CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Elrexfio (elranatamab-bcmm)

Defines accepted indications, exclusion criteria, warnings/REMS, and coding for Elrexfio (elranatamab-bcmm) for treatment of cancer (multiple myeloma) and outlines evidence sources required for authorization and continuation rules.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyElrexfio (elranatamab-bcmm)

Policy CodePolicy N/A

Change TypeAdministrative/template updatesclarifying edits

Effective Date

Next Review Date

Key ActionAuthorize only when use is supported by FDA labeling, CMS-recognized compendia, NCCN/ASCO guidelines, or acceptable peer-reviewed literature meeting CMS Medicare Benefit Policy Manual Chapter 15 requirements.

SourceLink

POLICY UPDATE CHANGES

Converted to new Evolent guideline template and replaced prior UM ONC_1482 Elrexfio guideline.

Added specific drug names to drug classes in indication section.

1Approved Indication (Multiple myeloma)

J1323HCPCS J-code listed

76Single dose limit (mg)

REMSREMS required

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Coverage Summary

Coverage stance: covered_with_criteria; Approved Indication: Approved Indication (Multiple myeloma). Scope: Defines accepted indications, exclusion criteria, warnings/REMS, and coding for Elrexfio (elranatamab-bcmm) for treatment of cancer (multiple myeloma) and outlines evidence sources required for authorization and continuation rules. Elrexfio (elranatamab-bcmm) is indicated for adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Authorization requires evidence per CMS Medicare Benefit Policy Manual Chapter 15 (FDA labeling, CMS compendia, NCCN/ASCO guidelines, or acceptable peer-reviewed literature).

Initial Authorization Criteria

Initial Authorization — Multiple Myeloma

Covered when ALL of the following are met:

ALL of the following

Member is an adult with relapsed or refractory multiple myeloma
Member has received at least four prior lines of therapy
Includes ALL of the following drug classes
- Prior therapy includes a proteasome inhibitor (e.g., bortezomib, carfilzomib, ixazomib)
- Prior therapy includes an immunomodulatory agent (e.g., lenalidomide, thalidomide, pomalidomide)
- Prior therapy includes an anti-CD38 monoclonal antibody (e.g., daratumumab, isatuximab)

Use is supported by FDA labeling, CMS-recognized compendia, NCCN, ASCO guidelines, or acceptable peer-reviewed literature meeting CMS Medicare Benefit Policy Manual Chapter 15 requirements

Continuation Authorization Criteria

Continuation Authorization (Exemption rule)

Continuation requests for a not-approvable medication shall be exempt from this Evolent policy provided ALL of the following are met:

ALL of the following

The member has not experienced disease progression on the requested medication
The requested medication was used within the last year without a lapse of more than 30 days of having an active authorization
Additional medication(s) are not being added to the continuation request

Prior Authorization

Exclusion Criteria / Not Medically Necessary

Not covered when ANY of the following exclusion conditions are present:

ANY of the following

Disease progression while taking Elrexfio (elranatamab-bcmm)
Concurrent use with other anticancer therapies
Dosing exceeds single dose limit of Elrexfio (elranatamab-bcmm) 76 mg
Sufficient evidence is defined by consideration of ALL of the following
- Whether the clinical characteristics of the patient and the cancer are adequately represented in the published evidence

Safety and REMS Requirements

Safety/REMS Requirements

Treatment is subject to boxed warnings and REMS program requirements:

ALL of the following

Risk of Cytokine Release Syndrome (CRS); initiate treatment with step-up dosing schedule; withhold or discontinue based on severity
Risk of neurologic toxicity including ICANS; monitor and withhold or discontinue based on severity
Elrexfio is available only through ELREXFIO REMS

Documentation Required

REMS and safety monitoring

Applicable Codes

Drug HCPCS (J-code)HCPCSCovered

J1323

Injection, elranatamab-bcmm, 1 mg

Thresholds / Administrative Quick Reference

Single dose limit76 mg

REMS requirementElrexfio is available only through ELREXFIO REMS; REMS required due to risk of CRS and neurologic toxicity

Billing code (example)J1323 - Injection, elranatamab-bcmm, 1 mg

Use restrictionDosing exceeding single dose limit (76 mg) is an exclusion for coverage

Administrative noteAuthorize only when supported by FDA labeling, CMS compendia, NCCN/ASCO guidelines, or acceptable peer-reviewed literature per CMS Chapter 15

Provider Actions & Documentation Requirements

Prior Authorization

Authorization evidence requirement

Authorization requires that use is supported by one of the following: FDA approved product labeling, CMS-recognized compendia, NCCN or ASCO clinical guidelines, or peer-reviewed literature that meets CMS Medicare Benefit Policy Manual Chapter 15 requirements. Reference HCPCS: J1323.

