Pre-transplant Purging and Post-transplant MRD-guided Maintenance Therapy With Elranatamab in Patients With High-risk Multiple Myeloma

Inclusion Criteria: 1. Transplant eligible patients with newly diagnosed multiple myeloma (NDMM). 2. High-risk multiple myeloma\* 3. Participants with disease response ≥ PR to induction therapy 4. Age ≥ 18 and ≤ 75. Non-English-speaking participants are eligible. 5. Karnofsky performance status ≥70 (Appendix A). 6. Adequate liver function (total bilirubin ≤1.5X ULN; ALT ≤2.5 X ULN) 7. Estimated creatinine clearance ≥40 mL/min. Creatinine clearance may be calculated using Cockcroft-Gault, estimated glomerular filtration rate (Modification of Diet in Renal Disease \[MDRD\]), or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula). \* 8. Participant agrees to not donate blood while taking lenalidomide and for 28 days after stopping lenalidomide. 9. Participant agrees to enroll in the lenalidomide REMS program. 10. Women of child-bearing potential (WOCPB) must abstain from heterosexual intercourse or agree to use a contraceptive method that is highly effective (with a failure rate of \<1% per year), preferably with low user dependency (as described in Appendix B), plus one additional effective method at least 28 days before starting therapy, during the intervention period, at least 28 days after the last dose of lenalidomide and at least 4 months after the last dose of elranatamab, and agrees not to donate eggs (ova, oocytes) for reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relation to the first dose of the study intervention. A WOCBP must have a negative highly sensitive serum pregnancy test (as required by local regulations) within 10-14 days and also within 24 hours before the first dose of the study intervention. Non Nonchildbearing potential is defined as follows (by other than medical reasons): * ≥ 45 years of age and has not had menses for \>1 year. * Participants who have been amenorrhoeic for \<2 years without a history of a hysterectomy and oophorectomy must have a follicle-stimulating hormone value in the postmenopausal range upon screening evaluation. * Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. 11. Male participant agrees to contraceptive use that should be consistent with institutional guidelines regarding the methods of contraception for those participating in clinical studies. * Male participants are eligible to participate if they agree to the following during the intervention period and for 1 (for lenalidomide) to 4 (for elranatamab) months after the last dose of study treatment to allow for clearance of any altered sperm: - Refrain from donating sperm during treatment (including dose interruptions) and for 4 weeks after their last dose of lenalidomide and 4 months after the last dose of elranatamab. PLUS, either: * Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent. OR * Must agree to use contraception/barrier as detailed in Appendix B. \*Definition of high-risk and ultra-high-risk MM15: * High-risk MM: o Presence of a high-risk chromosomal abnormality (HRCA) including: 17p13 deletion; t(4;14); t(14;16); t(14;20); Gain or amplification 1q by FISH. * Ultra-high-risk MM * Presence of ≥2 HRCA. Exclusion Criteria: • History of allergic reactions attributed to compounds of similar chemical or biologic composition to elranatamab or other agents used in study. • Drug interactions (Prohibited unless considered medically necessary): a. At projected clinical doses, TMDD (target mediated drug disposition) of elranatamab is expected. If concomitant medication alters target expression, it can potentially impact the PK of elranatamab. Drugs like anti-thymocyte globulin (ATG) can deplete T-cells and can potentially impact the PK of drugs targeting CD3. b. Elranatamab has been shown to increase T-cell activation and induce cytokine production (including IL-2, IL-6, IL-10, TNF-alpha and IFN-gamma). Cytokines have been shown to modulate expression of CYP enzymes and transporters, therefore, elranatamab can potentially affect CYP enzyme and transporter expression levels, and consequently modulate the clearance of concomitant medications that are substrates for these enzymes or transporters. When administering elranatamab, it is important to exercise caution with concomitant medications, especially those that are sensitive substrates of the cytochrome P450 (CYP) enzyme system and have a narrow therapeutic index. Increased exposure of CYP substrates is more likely to occur after the first dose of elranatamab on Day 1 and up to 14 days after the 32 mg dose on Day 4 and during and after CRS. Examples of such medications include cyclosporine. During this critical window, it's imperative to closely monitor the toxicity or concentrations of these concomitant drugs. If necessary, dose adjustments for these co-administered drugs should be considered to ensure patient safety. c. Cytochrome P450 (CYP) enzyme system is responsible for the metabolism of a vast number of drugs. Below are examples of drugs metabolized by specific CYP enzymes that could be impacted if elranatamab alters the activity or expression of these enzymes. Exercise caution when using these drugs: i. CYP2C9 substrates: <!-- --> 1. \- Warfarin 2. \- Phenytoin 3. \- Celecoxib 4. \- Losartan ii. CYP3A4 substrates: <!-- --> 1. \- Statins: simvastatin, atorvastatin, lovastatin 2. \- Calcineurin inhibitors: cyclosporine, tacrolimus 3. \- Antiretroviral drugs: ritonavir, saquinavir, nelfinavir 4. \- Benzodiazepines: diazepam, alprazolam 5. \- Calcium channel blockers: nifedipine, verapamil, diltiazem 6. \- Macrolide antibiotics: erythromycin, clarithromycin iii. CYP2D6 substrates: <!-- --> 1. \- Antipsychotics: aripiprazole, risperidone, haloperidol 2. \- Tricyclic antidepressants: amitriptyline, nortriptyline, imipramine 3. \- Beta-block