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.
• •• Participant must not have current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable non-cirrhotic chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if otherwise meets entry criteria.
• •• Uncontrolled and active pulmonary disease.
• •• Participant must not have used an investigational drug or approved systemic anti-myeloma therapy (including systemic steroids) within 14 days or five half-lives, whichever is shorter, preceding the first dose of study drug.
• •• Participant must not have any evidence of active mucosal or internal bleeding.
• •• Participant must not have an uncontrolled infection.
• •• Participant must not have evidence of cardiovascular risk, including any of the following:
• •* Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Mobitz Type II) or 3rd degree atrioventricular (AV) block.
• •* History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within three (3) months of screening.
• •* Class III or IV heart failure as defined by the New York Heart Association functional classification system.16
• •* Uncontrolled hypertension (blood pressure that remains above goal despite the concurrent use of three antihypertensive drug classes). • Participant must not have known HIV infection. • Participant must not have active Hepatitis B and/or C infection. • Participant must not have invasive malignancies other than disease under study, unless the second malignancy has been medically stable for at least 2 years and, in the opinion of the principal investigators, will not affect the evaluation of the effects of clinical trial treatments on the currently targeted malignancy. Participants with curatively treated non-melanoma skin cancer may be enrolled without a 2-year restriction. • Participants must not be pregnant or lactating. • Patients with cognitive impairments and/or any serious unstable pre-existing medical condition or psychiatric disorder that can interfere with safety or with obtaining informed consent or compliance with study procedures.