FDA approved product labeling
CMS-recognized compendia
NCCN or ASCO clinical guidelines
Peer-reviewed literature meeting CMS Medicare Benefit Policy Manual Chapter 15

Documentation Required

Prior therapy documentation

Document that the member has received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Examples of agents in each class are provided in the policy (e.g., bortezomib, carfilzomib, ixazomib; lenalidomide, thalidomide, pomalidomide; daratumumab, isatuximab). Reference HCPCS: J1323.

At least four prior lines of therapy
Prior proteasome inhibitor (e.g., bortezomib, carfilzomib, ixazomib)

Clinical Evidence

Key evidence supporting this policy includes the MagnetisMM-3 phase 2 trial (Nat Med 2023) and the Elrexfio prescribing information, Pfizer Inc. 2025. Per policy, FDA labeling is a required evidence source for authorization decisions under the CMS Medicare Benefit Policy Manual Chapter 15.

Clinical Outcome Definition

Clinically meaningful outcomesASCO definitions: hazard ratio < 0.80 and OS/PFS benefit ≥ 3 months

Background

Background: Elrexfio (elranatamab-bcmm) is indicated for relapsed or refractory multiple myeloma in adults meeting prior therapy requirements. Major safety risks include cytokine release syndrome (CRS) and neurologic toxicity, including ICANS; because of these risks Elrexfio is available only through the ELREXFIO REMS program.

Revision History

2025-09administrativeLatest

Converted to new Evolent guideline template; replaced prior UM ONC_1482 Elrexfio guideline and updated references.

2024-09content_update

Added specific drug names to drug classes in the indication section (examples: bortezomib, carfilzomib, ixazomib; lenalidomide, thalidomide, pomalidomide; daratumumab, isatuximab).

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyElrexfio (elranatamab-bcmm)

Policy CodePolicy N/A

Change TypeAdministrative/template updatesclarifying edits

Effective Date

Next Review Date

SourceLink

On This Page

Continuation exemption conditions

Allow continuation requests for medications otherwise not approvable when ALL of the following are met: - The member has not experienced disease progression on the requested medication - The requested medication was used within the last year without a lapse of more than 30 days of having an active authorization - Additional medication(s) are not being added to the continuation request Reference HCPCS: J1323.

No disease progression on the requested medication
Used within the last year with ≤30-day lapse of active authorization
No additional medications added to the continuation request

Whether the administered therapy regimen is adequately represented in the published evidence

Whether reported study outcomes represent clinically meaningful outcomes (ASCO definitions: e.g., hazard ratio < 0.80; OS/PFS benefit at least 3 months)

Whether experimental design is appropriate to address the investigative question

Non-randomized trials with significant subjects may be supportive; case reports and abstracts without full article are inadequate

Investigational use with an off-label indication that lacks sufficient evidence or is not generally accepted by the medical community

Denial Risk

Exclusion triggers for denial

Deny when ANY of the following exclusion triggers are present: - Disease progression while taking Elrexfio (elranatamab-bcmm) - Concurrent use with other anticancer therapies - Dosing exceeds single dose limit of Elrexfio (elranatamab-bcmm) 76 mg - Investigational or off-label use that lacks sufficient supporting evidence per stated evidence standards Reference HCPCS: J1323.

Disease progression on Elrexfio
Concurrent anticancer therapy
Single dose > 76 mg
Off-label use lacking sufficient evidence

Ensure Elrexfio is administered only under the ELREXFIO REMS program. Initiate treatment with the recommended step-up dosing schedule to reduce CRS risk. Monitor patients for cytokine release syndrome (CRS) and neurologic toxicity including ICANS; withhold the drug until toxicity resolves or permanently discontinue based on severity. Follow REMS program requirements for safe administration and monitoring. Reference HCPCS: J1323.

Administration only through ELREXFIO REMS
Initiate step-up dosing schedule
Monitor for CRS and neurologic toxicity (ICANS)
Withhold or permanently discontinue based on severity

Prior immunomodulatory agent (e.g., lenalidomide, thalidomide, pomalidomide)

Prior anti-CD38 monoclonal antibody (e.g., daratumumab, isatuximab)

Denial Risk

Exclusion triggers for denial

Operational denial-risk summary for clinicians and billing staff: deny when ANY of the following are present — disease progression on Elrexfio, concurrent anticancer therapy, dosing that exceeds the single-dose limit of 76 mg, or investigational/off-label use lacking sufficient supporting evidence per the policy's evidence standards. Reference HCPCS: J1323.

Disease progression on Elrexfio
Concurrent anticancer therapy
Single dose > 76 mg
Off-label use lacking sufficient evidence