CurrentBlue Cross Blue Shield - TennesseePolicy N/A

Denosumab Products (Xgeva® and biosimilars) — Coverage Criteria

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Governs medical policy coverage, authorization durations, and dosing limits for denosumab products for oncology-related indications for Blue Cross Blue Shield - Tennessee members.

Policy Summary

PayerBlue Cross Blue Shield - Tennessee

PolicyDenosumab Products (Xgeva® and biosimilars) — Coverage Criteria

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateN/A

Last ReviewJun 30, 2026

Next Review DateJun 30, 2026

Key ActionObtain prior authorization with indication-specific durations (typically 12 months; 2 months for hypercalcemia of malignancy) and document clinical benefit for reauthorization.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

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CurrentBlue Cross Blue Shield - TennesseePolicy N/A

Denosumab Products (Xgeva® and biosimilars) — Coverage Criteria

Customize your policy alerts

Sign up for all blue cross blue shield - tennessee policy alerts

Know when blue cross blue shield - tennessee releases new policies or updates existing guidance.

Monitor payer policy activity

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Governs medical policy coverage, authorization durations, and dosing limits for denosumab products for oncology-related indications for Blue Cross Blue Shield - Tennessee members.

Policy Summary

PayerBlue Cross Blue Shield - Tennessee

PolicyDenosumab Products (Xgeva® and biosimilars) — Coverage Criteria

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateN/A

Last ReviewJun 30, 2026

Next Review DateJun 30, 2026

Key ActionObtain prior authorization with indication-specific durations (typically 12 months; 2 months for hypercalcemia of malignancy) and document clinical benefit for reauthorization.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

120 mgCommon oncologic dose

q4wSchedule (oncologic)

60 mg q6moDose for systemic mastocytosis

12 moTypical auth period

2 moHypercalcemia auth

CrCl <35Renal threshold

Coverage Criteria for Denosumab Products

Multiple Myeloma

Covered when ALL of the following are met for multiple myeloma:

Multiple Myeloma - prevention of skeletal-related events: Member has multiple myeloma and therapy is for prevention of skeletal-related events.authorization = 12 months

See dosing: 120 mg on days 1, 8, and 15 of the first month then 120 mg every 4 weeks for ongoing prevention of SREs.

Bone Metastases from Solid Tumor

Covered when ALL of the following are met for bone metastases from solid tumors:

Bone metastases from solid tumor - prevention or palliative care: Member has bone metastases from a solid tumor (e.g., breast, non-small cell lung, thyroid, kidney, prostate) OR the request is for palliative care for bone metastases from thyroid carcinoma.authorization = 12 months

Dose typically 120 mg on days 1, 8, and 15 of the first month then 120 mg every 4 weeks.

Giant Cell Tumor of Bone

Covered when ALL of the following are met for giant cell tumor of bone:

Giant cell tumor of bone - unresectable or surgery likely to result in severe morbidity: Member has giant cell tumor of bone that is unresectable or surgical resection is likely to result in severe morbidity.authorization = 12 months

Loading regimen: 120 mg subcutaneously on days 1, 8, and 15 of the first month, then 120 mg every 4 weeks.

Hypercalcemia of Malignancy

Covered when ALL of the following are met for hypercalcemia of malignancy:

Hypercalcemia of malignancy that is refractory to IV bisphosphonate therapy OR there is a documented clinical reason to avoid IV bisphosphonates (see Appendix).authorization = 2 months (reauthorization allowed if benefit demonstrated by disease stability or improvement)

Loading regimen: 120 mg subcutaneously on days 1, 8, and 15 of the first month, then 120 mg every 4 weeks.

Systemic Mastocytosis (Compendial Use)

Covered compendial uses and step therapy:

Systemic mastocytosis - osteopenia/osteoporosis (compendial use): Second-line therapy after an adequate trial of bisphosphonate therapy OR when the member is not a candidate for bisphosphonates (e.g., renal insufficiency).authorization = 12 months

Dose for osteopenia/osteoporosis in systemic mastocytosis: 60 mg subcutaneously every 6 months.

Indication-specific dosing coverage

Coverage and typical dosing by indication as listed in policy

Giant Cell Tumor of Bone: Denosumab covered with subcutaneous 120 mg on days 1, 8, and 15 of the first month, then 120 mg every 4 weeks.

See medication quantity limits and product-specific dosing (Xbryk, Xtrenbo listings).

Hypercalcemia of Malignancy: Denosumab covered with subcutaneous 120 mg on days 1, 8, and 15 of the first month, then 120 mg every 4 weeks.

Product-specific dosing reflected in medication quantity limits.

