Pharmacodynamically Monitored Linvoseltamab Dosing De-Escalation in Relapsed Multiple Myeloma

Inclusion Criteria: * Age ≥ 18 years. Myeloma is not seen in the younger age group and safety of B-cell maturation antigen (BCMA) T-cell engagers (TCE) in this group is not known * Ability to understand and willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of potential study participants * Confirmed diagnosis of active multiple myeloma (MM) by International Myeloma Working Group (IMWG) diagnostic criteria * Patients must have myeloma that is measurable and response evaluable according to 2016 IMWG response criteria. Measurable disease is defined as one of the following, documented ≤ 14 days prior to registration: * Serum M protein ≥ 1 g/dl * Urine M protein ≥ 200 mg/24h * Free light chain (FLC) assay with involved FLC ≥ 10 mg/dl and abnormal FLC ratio * A patient with immunoglobulin A (IgA) MM without measurable M protein may be enrolled if quantitative (quant) IgA level ≥ 400 mg/dl and can be followed longitudinally * Plasmacytoma target lesion defined as measurable based on at least 1 soft tissue lesion ≥ 2 cm in long axis on CT or PET/CT, if not previously irradiated * Skin lesions ≥ 2 cm in long axis as measured with a ruler * Patients with relapsed or refractory myeloma who have received at least 4 prior lines of therapy including proteasome inhibitor (PI), immunomodulatory imide drug (IMiD), and anti-CD38 monoclonal antibody * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 * Adequate organ function (based on testing ≤14 days prior to registration): * Adequate hematologic function before dosing as measured by: * Platelet count ≥50 x 10⁹/L. A patient may not have received a platelet transfusion ≤7 days in order to meet this platelet eligibility requirement * Absolute neutrophil count (ANC) ≥1.0 x 10⁹/L. A patient may not have received granulocyte colony stimulating factor (G-CSF) ≤2 days in order to meet this absolute neutrophil count eligibility requirement * Hemoglobin ≥8.0 g/dL * Adequate renal and hepatic function, defined as: * Total bilirubin ≤1.5 x ULN * Transaminase (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\]) ≤2.5 x ULN * Alkaline phosphatase ≤2.5 x ULN * Patients with Gilbert syndrome do not need to meet this total bilirubin requirement provided that the total bilirubin is unchanged from the baseline value * Serum creatinine clearance by Cockcroft-Gault ≥30 mL/min. A patient with a creatinine clearance by Cockcroft-Gault who does not meet eligibility criteria may be considered for enrollment per principal investigator discretion if a measured creatinine clearance (based on 24-hour urine collection or other reliable method) is ≥30 mL/min * Prior treatment with BCMA-targeted antibody-drug conjugates (ADCs) is allowable if all adverse events (AEs) attributable to these therapies have resolved to grade 1 or lower * Willing and able to comply with clinic visits and study-related procedures and provide informed consent signed by study patient Exclusion Criteria: * Diagnosis of known plasma cell leukemia, known primary systemic light-chain amyloidosis (excluding myeloma-associated amyloidosis), known Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or known POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) * Patients with known MM brain lesions or meningeal involvement * History of known neurodegenerative condition, central nervous system (CNS) movement disorder, or patients with a history of seizure within 12 months prior to study enrollment * Continuous systemic corticosteroid treatment with more than 10 mg per day of prednisone or anti-inflammatory equivalent within 72 hours of start of study drug * Live or live attenuated vaccines with replicating potential within 28 days prior to first study drug administration * Previous treatment with chimeric antigen receptor (CAR) T therapy or any gene therapy products * Any infection requiring hospitalization or treatment with intravenous (IV) anti-infectives within 2 weeks of first administration of study drug * Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C (HCV) * Known allergy or hypersensitivity to components of linvoseltamab (REGN5458) * Women of childbearing potential (WOCBP) with a positive serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test are ineligible for this study * WOCBP are defined as women who are fertile following menarche until becoming postmenopausal, unless permanently sterile. Post-menopausal state is defined as no menses for 12 months without an alternate medical cause * Participants who are receiving other investigational agents * Women of childbearing potential (WCOBP) and men who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose * Uncontrolled or concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Another malignancy in the past 5 years, except for non-melanoma skin cancer that has undergone potentially curative therapy or in situ cancer, or any other tumor that has been deemed to be effectively treated with definitive local control and with curative intent