Linvoseltamab-gcpt (Lynozyfic)

Number: 1089

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 linvoseltamab-gcpt (Lynozyfic) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of linvoseltamab-gcpt (Lynozyfic) is required of all Aetna participating providers and members in applicable plan designs. For precertification of linvoseltamab-gcpt (Lynozyfic), 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 linvoseltamab-gcpt (Lynozyfic) medically necessary for treatment of relapsed or refractory multiple myeloma when the member has received at least 4 prior therapies, including at least one drug from each of the following categories:

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

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

2. Continuation of Therapy

   Aetna considers continuation of linvoseltamab-gcpt (Lynozyfic) 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

Linvoseltamab-gcpt is supplied as Lynozyfic 5 mg/2.5 mL (2 mg/mL) and 200 mg/10 mL (20 mg/mL) single-dose vials for administration only as an intravenous infusion.

• Premedicate to reduce the risk of cytokine release syndrome (CRS) and infusion-related reactions (IRR).
• Administer Lynozyfic as an intravenous infusion according to the step-up schedule to reduce the incidence and severity of CRS.
• The recommended dosage is as follows:

Table: Lynozyfic Dosing Schedule

Dosing Schedule	Day	Dose of Lynozyfic
Step-Up Dosing Schedule	Day 1	Step-up dose 1	5 mg
	Day 8	Step-up dose 2	25 mg
	Day 15	First treatment dose	200 mg
Weekly Dosing Schedule	Once a week after Day 15 treatment dose and once weekly from Week 4 to Week 13 for 10 treatment doses	Second and subsequent treatment doses	200 mg
Biweekly (Every 2 Weeks) Dosing Schedule	Week 14 and every 2 weeks thereafter	Subsequent treatment doses	200 mg
Patients who have achieved and maintained very good partial response (VGPR) or better at or after Week 24 and received at least 17 doses of 200 mg
Every 4 Weeks Dosing Schedule	At Week 24 or after every 4 weeks thereafter	Subsequent treatment doses	200 mg

• Lynozyfic should be administered by a healthcare provided with immediate access to emergency equipment and appropriate medical support to manage severe reactions such as cytokine release syndrome (CRS), infusion-related reactions (IRR), and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS).
• Persons should be hospitalized for 24 hours after administration of the first step-up dose and for 24 hours after administration of the second step-up dose.
• See full prescribing information for instructions on preparation and administration.

Source: Regeneron Pharmaceuticals, 2025

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
96413 - 96415	Chemotherapy administration
HCPCS codes covered if selection criteria are met:
J9601	Injection, linvoseltamab-gcpt, 1 mg
Other HCPCS codes related to the CPB:
Ixazomib, lenalidomide, pomalidomide, thalidomide –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
J9051	Injection, bortezomib (maia), not therapeutically equivalent to j9041, 0.1 mg
J9054	Injection, bortezomib (boruzu), 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 

• Lynozyfic is indicated for the treatment 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.

Linvoseltamab-gcpt is available as Lynozyfic (Regeneron Pharmaceuticals Inc.), a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager. It is a recombinant human immunoglobulin (Ig)G4 antibody which is produced by recombinant DNA technology in Chinese hamster ovary (CHO) cell suspension culture. Lynozyfic binds to the CD3 receptor expressed on the surface of T-cells and B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells. In vitro, Lynozyfic activated T-cells resulted in the release of various proinflammatory cytokines, and the lysis of multiple myeloma cells. Lynozyfic demonstrated anti-tumor activity in mouse models of multiple myeloma (Regeneron Pharmaceuticals, 2025).

According to the prescribing information, Lynozyfic carries the following boxed warnings:

• Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving Lynozyfic. Begin treatment with Lynozyfic step-up dosing to reduce the risk of of CRS. Manage CRS, withhold Lynozyfic until CRS resolves and modify the next dose or permanently discontinue based on severity.
• Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), including serious or life-threatening reactions, can occur in patients receiving Lynozyfic. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS during treatment. Manage neurologic toxicity, including ICANS, withhold Lynozyfic until neurologic toxicity, including ICANS resolves and modify the next dose or permanently discontinue based on severity.

Additionally, Lynozyfic carries the following warnings and precautions and adverse reactions:

• Warnings and precautions

  • Infections: Can cause serious or fatal infections. Monitor patients for signs or symptoms of infections and treat accordingly.
  • Neutropenia: Monitor complete blood cell counts at baseline and periodically during treatment.
  • Hepatotoxicity: Can cause hepatotoxicity. 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.
    
    

• Adverse reactions

  • The most common adverse reactions (≥20%) are musculoskeletal pain, cytokine release syndrome, cough, upper respiratory tract infection, diarrhea, fatigue, pneumonia, nausea, headache, and dyspnea.
  • The most common Grade 3 or 4 laboratory abnormalities (≥30%) are decreased lymphocyte count, decreased neutrophil count, decreased hemoglobin, and decreased white blood cell count.

On July 2, 2025, the U.S. Food and Drug Administration (FDA) granted accelerated approval to linvoseltamab-gcpt (Lynozyfic), a bispecific B-cell maturation antigen (BCMA)-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 (PI), an immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody. The FDA approval was based on supporting data from the LINKER-MM1 study (FDA, 2025).

In the LINKER-MM1 study, an open-label, multi-center, multi-cohort trial, investigators evaluated the efficacy of linvoseltamab-gcpt (Lynozyfic) in patients with relapsed or refractory multiple myeloma. The study included patients who had previously received at least 3 prior therapies, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and an anti-CD38 antibody (FDA, 2025; Regeneron Pharmaceuticals, 2025). 

The study excluded patients with prior BCMA-directed bispecific antibody therapy, prior bispecific T-cell engaging therapy, or prior BCMA CAR-T cell therapy (FDA, 2025; Regeneron Pharmaceuticals, 2025).

Patients received an intravenous infusion of Lynozyfic as a step-up dose of 5 mg on Day 1, 25 on Day 8, and the first treatment dose of 200 mg on Day 15. Then, patients received Lynozyfic 200 mg weekly from Week 4 to Week 13, followed by 200 mg every other week thereafter. After at least 24 weeks, the Phase 2 patients with a very good partial response (VGPR) or greater received Lynozyfic 200 mg every 4 weeks. Treatment continued until disease progression or unacceptable toxicity (Regeneron Pharmaceuticals, 2025).

The efficacy population consisted of 80 patients who received at least four prior lines of therapy. Efficacy was based on objective response rate (ORR) assessed by a blinded independent review committee (IRC) using International Myeloma Working Group (IMWG) criteria.

The ORR was 70% (95% Confidence Interval [CI]: 59, 80). The median time to first response was 0.95 months (range: 0.5 to 6 months). With a median follow-up of 11.3 months among responders, the estimated duration of response (DOR) was 89% (95% CI: 77, 95) at 9 months and 72% (95% CI: 54, 84) at 12 months.

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References