Osteopenia or Osteoporosis in Systemic Mastocytosis: Denosumab covered with subcutaneous 60 mg every 6 months for systemic mastocytosis-related osteopenia/osteoporosis.

Per compendial use and medication quantity limits.

Palliative Care for Bone Metastases from Thyroid Carcinoma:

Indications not specifically listed in this policy (other than the FDA-approved indications and the compendial uses enumerated here) are considered experimental/investigational and not medically necessary. Requests for denosumab for unlisted indications are subject to denial.

Clinical reasons that may justify avoiding intravenous bisphosphonate therapy — and therefore support use of an alternative such as denosumab — include: renal insufficiency with creatinine clearance < 35 mL/min, a documented history of intolerance to an IV bisphosphonate, or acute renal impairment. These criteria are listed in the policy appendix as circumstances in which IV bisphosphonates may be inappropriate.

All indications that are not explicitly listed in the FDA-approved indications or the compendial uses section of this policy are considered not medically necessary (experimental/investigational) and are not covered.

Per Tennessee statute, off-label uses of FDA-approved drugs (including denosumab) must be recognized in a statutorily recognized compendium or supported by published peer-reviewed medical literature to be eligible for coverage. Off-label denosumab uses that lack such compendial or peer-reviewed support may be denied under state rules.

Covered Dosing Regimens

Indication	Dosing regimen	Coverage status
Giant cell tumor of bone (unresectable or surgery likely to cause severe morbidity)
120 mg subcutaneously on days 1, 8, and 15 of the first month, then 120 mg every 4 weeks
covered

Indication	Dosing regimen	Coverage status
Osteopenia or osteoporosis in patients with systemic mastocytosis (compendial use; second-line after bisphosphonates or if bisphosphonates contraindicated)
60 mg subcutaneously every 6 months
covered

Dosing regimens — quick reference

Oncologic loading and maintenance120 mg subcutaneously on days 1, 8, and 15 of the first month, then 120 mg every 4 weeks (common for prevention of SREs, bone metastases palliative care, giant cell tumor, and hypercalcemia of malignancy)

Multiple myeloma / bone metastases maintenance120 mg subcutaneously every 4 weeks

Giant cell tumor of bone regimenLoading: 120 mg on days 1, 8, 15; then 120 mg every 4 weeks

Systemic mastocytosis (osteopenia/osteoporosis)60 mg subcutaneously every 6 months

Palliative care for thyroid carcinoma bone metastases120 mg subcutaneously every 4 weeks

Product and Policy Coding

Covered ProductsNDC | mixedCovered

Denosumab (Xgeva, biosimilars listed)

Product list: Denosumab (Xgeva®); Denosumab-kyqq (Aukelso™); Denosumab-nxxp (Bilprevda®); Denosumab-bnht (Bomyntra®); Denosumab-bmwo (Osenvelt®); Denosumab-bbdz (Wyost®); Denosumab-dssb (Xbryk™); Denosumab-qbde (Xtrenbo™)

Policy identifiers / referencesmixed

ID_CHS_2024d

Policy effective/identifier

SREs — definition and coding context

Definition (concise)Skeletal-related events (SREs) are bone complications related to metastatic bone disease — commonly pathologic fracture, spinal cord compression, or need for radiation or surgery to bone.

Clinical contextPrevention of SREs is an approved indication for denosumab in patients with multiple myeloma and bone metastases from solid tumors

Coding/context noteSRE prevention dosing typically follows 120 mg subcutaneously every 4 weeks as listed in medication quantity limits

Prior Authorization, Step Therapy, and Provider Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for denosumab and related products. Authorization durations vary by indication (for example, 12 months for prevention of skeletal-related events or multiple myeloma; 2 months for hypercalcemia of malignancy). Reauthorization for continued treatment may be granted for 12 months when the member is experiencing clinical benefit demonstrated by disease stability or improvement. Providers should include documentation supporting the indicated diagnosis, prior therapies (when applicable), and clinical rationale for duration requested.

Prior authorization required for all indications
Typical initial authorization lengths: 12 months (most indications), 2 months (hypercalcemia of malignancy)
Reauthorization: 12 months for members demonstrating benefit (disease stability or improvement)

Documentation Required

Off‑Label Use Requirements

Background and Definitions

Denosumab is indicated for the prevention of skeletal-related events (SREs) in patients with multiple myeloma and in patients with bone metastases from solid tumors, and for the treatment of hypercalcemia of malignancy that is refractory to IV bisphosphonates. It is also indicated for treatment of unresectable or morbid giant cell tumor of bone. Recognized compendial uses include second-line therapy for osteopenia or osteoporosis in systemic mastocytosis and use as palliative therapy for bone metastases from thyroid cancer. Other uses are considered investigational.

