Elranatamab-bcmm (Elrexfio)

Number: 1040

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses elranatamab-bcmm (Elrexfio) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of elranatamab-bcmm (Elrexfio) is required of all Aetna participating providers and members in applicable plan designs. For precertification of elranatamab-bcmm (Elrexfio), call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification. 

1. Criteria for Initial Approval

   Multiple Myeloma

   Aetna considers elranatamab-bcmm (Elrexfio) medically necessary for treatment of relapsed or refractory multiple myeloma in members who have received at least 4 prior therapies, including at least one drug from each of the following categories:

   1. Anti-CD38 monoclonal antibody (e.g., daratumumab, isatuximab); and
   2. Proteasome inhibitor (e.g., bortezomib, ixazomib, carfilzomib); and
   3. Immunomodulatory agent (e.g., lenalidomide, pomalidomide, thalidomide).

   Aetna considers all other indications as experimental, investigational, or unproven.

2. Continuation of Therapy

   Aetna considers continuation of elranatamab-bcmm (Elrexfio) therapy medically necessary in members requesting reauthorization for an indication listed in Section I when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

Dosage and Administration

Elranatamab-bcmm is supplied as Elrexfio for subcutaneous injections only in the following dosage forms and strengths for injection:

• 76 mg/1.9 mL (40 mg/mL) in a single-dose vial
• 44 mg/1.1 mL (40 mg/mL) in a single-dose vial

The recommended dosages of Elrexfio subcutaneous injection are: step-up dose 1 of 12 mg on Day 1, step-up dose 2 of 32 mg on Day 4, followed by the first treatment dose of 76 mg on Day 8, and then 76 mg weekly thereafter through week 24.

For individuals who have received at least 24 weeks of treatment with Elrexfio and have achieved a response [partial response (PR) or better] and maintained this response for at least 2 months, the dose interval should transition to an every two-week schedule.

Continue treatment with Elrexfio until disease progression or unacceptable toxicity.

Table: Elrexfio Dosing Schedule

Dosing Schedule	Day	Elrexfio Dose
Step-up dosing schedule	Day 1	Step-up dose 1	12 mg
	Day 4	Step-up dose 2	32 mg
	Day 8	First treatment dose	76 mg
Weekly dosing schedule	One week after first treatment dose and weekly thereafter through week 24	Subsequent treatment doses	76 mg
Biweekly (Every 2 Weeks) dosing scheduleFootnote1*	Week 25 and every 2 weeks thereafter	Subsequent treatment doses	76 mg

Footnote1*Responders only week 25 onward.

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.

For subcutaneous injection only.

Administer pre-treatment medications as recommended.

Refer to full prescribing information for Elrexfio for preparation and administration instructions and dosage modifications for adverse reactions.

Source: Pfizer, 2023

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
96401	Chemotherapy administration, subcutaneous or intramuscular; non-hormonal anti-neoplastic
HCPCS codes covered if selection criteria are met:
J1323	Injection, elranatamab-bcmm, 1 mg
Other HCPCS codes related to the CPB:
Lenalidomide, Pomalidomide –no specific code
J9041	Injection, bortezomib, 0.1 mg
J9046	Injection, bortezomib, (dr. reddy's), not therapeutically equivalent to j9041, 0.1 mg
J9047	Injection, carfilzomib, 1 mg
J9048	Injection, bortezomib (fresenius kabi), not therapeutically equivalent to j9041, 0.1 mg
J9049	Injection, bortezomib (hospira), not therapeutically equivalent to j9041, 0.1 mg
J9144	Injection, daratumumab, 10 mg and hyaluronidase-fihj
J9145	Injection, daratumumab, 10 mg
J9227	Injection, isatuximab-irfc, 10 mg
ICD-10 codes covered if selection criteria are met:
C90.00, C90.02	Multiple myeloma

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Background

U.S. Food and Drug Administration (FDA)-Approved Indications 

• Elrexfio is indicated for the treatment of adult patients 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.

