myeloma with newly diagnosed and treatment-naïve participants for whom high-dose therapy and autologous stem cell transplantation is part of the intended treatment plan. The study is evaluating a technique called Mass Spectrometry Minimal Residual Disease (MS-MRD) using blood samples and compares it with the minimal residual disease (MRD) technique using bone marrow samples.

Inclusion Criteria:

• 18 to 70 years of age, inclusive.
• Must have a new diagnosis of MM as per IMWG criteria.
• Measurable disease
• Newly diagnosed and treatment-naïve participants for whom high-dose therapy and autologous stem cell transplantation is part of the intended treatment plan.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2.
• Clinical laboratory values meeting the required criteria during screening and ≤3 days prior to receiving first study treatment dose.
• Adequate bone marrow function.
• Adequate liver function.
• Adequate renal function.
• A female of childbearing potential (FOCBP) must have two negative serum or urine pregnancy tests at screening including within 24 hours of the start of study treatment.
• Willing to practicing at least 1 highly effective method of contraception starting 4 weeks prior to start of study treatment, while receiving study treatment including during any dose interruptions, and for at least 3 months after the last dose of any component of the study treatment.

Exclusion Criteria:

• Prior or current systemic therapy or ASCT for any plasma cell dyscrasia, with the exception of emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment.
• History of allogenic stem cell transplantation or prior organ transplant requiring immunosuppressive therapy.
• Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.
• Myelodysplastic syndrome or any malignancy within 24 months of signing consent. The only exceptions are malignancies treated within the last 24 months that are considered completely cured.
• Plasmapheresis ≤28 days of approval.
• Radiation therapy for treatment of plasmacytoma ≤14 days of approval of enrollment.
• Forced Expiratory Volume in 1 second (FEV1) <50% of predicted normal.
• Concurrent medical or psychiatric condition or disease.
• Myocardial infarction ≤6 months of enrollment, or an unstable or uncontrolled disease/condition related to or affecting cardiac function.
• Uncontrolled cardiac arrhythmia or clinically significant electrocardiogram (ECG) abnormalities.
• Allergy, hypersensitivity, or intolerance to boron or mannitol, corticosteroids, monoclonal antibodies or human proteins, or the excipients of daratumumab, lenalidomide, bortezomib or dexamethasone.
• Pregnant or breast-feeding females