Talquetamab-tgvs (Talvey)

Number: 1042

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 talquetamab-tgvs (Talvey) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of talquetamab-tgvs (Talvey) is required of all Aetna participating providers and members in applicable plan designs. For precertification of talquetamab-tgvs (Talvey), 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

   Aetna considers talquetamab-tgvs (Talvey) medically necessary for treatment of the following indications:

   1. Multiple myeloma - for treatment of relapsed or refractory multiple myeloma when any of the following criteria is met:

      1. The requested medication will be used as a bridge to B-cell associated maturation antigen-directed (BCMA) chimeric antigen receptor (CAR) T-cell therapy (e.g., idecabtagene vicleucel (Abecma), ciltacabtagene autoleucel (Carvykti)) and member has received prior treatment with at least one line of therapy, including at least one drug from each of the following categories:

         1. Immunomodulatory agent (e.g., lenalidomide, pomalidomide, thalidomide); and
         2. Proteasome inhibitor (e.g., bortezomib, ixazomib, carfilzomib); or

      2. The requested medication will be used as a single agent and 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); or
            

      3. The requested medication will be used in combination with teclistamab-cqyv (Tecvayli) and member has received at least 3 prior therapies; or

   2. POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes) Syndrome, Monoclonal Immunoglobulin Deposition Disease (MIDD), and Monoclonal Gammopathy of Renal Significance (MGRS) - for treatment of POEMS syndrome, MIDD, and plasma cell-related MGRS as a single agent or in combination with teclistamab-cqyv (Tecvayli).

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

2. Continuation of Therapy

   Aetna considers continuation of talquetamab-tgvs (Talvey) therapy medically necessary in members requesting reauthorization for an indication listed in the Criteria for Initial Approval section when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

Dosage and Administration

Talquetamab-tgvs is supplied as Talvey injection:

• 3 mg/1.5 mL (2 mg/mL) in a single-dose vial
• 40 mg/mL in a single-dose vial 

Talvey is for subcutaneous injection and should only be administered by a qualified healthcare professional.

Individuals should be hospitalized for 48 hours after all doses within the step-up dosing schedule.

Administer pretreatment medications as recommended.

Table: Talvey Weekly Dosing Schedule

Dosing Schedule	Day	DoseFootnote1*
Step-up dosing schedule	1	Step-up dose 1	0.01 mg/kg
	4Footnote2**	Step-up dose 2	0.06 mg/kg
	5Footnote2**	First treatment dose	0.4 mg/kg
Weekly dosing schedule	One week after first treatment dose and weekly thereafterFootnote3***	Subsequent treatment doses	0.4 mg/kg once weekly

Footnote1* Based on actual body weight

Footnote2** Dose may be administered between 2 to 4 days after the previous dose and may be given up to 7 days after the previous dose to allow for resolution of adverse reactions.

Footnote3*** Maintain a minimum of 6 days between weekly doses. 

Table: Talvey Biweekly (Every 2 Weeks) Dosing Schedule

Dosing Schedule	Day	DoseFootnote4†
Step-up dosing schedule	1	Step-up dose 1	0.01 mg/kg
	4Footnote5††	Step-up dose 2	0.06 mg/kg
	7Footnote5††	Step-up dose 3	0.4 mg/kg
	10Footnote6†††	First treatment dose	0.8 mg/kg
Biweekly (every 2 weeks) dosing schedule	Two weeks after first treatment dose and every 2 weeks thereafterFootnote7‡	Subsequent treatment doses	0.8 mg/kg every 2 weeks

Footnote4^† Based on actual body weight

Footnote5^†† Dose may be administered between 2 to 4 days after the previous dose and may be given up to 7 days after the previous dose to allow for resolution of adverse reactions.

Footnote6^††† Dose may be administered between 2 to 7 days after step-up dose 3.

Footnote7^‡ Maintain a minimum of 12 days between biweekly (every 2 weeks) doses. 