Elranatamab-bcmm is available as Elrexfio (Pfizer, Inc.) and is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager. Elrexfio binds BCMA on plasma cells, plasmablasts, and multiple myeloma cells and CD3 on T-cells leading to cytolysis of the BCMA-expressing cells. The Elrexfio activated T-cells produced proinflammatory cytokine release with resultant multiple myeloma cell lysis (Pfizer, 2023).

According to the prescribing instructions, Elrexfio carries the following black box warnings and restriction:

• Cytokine Release Syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving Elrexfio. Initiate treatment with Elrexfio step-up dosing schedule to reduce risk of CRS. Withhold Elrexfio until CRS resolves or permanently discontinue based on severity.
• Neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), and serious and life-threatening reactions, can occur in patients receiving Elrexfio. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS, during treatment. Withhold Elrexfio until the neurologic toxicity resolves or permanently discontinue based on severity.
• Elrexfio is available only through a restricted program called the Elrexfio Risk Evaluation and Mitigation Strategy (REMS).

Per the prescribing information, Elrexfio carries the following warnings and precautions:

• Infections: Can cause severe, life-threatening, or fatal infections. Monitor patients for signs and symptoms of infection and treat appropriately. Do not initiate treatment in patients with active infections.
• Neutropenia: Monitor complete blood cell counts at baseline and periodically during treatment.
• Hepatotoxicity: Can cause elevated ALT, AST, and bilirubin. Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated.
• Embryo-fetal toxicity: May cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception.

Per the prescribing information, Elrexfio carries the following adverse reactions:

• Most common adverse reactions (≥ 20%): Cytokine release syndrome, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and pyrexia.
• Most common Grade 3 to 4 laboratory abnormalities (≥ 30%): Decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets.

On August 14, 2023, the U.S. Food and Drug Administration (FDA) granted accelerated approval to elranatamab-bcmm (Elrexfio), a bispecific B-cell maturation antigen (BMCA)-directed CD3 T-cell engager, 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. The FDA approval was based on supporting data from the phase 2 MagnetisMM-3 trial (FDA, 2023).

In the MagnetisMM-3 study, an open-label, single-arm, multi-center, phase 2 trial, investigators evaluated the efficacy of Elrexfio monotherapy in patients with relapsed or refractory multiple myeloma. The trial included patients who were refractory to at least one proteasome inhibitor (PI), one immunomodulatory agent (IMiD), and one anti-CD38 monoclonal antibody. MagnetisMM-3 included 123 patients naive to prior BCMA-directed therapy (pivotal Cohort A) and 64 patients with prior BCMA-directed antibody drug conjugate (ADC) or chimeric antigen receptor (CAR) T-cell therapy (supportive Cohort B). AT study enrollment, patients had measurable disease by International Myeloma Working Group (IMWG) criteria. Patients received subcutaneous administration of Elrexfio at step-up doses of 12 mg on Day 1 and 32 mg on Day 4 of treatment, followed by the first treatment dose of Elrexfio (76 mg) on Day 8 of treatment. Subsequently, patients received 76 mg once weekly. After 24 weeks, in patients who achieved an IMWG response category of partial response or better with responses lasting for at least 12 months, the dose interval was adjusted from every week to every 2 weeks. The primary efficacy population was comprised of 97 patients naive to prior BCMA-directed therapy and who previously received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The primary efficacy outcomes were objective response rate (ORR) and duration of response (DOR), as assessed by blinded independent central review (BICR) based on IMWG criteria. The efficacy results for the 97 evaluable patients included: ORR of 57.7% (95% confidence interval [CI]: 47.3%, 67.7%), median follow-up of 11.1 months among responders, median DOR was not reached (95% CI: 12 months, not reached), and DOR rate at 6 months was 90.4% (95% CI: 78.4%, 95.9%) and at 9 months was 82.3% (95% CI: 67.1%, 90.9%) (FDA, 2023; Pfizer, 2023).

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References