• Documented multiple myeloma satisfying the International Myeloma Working Group (IMWG) diagnostic criteria36 (evidence of myeloma defining event attributed to underlying plasma cell disorder) with measurable disease defined as:

‣ Clonal plasma cells in the bone marrow ≥ 10% or presence of a biopsy proven plasmacytoma

⁃ Measurable disease within the past 4 weeks defined by any of the following:

• IgG myeloma: Serum monoclonal protein ≥ 1.0 g/dL or urine monoclonal protein ≥ 200 mg/24 hr; or

∙ IgA, IgM, IgD, IgE multiple myeloma: serum M-protein ≥ 0.5 g/dL or urine monoclonal protein ≥ 200 mg/24 hr; or

∙ Light chain multiple myeloma: Involved serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum free kappa/lambda light chain ratio

∙ Measurable plasmacytomas seen on imaging (≥ 1 lesion that has a single diameter ≥ 2 cm). If this is the primary marker of measurable disease, patients will need a biopsy at screening.

∙ Bone marrow plasma cells ≥ 30% as determined by CD138 immunohistochemistry staining.

• Standard risk multiple myeloma - excluding patients with high risk cytogenetic abnormality (HRCA) according to the IMS/IMWG 2024 Consensus Definition:

‣ TP53 mutation and/or del(17p) with cancer clonal function (CCF) \>20% by analyses conducted on CD138+ purified cells

⁃ t(4;14), t(14;16), or t(14;20) co-occurring with +1q (gain/amp 1q) and/or del(1p)

⁃ Monoallelic del(1p32) with +1q or biallelic del(1p32)

⁃ High Beta-2 microglobulin (\>5.5 mg/dL) with normal creatinine (\<1.2 mg/dL)

• Newly diagnosed patient considered a candidate for high-dose chemotherapy and autologous stem cell transplant

• Age ≥18 years.

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

• Have adequate organ and hematologic function:

‣ Hemoglobin ≥ 7.5 g/dL (prior RBC transfusion or recombinant human erythropoietin use is permitted);

⁃ Absolute neutrophil count (ANC) ≥ 1.0 x 109/L (G-CSF use is permitted);

⁃ Platelet count ≥ 75 x 109/L

⁃ Creatinine Clearance ≥ 30 ml/min. CrCl can be measured or estimated using Cockcroft-Gault method, MDRD, or CKD-EPI formula

⁃ Total bilirubin ≤ 2 x ULN (≤ 3 x ULN if documented Gilbert's syndrome);

⁃ AST ≤ 2.5 x ULN;

⁃ ALT ≤ 2.5 x ULN

• All study participants must be able to tolerate one of the following thromboprophylaxis strategies: aspirin, low molecular weight heparin or warfarin (coumadin) or alternative anti-coagulant.

• All study participants must be able to tolerate one of the following thromboprophylaxis strategies: aspirin, low molecular weight heparin or warfarin (Coumadin), or direct-acting oral anticoagulants (DOACs).

• All study participants must be registered into the mandatory REMS® program and be willing and able to comply with the requirements of REMS®, including compliance with contraception methods (Appendix A).