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

Source: Janssen Biotech, 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:
J3055	Injection, talquetamab-tgvs, 0.25 mg
Other HCPCS codes related to the CPB:
Lenalidomide, Pomalidomide, Thalidomide, Ixazomib –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
J9380	Teclistamab-cqyv, 0.5 mg
Q2055	Idecabtagene vicleucel, up to 510 million autologous b-cell maturation antigen (bcma) directed car-positive t cells, including leukapheresis and dose preparation procedures, per therapeutic dose
Q2056	Ciltacabtagene autoleucel, up to 100 million autologous b-cell maturation antigen (bcma) directed car-positive t cells, including leukapheresis and dose preparation procedures, per therapeutic dose
ICD-10 codes covered if selection criteria are met:
C90.00, C90.02	Multiple myeloma
D47.2	Monoclonal gammopathy [POEMS] [renal significance (MGRS)]
D47.Z9	Other specified neoplasms of uncertain behavior of lymphoid, hematopoietic and related tissue [Plasma Cell-related Monoclonal Immunoglobulin Deposition Disease (MIDD)]

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Background

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

• 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

Compendial Uses

• Multiple myeloma
• POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome
• Monoclonal immunoglobulin deposition disease (MIDD)
• Plasma cell-related monoclonal gammopathy of renal significance (MGRS)

Talquetamab-tgvs is available as Talvey (Janssen Biotech, Inc.) and is a bispecific G protein-coupled receptor class C group 5 member D (GPRC5D)-directed CD3 T-cell engaging antibody. Talvey binds to the CD3 receptor on the surface of T-cells and GPRC5D expressed on the surface of multiple myeloma cells and non-malignant plasma cells in addition to healthy tissues, for example, epithelial cells in keratinized tissues of the skin and tongue. The activation of T-cells by Talvey in vitro has shown the release of proinflammatory cytokines and resulted in the lysis of multiple myeloma cells. Talvey displayed anti-tumor activity in mouse models of multiple myeloma (Janssen Biotech, 2023).

According to the prescribing information, Talvey carries the following black box warnings and restriction:

• Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving Talvey. Initiate Talvey treatment with step-up dosing to reduce the risk of CRS. Withhold Talvey until CRS resolves or permanently discontinue based on severity.
• Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), can occur in patients receiving Talvey. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment. Withhold or permanently discontinue Talvey based on severity.
• Talvey is available only through a restricted program called the Tecvayli and Talvey Risk Evaluation and Mitigation Strategy (REMS).

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

• Oral toxicity and weight loss: Monitor for oral toxicity and weight loss. Withhold or permanently discontinue based on severity.
• Infections: Can cause serious, life-threatening, or fatal infections. Monitor for signs and symptoms of infection; treat appropriately. Withhold or consider permanent discontinuation based on severity.
• Cytopenias: Monitor complete blood counts.
• Skin toxicity: Monitor for skin toxicity, including rash progression, for early intervention and treat appropriately. Withhold as recommended based on severity.
• Hepatotoxicity: Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold or consider permanent discontinuation based on severity.
• 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, Talvey carries the following adverse reactions:

• The most common adverse reactions (≥ 20%) include: Pyrexia, CRS, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, weight decreased, dry mouth, xerosis, dysphagia, upper respiratory tract infection, diarrhea, hypotension, and headache.
• The most common Grade 3 or 4 laboratory abnormalities (≥ 30%) include: lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, and hemoglobin decreased.

On August 9, 2023, the U.S. Food and Drug Administration granted accelerated approval to talquetamab-tgvs (Talvey) 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 MMY1001 (MonumenTAL-1) trial (FDA, 2023).

In the MMY1001 (MonumenTAL-1) trial, a single-arm, open-label, multicenter study, investigators evaluated the efficacy of Talvey monotherapy in patients with relapsed or refractory multiple myeloma. The study included patients who previously received at least three prior systemic therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Patients treated with the weekly dosing schedule received step-up doses of 0.01 mg/kg and 0.06 mg/kg of Talvey followed by Talvey 0.4 mg/kg subcutaneously weekly thereafter. Patients treated with biweekly (every 2 weeks) dosing schedule received step-up doses of 0.01 mg/kg, 0.06 mg/kg, and 0.3 mg/kg (0.75 times the recommended step-up dose 3) of Talvey followed by Talvey 0.8 mg/kg subcutaneously biweekly, thereafter. Treatment continued until disease progression or unacceptable toxicity for patients on either dosing schedules. The primary efficacy outcome measures included overall response rate (ORR) and duration of response (DOR) as assessed by an Independent Review Committee using International Myeloma Working Group (IMWG) criteria. The primary efficacy population included 187 patients who had previously received at least 4 prior lines of therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The ORR in the 100 patients receiving Talvey 0.4 mg/kg weekly was 73% (95% confidence interval [CI]: 63.2%, 81.4%) and median DOR was 9.5 months (95% CI: 6.5, not estimable). The ORR in the 87 patients receiving 0.8 mg/kg biweekly was 73.6% (95% CI: 63%, 82.4%) and median DOR was not estimable; an estimated 85% or responders maintained response for at least 9 months (Janssen, 2023; FDA, 2023).

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References