MRD-Adapted Elranatamab for the Treatment of Relapsed and Refractory Multiple Myeloma

Inclusion Criteria

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Prior diagnosis of relapsed/refractory multiple myeloma (MM) and have received 1 to 3 prior lines of therapy as defined by the International Myeloma Working Group (IMWG) criteria (Rajkumar et al., 2014) including anti-CD38 monoclonal antibody, proteosome inhibitor (PI), and immunomodulatory drug (IMiD) * Refractory is defined as having disease progression while on therapy or within 60 days of last dose in any line, regardless of response
• Aged greater or equal to 18 years
• Measurable disease as defined by any of the following: * Serum M-protein level ≥ 0.5 g/dL by serum protein electrophoresis (SPEP), or * Urine M-protein ≥ 200mg/24 hours by urine protein electrophoresis (UPEP), or * Involved serum free light chain ≥ 10 mg/dL (≥ 100mg/L) AND an abnormal serum free light chain ratio in patients without measurable disease in the serum or urine
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Absolute neutrophil count (ANC) ≥ 1,000/mm^3 (granulocyte colony-stimulating factor [G-CSF] not permitted for at least 1 week prior to the first dose of elranatamab)
• Hemoglobin ≥ 8.0 g/dL (transfusion support is permitted if completed at least 1 week prior to planned start of dosing)
• Platelet count ≥ 75,000/mm^3 or ≥ 50,000/mm^3 if > 50% involvement with plasma cells in the screening bone marrow (transfusion support is permitted if completed at least 1 week prior to planned start of dosing)
• Adequate renal function with estimated creatinine clearance (CrCl) ≥ 30 mL/min as calculated using Cockcroft-Gault equation
• Aspartate and alanine aminotransferase (AST and ALT) ≤ 2.5 x upper limit of normal (ULN); ≤ 5.0 x ULN if there is liver involvement by the tumor
• Alkaline phosphatase ≤ 2.5 x ULN (≤ 5 x ULN in case of bone metastasis)
• Total bilirubin ≤ 2.0 mg/dL, except in patients with Gilbert syndrome who must have a total bilirubin less than 3.0 mg/dL
• Able to receive outpatient treatment of elranatamab by meeting the following criteria: * Lives within 30 minutes from the site of medication administration * Reliable caregiver present, who is able to watch participant continuously for at least until 48 hours after administration of first full treatment dose * No history of grade 3-4 cytokine release syndrome (CRS) or grade 3-4 immune effector cell-associated neurotoxicity syndrome (ICANS) from other immune effector cell or bispecific antibody therapies
• Resolved acute effects of any prior therapy to baseline severity or Common Terminology Criteria for Adverse Events (CTCAE) grade ≤ 1
• Serum pregnancy test (for females of childbearing potential) negative at screening * Female patients of non-childbearing potential must meet at least 1 of the following criteria: ** Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed with a serum follicle stimulating hormone (FSH) level confirming the postmenopausal state ** Have undergone a documented hysterectomy and/or bilateral oophorectomy ** Have medically confirmed ovarian failure * All other female patients (including female patients with tubal ligations) are considered to be of childbearing potential
• Agreement to adhere to lifestyle considerations throughout study duration

Exclusion Criteria

• Subjects with smoldering multiple myeloma, immunoglobulin M (IgM) multiple myeloma, Waldenstrom’s macroglobulinemia, amyloidosis, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, and primary and secondary plasma cell leukemia, defined as circulating plasma cells ≥ 5%
• Extramedullary relapse who does not meet criteria for measurable disease as above
• Active malignancy other than multiple myeloma requiring treatment in the past 3 years, with the exception of successfully treated non-metastatic squamous or basal skin carcinoma
• Known central nervous system (CNS) involvement by multiple myeloma
• Active, uncontrolled autoimmune disorders
• Active uncontrolled infection. Active infections must be resolved and/or controlled at least 14 days prior to enrollment
• Radiation therapy within 2 weeks prior to study entry (bone lesions requiring radiation may be treated with limited [ie, ≤ 25% of bone marrow in field] radiation therapy during this period)
• Last systemic treatment within 2 weeks or 5 half lives, whichever is shorter. Subjects can receive a maximum of 160mg of dexamethasone or equivalent during screening, but at least 7 days prior to start of therapy
• Last radiation treatment to multiple sites within 2 weeks and single site within 1 week
• History of autologous stem cell transplant within 100 days prior to study enrollment
• History of allogeneic transplant within 1 year prior to study enrollment or active graft versus host disease
• On immunosuppressive therapy for concurrent comorbid conditions
• Other major uncontrolled medical comorbidities that may put patients at risk of serious adverse event with treatment with study medication
• Clinically significant, uncontrolled cardiac disease
• Grade ≥ 2 peripheral sensory or motor neuropathy
• History of Guillan-Barre syndrome
• Other surgical (including major surgery within 14 days prior to enrollment) or psychiatric conditions including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study
• Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer)
• Pregnancy or lactation
• Known or suspected hypersensitivity to the study intervention or any of its excipients