• Newly diagnosed patients with histologically confirmed multiple myeloma (MM) based on the IMWG diagnostic criteria and measurable disease within the past 4 weeks (or past 8 weeks if patient received pre-study MM therapy) based on one of the following:

‣ Serum monoclonal protein ≥ 1.0 g/dL

⁃ Urine monoclonal protein ≥ 200 mg/24 hour

⁃ Involved serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal kappa/lambda ratio

• Note:

⁃ Patients who have evaluable disease based on samples other than urine do not need to have urine evaluated for initial or subsequent response assessments.

⁃ Because the primary endpoint is MRD negativity rate, per the discretion of the Principal Investigator (PI), patients without measurable disease (e.g., M-spike \<1.0 g/dL) may also be enrolled in line with the International Myeloma Working Group (IMWG) MM response criteria.

• Evidence of underlying end organ damage and/or myeloma defining event attributed to underlying plasma cell proliferative disorder meeting at least one of the following (Note: Myeloma defining event does not need to be based on repeat testing done at screening if previous pathology, radiology, etc., confirm diagnosis of myeloma per IMWG):

‣ Hypercalcemia: serum calcium \>0.25 mmol/L (\>1.0 mg/dL) above upper limit of normal (ULN) or ≥2.75 mmol/L (11 mg/dL)

⁃ Anemia: hemoglobin value \<10 g/dL or \>2 g/dL below lower limit of normal (LLN)

⁃ Bone disease: ≥1 lytic lesions on skeletal X-ray, computed tomography (CT), or positron emission tomography (PET)-CT. For patients with 1 lytic lesion, bone marrow should demonstrate ≥10% clonal plasma cells

⁃ Clonal bone marrow plasma cell percentage ≥60%

⁃ Involved/un-involved serum free light chain ratio ≥100 and involved free light chain ≥100 mg/L.

⁃ \>1 focal lesion on magnetic resonance imaging study (lesion must be \>5 mm) in size

⁃ For patients with 1 lytic lesion, bone marrow should demonstrate ≥10% clonal plasma cells

• Patients must have measurable disease within the past 4 weeks, which is defined by any one of the following:

‣ Serum monoclonal protein ≥ 0.5 g/dL Urine monoclonal protein \>200 mg/24 hour

⁃ Serum immunoglobulin free light chain ≥10 mg/dL AND abnormal kappa/lambda serum free light chain ratio (reference: 0.26-1.65)

⁃ Other measurable disease as defined by the IMWG

⁃ Because the primary endpoint is MRD negativity based on bone marrow analysis, a patient without measurable disease in blood or urine may be enrolled and assessed for MRD negativity.

• Note:

⁃ Participants who have evaluable disease based on samples other than urine do not need to have urine evaluated for subsequent responses.

⁃ In participants who received minimal prior therapy within the allowable range per exclusion criteria 1, patients should have had documented measurable disease within 4 weeks of starting that respective therapy if currently unmeasurable.

• Adult male and female participants ≥ 18 years of age.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Refer to Appendix A)

• Participants must have adequate organ and marrow function ≤45 days as defined below:

‣ Absolute neutrophil count (ANC) \>1.0 K cells/μL; At the discretion of the Investigator, patients with an ANC of 0.5 K/μL-1.0 K/μL may also be enrolled if clinically appropriate (eg, patients with a baseline neutropenia that is chronic and/or ethnic neutropenia and that does not cause complications, e.g, no history of chronic infections).

⁃ Platelet count \>75 K cells/μL

⁃ Hemoglobin \>8 g/dL (transfusions are permissible if the cause of the anemia is other than myeloma)

⁃ Total bilirubin \<1.5 X upper limit of normal (ULN).

⁃ Note: Isolated total bilirubin ≥1.5 X ULN with conjugated \[direct\] bilirubin \<1.5 X ULN is allowed for those participants with known Gilbert's syndrome.

⁃ Aspartate aminotransferase (AST)/ alanine transaminase (ALT) ≤2.5 X ULN

⁃ GFR ≥30 mL/min based on Modification of Diet in Renal Disease (MDRD) 4-variable Formula calculation (Appendix 17.2) or creatine clearance (CrCl) measured by a 24-hour urine collection. (The estimated glomerular filtration rate (eGFR) may also be determined by using other widely accepted methods as clinically indicated, ie, Cockcroft-Gault method or the chronic kidney disease (CKD)-epidemiology collaboration (EPI) per institutional standards.

• Participants must be willing, able, and agree to enrolling in the lenalidomide Risk Evaluation and Mitigation Strategy (REMS) program.

• A female participant of childbearing potential must have a negative serum or urine pregnancy test at screening (at or within 45 days of study enrollment) and within 72 hours of the start of study treatment and must agree to further serum or urine pregnancy tests during the study

• A female participant must be:

‣ Not of childbearing potential, or

⁃ Of childbearing potential and practicing at least 1 highly effective method of contraception as described in Section 5.7

⁃ A female participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for at least 4 weeks after the last dose of lenalidomide or 4 months after the last dose of elranatamab. Female participants should consider preservation of eggs prior to study treatment, as anti-cancer treatments may impair fertility.

⁃ A female participant must agree to not breastfeed during the study and for a period of at least 4 weeks after the last dose of lenalidomide or 4 months after the last dose of elranatamab.

⁃ A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for a period of at least 4 weeks after receiving the last dose of study treatment. If the male participant's partner is a female of childbearing potential, the male participant must use condoms (with or without spermicide), and the female partner of the male participant must also be practicing a highly effective method of contraception. Refer to Section 5.7 for contraception requirements.

⁃ Note: If the male participant is vasectomized, he still must wear a condom (with or without spermicidal foam/gel/film/cream/suppository), but his female partner is not required to use contraception.

⁃ A male participant must agree not to donate sperm for the purpose of reproduction during the study and for period of 3 months after receiving the last dose of study treatment. Male participants should consider preservation of sperm prior to study treatment, as anti-cancer treatments may impair fertility.

⁃ Ability of the patient to understand and the willingness to sign a written informed consent document.

⁃ Have any condition that, in the opinion of the Investigator, would compromise the well-being of the patient or the study or prevent the patient from meeting or performing study requirements.

⁃ Must be willing and able to adhere to the lifestyle restrictions specified in this protocol.