Definitions — Skeletal-related events

Pathologic fractureFracture of bone due to tumor involvement rather than trauma — listed as a skeletal-related event (SRE)

Spinal cord compressionCompression of the spinal cord from tumor in bone causing neurologic compromise — included among SREs

Need for radiation or surgery to boneProcedures such as radiation therapy or surgical intervention to bone for disease control or symptom relief are considered SREs

SREs — prevention (summary)

Position in Therapy

second-line

Systemic mastocytosis - line of therapy: Denosumab is considered second-line therapy for osteopenia/osteoporosis in systemic mastocytosis after bisphosphonate therapy or when bisphosphonates are contraindicated or not tolerated (e.g., renal insufficiency).

Policy Revision History

2026-06-30policy effective / approvedLatest

Medical Policy Manual approved revision; do not implement until 6/30/26 (policy identifier ID_CHS_2024d referenced).

2025-05reference update

Xgeva (Denosumab) package insert listed with date May 2025 in references.

Policy Summary

PayerBlue Cross Blue Shield - Tennessee

PolicyDenosumab Products (Xgeva® and biosimilars) — Coverage Criteria

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateN/A

Last ReviewJun 30, 2026

Next Review DateJun 30, 2026

Key ActionObtain prior authorization with indication-specific durations (typically 12 months; 2 months for hypercalcemia of malignancy) and document clinical benefit for reauthorization.

SourceLink

On This Page

Denosumab covered with subcutaneous 120 mg every 4 weeks for palliative management of thyroid cancer bone metastases.

Per medication quantity limits.

Prevention of Skeletal-Related Events in Patients with Bone Metastases from Solid Tumors or Multiple Myeloma: Denosumab covered with subcutaneous 120 mg every 4 weeks for prevention of skeletal-related events.

Standard oncologic dosing per policy medication quantity limits.

Creatinine clearance threshold

Creatinine clearance thresholdAvoid IV bisphosphonate therapy when creatinine clearance < 35 mL/min

Clinical implicationRenal insufficiency (CrCl < 35 mL/min) listed as a reason to avoid IV bisphosphonates and consider alternatives such as denosumab

Other listed reasonsHistory of intolerance to IV bisphosphonate; acute renal impairment

Coverage follows FDA-approved labeled indications and off‑label uses only when supported by a statutorily recognized compendium or peer‑reviewed medical literature in accordance with Tennessee statute. Providers requesting coverage for off‑label use must document the compendial or peer‑reviewed citation that supports the requested indication and include clinical rationale and prior treatment history as applicable.

Off‑label uses require recognition in a statutorily recognized compendium or published peer‑reviewed literature
Include supporting compendium citation (e.g., NCCN, Drugdex, AHFS) or peer‑reviewed reference with the prior authorization request
Document clinical rationale and prior therapies tried/failed

Denial Risk

Unlisted Indications

Use for indications not listed in the policy (unlisted indications) is considered experimental/investigational and not medically necessary unless there is compelling compendial or peer‑reviewed evidence meeting the off‑label requirements above. Requests for unlisted indications should include the supporting literature and will be reviewed on a case‑by‑case basis; absent qualifying evidence, these requests will be denied as not medically necessary.

Unlisted indications are generally not covered and are considered experimental/investigational
To be considered, submit peer‑reviewed literature or compendial support meeting statutory requirements

Note

Provider Reference Guidance

Providers should reference standard clinical compendia for regimen, dosing, contraindications, precautions, and monitoring information when preparing prior authorization requests or when making treatment decisions.

Refer to NCCN, Drugdex (Micromedex), or AHFS for dosing, contraindications, and monitoring
Include compendial regimen/dose details in the prior authorization when applicable

Step Therapy

Step Therapy for Systemic Mastocytosis

Step therapy: for systemic mastocytosis-related osteopenia/osteoporosis, denosumab is considered second‑line after an adequate trial of bisphosphonate therapy. Denosumab may be authorized when there is documented intolerance, contraindication, or renal insufficiency (see Appendix) to IV bisphosphonates.

Denosumab is second‑line for osteopenia/osteoporosis in systemic mastocytosis after bisphosphonate trial
Authorization may be granted if bisphosphonates are contraindicated, not tolerated, or in renal insufficiency

SREs (short definition)Prevention of skeletal-related events (SREs): interventions to avoid pathologic fracture, spinal cord compression, or need for radiation/surgery to bone.

Indications tied to SRE preventionDenosumab indicated for prevention of SREs in multiple myeloma and in patients with bone metastases from solid tumors

Common prevention regimenTypically 120 mg subcutaneously every 4 weeks for SRE prevention per product listings