Medicare Advantage

Medical Policy

Title:

Belantamab mafodotin-blmf (Blenrep)

Policy #:

MA08.192

Policy

In the absence of coverage criteria from applicable Medicare statutes, regulations, NCDs, LCDs, CMS manuals, or other Medicare coverage documents, this policy uses internal coverage criteria developed by the Company in consideration of peer-reviewed medical literature, clinical practice guidelines, and/or regulatory status.

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

Belantamab mafodotin-blmf (Blenrep) is considered medically necessary and, therefore, covered for the treatment of adults with relapsed or refractory multiple myeloma (MM) when all the following criteria are met:

The individual has received at least two prior therapies, including a proteasome inhibitor and an immunomodulatory agent
In combination with bortezomib and dexamethasone (BVd) for the first eight cycles, then continued as monotherapy
The individual has Eastern Cooperative Oncology Group (ECOG) performance status of 0–2

The above regimens may also be used for the treatment of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) (useful in certain circumstances), monoclonal immunoglobulin deposition disease (MIDD), and plasma cell–related monoclonal gammopathy of renal significance (MGRS).

EXPERIMENTAL/INVESTIGATIONAL

All other uses for belantamab mafodotin-blmf (Blenrep) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the service.

Guidelines

There is no Medicare coverage determination addressing belantamab mafodotin-blmf (Blenrep); therefore, the Company policy is applicable.

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

THE EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE STATUS

The ECOG Performance Status was originally published in 1982 in the American Journal of Clinical Oncology*. ECOG states, "These scales and criteria are used by doctors and researchers to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. They are included here for health care professionals to access."

GRADE	ECOG
0	Fully active, able to carry on all pre-disease performance without restriction
1	Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
2	Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50 percent of waking hours
3	Capable of only limited self care, confined to bed or chair more than 50 percent of waking hours
4	Completely disabled. Cannot carry on any self care: Totally confined to bed or chair
5	Dead

*Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol.1982;5(6):649-655.

EXAMPLES OF PRIOR THERAPY:

Proteasome inhibitors (PI): bortezomib (Velcade®), carfilzomib (Kyprolis®), and ixazomib (Ninlaro®)

Immunomodulatory agents: lenalidomide (Revlimid®), pomalidomide (Pomalyst®), and thalidomide (Thalomid®)

BENEFIT APPLICATION

Subject to the applicable Evidence of Coverage, belantamab mafodotin-blmf (Blenrep) is covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria listed in this medical policy are met.

For Medicare Advantage members, certain drugs are available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when belantamab mafodotin-blmf (Blenrep) is covered under a member's medical benefit (Part B benefit). It does not address instances when belantamab mafodotin-blmf (Blenrep) is covered under a member’s pharmacy benefit (Part D benefit).

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Belantamab mafodotin-blmf (Blenrep) was approved by the FDA on August 5, 2020, for the treatment of adults with relapsed or refractory MM who have received at least four prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. Belantamab mafodotin-blmf (Blenrep) was voluntarily withdrawn from the US market in November 2022 at the request of the FDA. The withdrawal was driven by lack of confirmed efficacy. It was re‑approved by the FDA on October 23, 2025, with a new indication: belantamab mafodotin-blmf (Blenrep) + bortezomib + dexamethasone (BVd) for adults with relapsed or refractory MM who have received at least two prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.

PEDIATRIC STATUS

The safety and effectiveness in pediatric individuals have not been established.

Description

MULTIPLE MYELOMA

Multiple myeloma (MM) accounts for about 1.8% of all cancers and is most frequently diagnosed in people between 65 and 74 years of age (median age, 69 years). The average lifetime risk of developing MM for the US population is approximately less than1%. In 2025, the American Cancer Society estimates that about 36,110 new cases will be diagnosed (20,030 in men and 16,080 in women). MM, the second most common blood cancer, is a cancer of plasma cells characterized by the rapid proliferation of malignant cells in the bone marrow. These abnormal plasma cells replace healthy cells, infiltrate surrounding tissues, and may lead to life-threatening damage to vital organs. Some individuals diagnosed with MM are initially asymptomatic; however, most individuals are diagnosed based on symptoms such as bone lesions, anemia, fatigue, hypercalcemia, renal dysfunction, or infections. Most individuals with MM will have relapsed or refractory (R/R) disease and require further treatment following first-line therapy. There is a high demand for agents that treat MM that does not respond or that progresses after first- or subsequent-line therapy.

BELANTAMAB MAFODOTIN-BLMF (BLENREP)

Belantamab mafodotin-blmf (Blenrep) is an anti–B-cell maturation antigen (BCMA) antibody-drug conjugate (ADC) and microtubule inhibitor conjugate that targets BCMA, a protein expressed on normal B lymphocytes and MM cells. Upon binding to BCMA, belantamab mafodotin-blmf (Blenrep) is internalized and monomethyl auristatin F (MMAF) is released via proteolytic cleavage, which causes disruption in the microtubule network and eventually cell cycle arrest and apoptosis. In addition to MMAF-induced apoptosis, belantamab mafodotin-blmf (Blenrep) causes tumor cell lysis through antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

Dosage and frequency: 2.5 mg/kg of actual body weight given as an intravenous infusion over approximately 30 minutes once every 3 weeks until disease progression or unacceptable toxicity.

