Elranatamab in Relapsed/Refractory Multiple Myeloma

Eligibility Criteria

• 1. Provision of signed and dated informed consent form
• 2. Stated willingness to comply with all study procedures and availability for the duration of the study
• 3. Prior diagnosis of relapsed/refractory MM and have received 1 to 3 prior lines of therapy as defined by the IMWG criteria (Rajkumar et al., 2014) including anti-CD38 monoclonal antibody, proteosome inhibitor (PI), and immunomodulatory drug (IMiD), and BCMA-directed chimeric antigen receptor T-cell (CAR T-cell) therapy
• 1. Refractory is defined as having disease progression while on therapy or within 60 days of last dose in any line, regardless of response.
• 2. If participant has not received BCMA-directed CAR T-cell therapy, must be ineligible for CAR T-cell therapy or deferred such treatment by participant
• 4. Aged greater or equal to 18 years
• 5. Measurable disease as defined by any of the following:
• 1. Serum M-protein level ≥ 0.5 g/dL by serum protein electrophoresis (SPEP), or
• 2. Urine M-protein ≥ 200mg/24 hours by urine protein electrophoresis (UPEP), or
• 3. 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
• 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• 7. Adequate hematological function defined as
• 1. Absolute neutrophil count (ANC) ≥1,000/mm3 (G-CSF not permitted for at least 1 week prior to the first dose of elranatamab)
• 2. Hemoglobin ≥8.0 g/dL (transfusion support is permitted if completed at least 1 week prior to planned start of dosing)
• 3. Platelet count ≥75,000/mm3 or ≥50,000/mm3 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)
• 8. Adequate renal function with estimated creatinine clearance (CrCl) ≥30 mL/min as calculated using Cockcroft-Gault equation.
• 9. Adequate liver function defined as
• 1. 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.
• 2. Alkaline phosphatase ≤2.5 x ULN (≤5 x ULN in case of bone metastasis).
• 3. Total bilirubin ≤2.0 mg/dL, except in patients with Gilbert Syndrome who must have a total bilirubin less than 3.0 mg/dL.
• 10. Able to receive outpatient treatment of elranatamab by meeting the following criteria:
• 1. Lives within 30minutes from the site of medication administration
• 2. Reliable caregiver present, who is able to watch participant continuously for at least until 48 hours after administration of first full treatment dose
• 3. No history of grade 3-4 CRS or grade 3-4 ICANS from other immune effector cell or bispecific antibody therapies
• 11. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1
• 12. Serum pregnancy test (for females of childbearing potential) negative at screening.
• 13. Agreement to adhere to Lifestyle Considerations (see section 5.3 and Appendix 2) throughout study duration
• 1. Subjects with smoldering multiple myeloma, IgM multiple myeloma, Waldenstrom's macroglobulinemia, amyloidosis, POEMS syndrome, and primary and secondary plasma cell leukemia, defined as circulating plasma cells ≥ 5%
• 2. Extramedullary relapse who does not meet criteria for measurable disease as above
• 3. 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
• 4. Known CNS involvement by multiple myeloma
• 5. Active, uncontrolled autoimmune disorders
• 6. Active uncontrolled infection. Active infections must be resolved and/or controlled at least 14 days prior to enrollment.
• 7. 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).
• 8. 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.
• 9. Last radiation treatment to multiple sites within 2 weeks and single site within 1 week
• 10. History of autologous stem cell transplant within 100 days prior to study enrollment.
• 11. History of allogeneic transplant within 1 year prior to study enrollment or active graft versus host disease.
• 12. On immunosuppressive therapy for concurrent comorbid conditions
• 13. Other major uncontrolled medical comorbidities that may put patients at risk of serious adverse event with treatment with study medication.
• 14. Clinically significant, uncontrolled cardiac disease
• 15. Grade ≥2 peripheral sensory or motor neuropathy
• 16. History of Guillan-Barre syndrome
• 17. 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.
• 18. 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).
• 19. Pregnancy or lactation
• 20. Known or suspected hypersensitivity to the study intervention or any of its excipients.