In the absence of coverage criteria from applicable Medicare statutes, regulations, NCDs, LCDs, CMS manuals, or other Medicare coverage documents, this policy uses internal coverage criteria developed by the Company in consideration of peer-reviewed medical literature, clinical practice guidelines, and/or regulatory status.
The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.
MEDICALLY NECESSARY
Elranatamab-bcmm (Elrexfio) injection is considered medically necessary and, therefore, covered as a single agent in adult individuals with refractory or relapsed multiple myeloma (RRMM) who have received at least four prior therapies, including a proteasome inhibitor (e.g., bortezomib, carfilzomib, ixazomib), an immunomodulatory agent (e.g., thalidomide, lenalidomide, pomalidomide), and an anti-CD38 monoclonal antibody (isatuximab-irfc, daratumumab) as National Comprehensive Cancer Network (NCCN)-preferred therapy.
The above regimens may also be used for the treatment of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) (useful in certain circumstances), monoclonal immunoglobulin deposition disease (MIDD), and plasma cell–related monoclonal gammopathy of renal significance (MGRS).
EXPERIMENTAL/INVESTIGATIONALAll other uses for elranatamab-bcmm (Elrexfio) not identified in this policy are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.
REQUIRED DOCUMENTATIONThe individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.
There is no Medicare coverage determination addressing elranatamab-bcmm (Elrexfio); therefore, the Company policy is applicable.
BLACK BOX WARNINGS
Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.
BENEFIT APPLICATION
Subject to the applicable Evidence of Coverage, elranatamab-bcmm (Elrexfio) is covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria listed in the medical policy are met.
For Medicare Advantage members, certain drugs are available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when elranatamab-bcmm (Elrexfio) is covered under a member's medical benefit (Part B benefit). It does not address instances when elranatamab-bcmm (Elrexfio) is covered under a member's pharmacy benefit (Part D benefit).
US FOOD AND DRUG ADMINISTRATION (FDA) STATUS
Elranatamab-bcmm (Elrexfio) was approved by the FDA on August 14, 2023, for the treatment of adult individuals with relapsed or refractory multiple myeloma, who previously received four or more prior lines of therapy, including a proteasome inhibitor, immunomodulatory drug, and anti-CD38 monoclonal antibody.
PEDIATRIC USE
The safety and effectiveness of elranatamab-bcmm (Elrexfio) have not been established in pediatric individuals less than 18 years of age.
HOSPITAL ADMISSION FOR ADMINISTRATION When the medical necessity criteria has been met, the hospital admission for first cycle administration of elranatamab-bcmm (Elrexfio), as recommended by the US Food and Drug Administration (FDA), is covered in accordance with the following timeframes*:
First cycle: Individuals should be hospitalized for 48 hours after administration of the first step-up dose, and for 24 hours after administration of the second step-up dose due to the risk of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS)
*Hospital stays that are longer than the preceding timeframes must be re-evaluated for medical necessity.
Multiple myeloma is a cancer of plasma cells. Healthy plasma cells grow and divide to make new cells; once cells grow old or get damaged, they die. Because of the genetic variations in multiple myeloma, the myeloma cells replicate uncontrollably throughout the bone marrow, do not die when they get old or damaged, outnumber normal blood cells in the bone marrow, and destroy the bone tissue. The antibodies synthesized by myeloma cells do not fight infections in the same way as normal antibodies do. Multiple myeloma symptoms include low blood counts that cause anemia, bone pain, kidney damage due to elevated creatinine or serum protein, infection, fatigue, and hypercalcemia.
Nearly all individuals with multiple myeloma who receive standard therapies experience relapse. Those with triple-class–refractory multiple myeloma (i.e., disease that is refractory to a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody) or relapsed multiple myeloma who receive standard treatment have a poor prognosis. Therefore, there is a high demand for agents that treat multiple myeloma in individuals who do not respond, or who progress after first- or subsequent-line therapy.
Elranatamab-bcmm (Elrexfio) is a bispecific T-cell engager (BiTE) that binds on T cells and to B-cell maturation antigen (BCMA)-directed CD3 expressed on the surface of myeloma cells and some healthy B-lineage cells.
PEER-REVIEWED LITERATURE
SUMMARY
Safety and efficacy were evaluated in a phase II, MagnetisMM-3 trial: patients with relapsed/refractory multiple myeloma received subcutaneous elranatamab once weekly. The primary population in whom efficacy was seen were patients (n=123) without prior BCMA-directed therapy. The findings indicated an objective response rate (ORR) of 61.0% (75/123) and 35.0% greater than or equal to complete response (CR). Fifty responders switched to biweekly dosing, and 40 of those (80.0%) improved or maintained their response for 6 months or more. Common adverse events reported were infections, cytokine release syndrome, anemia, and neutropenia. With biweekly dosing, grade 3–4 adverse events decreased from 58.6% to 46.6%.
OFF-LABEL INDICATIONS
There may be additional indications contained in the Policy section of this document due to the evaluation of criteria highlighted in the Company's off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
American Cancer Society [website]. Multiple Myeloma. Revised 02/2/2018. Available at: https://www.cancer.org/cancer/types/multiple-myeloma/about/what-is-multiple-myeloma.html. Accessed March 5, 2026.
American Hospital Formulary Service (AHFS). Drug Information. 2024. Elranatamab-bcmm. [LexiDrugs website]. 12/12/2025. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 5, 2026.Elsevier's Clinical Pharmacology Compendium. Elranatamab-bcmm (Elrexfio). [Clinical Key Web site]. 08/24/25. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed March 5, 2026.Lexi-Drugs Compendium. Elranatamab-bcmm. [Lexicomp Online Web site]. 02/24/2026. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 5, 2026.Micromedex® Healthcare Series [Internet database]. Elranatamab-bcmm. Greenwood Village, CO: Thomson Micromedex. 01/22/2026. Available at: http://www.micromedexsolutions.com/micromedex2/librarian. Accessed March 5, 2026.
Lesokhin AM, Tomasson MH, Arnulf B, et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat Med. 2023;29:2259-2267.National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology – Multiple Myeloma. V5.2026. [NCCN Web site]. 01/09/2026. Available at: https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf [via subscription only]. Accessed March 5, 2026.
National Comprehensive Cancer Network (NCCN). NCCN Drugs and Biologics Compendium. Elranatamab-bcmm. [NCCN Web site]. 2026. Available at: https://www.nccn.org/professionals/drug_compendium/content/Reports/Report.aspx?DrugCompendiumIds=359025 [via subscription only]. Accessed March 5, 2026. US Food and Drug Administration (FDA). Elranatamab-bcmm (Elrexfio) prescribing information & approval letter. [FDA Web site]. 02/2026. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761345Orig1s000lbl.pdf. Accessed March 5, 2026.
C90.00 Multiple myeloma not having achieved remission
C90.02 Multiple myeloma in relapse
C90.20 Extramedullary plasmacytoma not having achieved remission
C90.22 Extramedullary plasmacytoma in relapse
Revisions From MA08.168a:
05/04/2026
This version of the policy will become effective 05/04/2026.
Per National Comprehensive Cancer Network (NCCN) Category 2A recommendations, elranatamab-bcmm (Elrexfio) has been updated to reflect the applicability of these regimens in select cases of POEMS, MIDD, and MGRS.
All of the ICD-10 CM codes have been removed from this policy. Report the most appropriate diagnosis code in support of medically necessary criteria as listed in the policy.
Revisions From MA08.168:
04/02/2025
This policy has been reissued in accordance with the Company's annual review process.
04/22/2024
The following new policy has been developed to communicate the Company's coverage criteria for Elranatamab-bcmm (Elrexfio™).