RISK EVALUATION AND MITIGATION STRATEGY (REMS) PROGRAM

The US Food and Drug Administration (FDA) initiated a Risk Evaluation and Mitigation Strategy (REMS) program due to the risk of ocular toxicity associated with the use of belantamab mafodotin-blmf (Blenrep). This program informs professional providers, individuals receiving this drug, healthcare settings, and wholesalers-distributors about the potential risk and outlines processes to ensure the safety of the individuals receiving this drug. Measures include enrollment/certification into the program, counseling, baseline and follow-up ophthalmic examinations, and preservative-free lubricant eye drop use.

PEER-REVIEWED LITERATURE

SUMMARY

The safety and effectiveness of belantamab mafodotin‑blmf (Blenrep) in combination with bortezomib and dexamethasone (BVd) was evaluated in DREAMM‑7, a Phase 3, open‑label, randomized, multicenter study. Adult participants had relapsed or refractory MM and had received at least two prior lines of therapy, including both a proteasome inhibitor and an immunomodulatory agent. Participants were randomly assigned 1:1 to receive belantamab mafodotin‑blmf + bortezomib + dexamethasone (BVd) OR daratumumab + bortezomib + dexamethasone (DVd). The median progression-free survival was 31.3 months in the BVd arm compared with 10.4 months in the DVd arm (hazard ratio, 0.31). Median overall survival was not reached in the BVd arm and 35.7 months in the DVd arm (hazard ratio, 0.49). Ocular adverse reactions were significant, occurring in 92% of participants, with 77% experiencing Grade 3–4 events and 83% requiring dose modification due to ocular toxicity.

OFF-LABEL INDICATION

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

American Cancer Society. Key statistics about multiple myeloma. Updated February 28, 2025. https://www.cancer.org/cancer/types/multiplemyeloma/about/key-statistics.html. Accessed February 2, 2026.

Eastern Cooperative Oncology Group (ECOG). ECOG performance status. 2020. Available at: http://ecog-acrin.org/resources/ecog-performance-status. Accessed February 2, 2026.

Elsevier's Clinical Pharmacology Compendium. belantamab mafodotin-blmf (Blenrep). 11/13/2025. [Clinical Key Web site]. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed February 2, 2026.

Hungria V, Hus M, ChengCheng F, et al. Patient-reported outcomes with belantamab mafodotin, bortezomib, and dexamethasone versus daratumumab, bortezomib, and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-7): results from a phase 3, open-label, randomised controlled trial. Lancet Haemtaol. 2025;12(8):e599-e610.

Hungria V, Robak P, Hus M, et al. Belantamab mafodotin, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2024;391(5):393-407.

Laubach JP. Multiple myeloma: Clinical features, laboratory manifestations, and diagnosis. [UpToDate Web Site]. Updated 08/13/2020. Available at: http://www.uptodate.com/home [via subscription only]. Accessed February 2, 2026.

Lexi-Drugs Compendium. belantamab mafodotin-blmf (Blenrep) . 01/06/2026. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed February 2, 2026.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. belantamab mafodotin-blmf (Blenrep). [NCCN Web site]. 2026. Available at: http://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed February 2, 2026.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Multiple Myeloma. V.5.2026. 01/09/2026. [NCCN Web site]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf [via free subscription]. Accessed February 2, 2026.

Rajkumar SV. Multiple myeloma: Treatment of relapsed or refractory disease. [UpToDate Web site]. 08/10/2020. Available at: http://www.uptodate.com/contents/treatment-of-relapsed-or-refractory-multiple-myeloma?source=search_result&search=daratumumab&selectedTitle=4~10. Accessed February 2, 2026.

Risk Evaluation and Mitigation Strategy (REMS) Program. Blenrep REMS. 2/2/26. Available at: https://www.accessdata.fda.gov/Scripts/Cder/Rems/index.cfm. Accessed February 2, 2026.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. belantamab mafodotin-blmf (Blenrep) prescribing information and approval letter [FDA Web site]. 10/2025. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 2, 2026.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

Report the most appropriate diagnosis code in support of medically necessary criteria as listed in the policy.

HCPCS Level II Code Number(s)

THE FOLLOWING CODE(S) ARE USED TO REPRESENT BELANTAMAB MAFODOTIN-BLMF (BLENREP):

C9399 Unclassified drugs or biologics

J3590 Unclassified biologics

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

BILLING REQUIREMENTS

If there is no specific HCPCS code available for the drug administered, then the drug must be reported with the most appropriate unlisted code along with the corresponding National Drug Code (NDC).

Cross Reference

Policy History

Revisions from MA08.192:

04/20/2026

This is a new policy, effective 04/20/2026. This policy has been redeveloped to communicate the Company's coverage criteria for belantamab mafodotin-blmf (Blenrep).

This policy was established following US Food and Drug Administration (FDA) re‑approval of belantamab mafodotin-blmf (Blenrep) for eligible adult individuals with relapsed or refractory multiple myeloma (RRMM) as third-line therapy in combination with bortezomib and dexamethasone.

Version Effective Date:

4/20/2026

Version Issued Date: