Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone in NDMM

Inclusion Criteria:

• Previously diagnosed with MM based on standard IMWG criteria and currently requirestreatment.

• Provided voluntary written informed consent before performance of any study-relatedprocedures not part of normal medical care, with the understanding that consent maybe withdrawn by the patient at any time without prejudice to their future medicalcare

• Age ≤ 75 years, with patients over the age of 70 requiring PI approval

• Measurable disease defined as at least one of the following:

• Serum M protein ≥ 0.5 g/dL (≥5 g/L)

• Urine M protein ≥ 200 mg/24 hours

• Serum free light chain (FLC) assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L)and an abnormal serum FLC ratio (<0.26 or >1.65)

• Screening Laboratory evaluations within the following parameters

• Absolute neutrophil count (ANC) ≥ 1,000 cells/dL (1.0 x 109/L) (Growth factorscannot be used within 14 days before first drug administration)

• Platelet count ≥ 75,000 cells/dL (75 x 109/L) if < 50% BM nucleated cells areplasma cells, ≥ 30,000 cells/dL if ≥ 50% of BM nucleated cells are plasmacells. (without transfusions required during the 3 days prior to the screeninghematologic test)

• Total Bilirubin ≤ 2.0 X upper limit of normal (ULN) (except patients withGilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)

• AST (SGOT) and ALT (SGPT) ≤ 3.0 x ULN

• Calculated creatinine clearance ≥ 30 mL/min

• Hemoglobin ≤ 8 g/dL

• ECOG performance status ≤ 2 (Appendix A)

• Participant agrees to be registered into the mandatory Revassist REMS® program, andbe willing and able to comply with the requirements of the RevAssist REMS® program.

• Ability to understand and the willingness to sign a written informed consentdocument

• Participant is considered eligible for ASCT by the treating physician.

Exclusion Criteria:

• Prior therapy for multiple myeloma

• Diagnosed or treated for another malignancy within 3 years prior to enrollment, withthe exception of complete resection of basal cell carcinoma or squamous cellcarcinoma of the skin, an in-situ malignancy, or low risk prostate cancer aftercurative therapy.

• Central nervous system involvement.

• Peripheral neuropathy ≥ Grade 3, or Grade 2 with pain on clinical examination duringthe screening period.

• Any medical or psychiatric illness that in the Investigator's opinion, would imposeexcessive risk to the patient or would adversely affect his/her participating inthis study.

• Concurrent uncontrolled cardiovascular conditions, including uncontrolledhypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heartfailure, unstable angina, Grade 3 thromboembolic event or myocardial infarctionwithin the past 6 months.

• Prior major surgical procedure or radiation therapy within 4 weeks of initiation oftherapy (this does not include limited course of radiation used for management ofbone pain within 7 days of initiation of therapy).

• Daily requirement for corticosteroids (equivalent to > 10 mg/day prednisone for morethan 7 days (except for inhalation corticosteroids).

• Concurrent symptomatic amyloidosis or plasma cell leukemia

• POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly,endocrinopathy, monoclonal protein and skin changes)

• Known active infection requiring parenteral or oral anti-infective treatment within 14 days of start of therapy.

• Active hepatitis B or hepatitis C viral infection

• Pregnant or breastfeeding female or female who intends to become pregnant during theparticipation in the study. Females of childbearing potential (FCBP) unwilling toprevent pregnancy by the use of 2 reliable methods of contraception for ≥4 weeksbefore the start of study treatment, during treatment (including doseinterruptions), and up to 3 months following the last dose of study treatment and/orwho are unwilling or unable to be tested for pregnancy before study treatmentinitiation (2 negative tests), weekly during 1st month of treatment and then prioreach treatment cycle administration or every 2 weeks in case or irregular menstrualcycles up to 3 months following the last dose of study treatment.

• Male participants who disagree to practice true abstinence or disagree to use acondom during sexual contact with a pregnant female or a FCBP while participating inthe study, during dose interruptions and at least 3 months following study treatmentdiscontinuation, even if has undergone a successful vasectomy.

• Note 1: a FCBP is a female who: 1) has achieved menarche at some time point, 2)has not undergone a hysterectomy or bilateral oophorectomy or 3) has not beennaturally postmenopausal (amenorrhea following cancer therapy does not rule outchildbearing potential) for at least 24 consecutive months (ie, has had mensesat any time in the preceding 24 consecutive months).

• Note 2: True abstinence is acceptable when this is in line with the preferredand usual lifestyle of the patient. Periodic abstinence (eg, calendar,ovulation, symptothermal, post-ovulation methods) and withdrawal are notacceptable methods of contraception.

• Receiving any other investigational agents

• Inability to tolerate thromboprophylaxis

• Hypersensitivity (or contraindication) to dexamethasone, sucrose histidine (as baseand hydrochloride salt), boron, mannitol, and polysorbate 80, or to any of thecomponents of the study therapy

• Hypersensitivity to steroids or H2 blockers that would prohibit further treatmentwith these agents.