Coverage Policy Manual
Policy #: 2020024
Category: Pharmacy
Initiated: October 2020
Last Review: October 2025
  Belantamab mafodotin-blmf (e.g., Blenrep)
Description:
Belantamab mafodotin-blmf is an anti-B cell maturation antigen (BCMA) antibody, conjugated to a microtubule disrupting agent- monomethyl auristatin- via a stable, protease resistant linker. It is first in its class. Belantamab mafodotin is indicated for the treatment of adult patients with relapsed or refractory MM who have received at least 4 prior lines of therapy.
 
Belantamab mafodotin has a black-box warning regarding ocular toxicity. It states that belantamab mafodotin has caused changes in the corneal epithelium resulting in changes in vision, including severe vision loss and corneal ulcer, and symptoms, such as blurred vision and dry eyes. Ophthalmic exams are to be performed prior to each dose, and promptly for worsening symptoms.
 
Due to the risks of ocular toxicity, belantamab mafodotin is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the BLENREP REMS.
 
Regulatory Status
 
On August 5, 2020, the FDA granted accelerated approval to belantamab mafodotin-blmf for adults with relapsed or refractory multiple myeloma who have received at least 4 prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.
 
On November 22, 2022, GSK announced the market withdrawal of Belantamab mafodotin-blmf (e.g., Blenrep) following the request of the FDA. The request was based on the previously announced outcome of the DREAMM-3 phase III confirmatory trial, which did not meet the requirements of the FDA Accelerated Approval regulation. As part of GSK’s efforts to ensure physicians and patients are supported during this important time, patients already enrolled in the Blenrep Risk Evaluation and Mitigation Strategy (REMS) program will have the option to enroll in a compassionate use program to continue to access treatment.
 
Belantamab mafodotin-blmf (e.g., Blenrep) was approved by the U.S. Food and Drug Administration (FDA) on October 23, 2025, in combination with bortezomib and dexamethasone for the treatment of adult individuals with relapsed or refractory multiple myeloma who have received at least two prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.
 
Coding
 
See CPT/HCPCS Code section below.
 
 
Policy/
Coverage:
Effective February 19, 2026, for members of plans that utilize an oncology benefits management program, Prior Approval is required for this service when rendered for oncologic indications and is managed through the oncology benefits management program.
 
Prior approval is required for Belantamab mafodotin-blmf (e.g., Blenrep).
 
INITIAL AND CONTINUATION APPROVAL will be for duration of the treatment course or 12 months (whichever comes first). Approval timeframes may differ for members/participants of Self-Insured plans.
 
Effective February 19, 2026
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Belantamab mafodotin-blmf (e.g., Blenrep) meets member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes or for members with contracts without Primary Coverage Criteria, is considered Medically Necessary and is covered, when ALL the following criteria are met:
 
FDA Labeled Indications
 
The use of this drug is covered if an FDA-approved oncologic indication exists [not listed as an indication below with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”).
 
INITIAL APPROVAL:
 
1. Individual is 18 years of age and older (Blenrep, 2025); AND
2. Individual has a diagnosis of relapsed or refractory multiple myeloma (Blenrep, 2025); AND
3. Belantamab mafodotin-blmf (e.g., Blenrep) will be used in combination with bortezomib and dexamethasone (Blenrep, 2025); AND
4. Individual has received at least two prior lines of therapy, including a proteasome inhibitor (i.e., bortezomib or carfilzomib) and an immunomodulatory agent (i.e., thalidomide, lenalidomide, or pomalidomide) (Blenrep, 2025; NCCN 1); AND
5. Eastern Cooperative oncology Group (ECOG) performance status of 0 to 2.
 
CONTINUATION OF THERAPY:
 
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit from continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread.
 
Off-label Indications
 
The use of this drug for off-label indications not listed below is subject to policy 2000030.
 
INITIAL APPROVAL:
 
1. Individual has a diagnosis of relapsed/refractory multiple myeloma (NCCN 2A); AND
2. Individual has received at least three prior lines of therapy for the treatment of multiple myeloma (NCCN 2A).
 
CONTINUATION OF THERAPY:
 
1. Individual continues to meet the initial approval criteria; AND
2. Individual experiences objective benefit from continued treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread.
 
Please see the NCCN Drugs and Biologics Compendium for a complete list of NCCN 1 & 2A indications. To view the most recent and complete version of the guideline or Compendium, go online to NCCN.org. Please note, NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
 
Does Not Meet Primary Coverage Criteria Or Is Not Covered For Contracts Without Primary Coverage Criteria
 
Belantamab mafodotin-blmf (e.g., Blenrep), for any indication or circumstance not described above, does not meet member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes and is not covered.
 
For members with contracts without Primary Coverage Criteria, Belantamab mafodotin-blmf (e.g., Blenrep), for any indication or circumstance not described above, is considered not Medically Necessary or is investigational and is not covered. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
POLICY GUIDELINES
 
Prescribing provider responsible for ensuring individual has ophthalmic exams at baseline, before each dose, promptly for new or worsening symptoms, and as clinically indicated.
 
ECOG Performance Status Scale
 
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 housework, office work
2 = Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
3 = Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
4 = Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
5 = Dead  
 
DOSAGE AND ADMINISTRATION
 
For FDA labeled indications, Belantamab mafodotin-blmf (e.g., Blenrep) must be dosed in accordance with the indication specific recommended dose per FDA label unless otherwise specified below.
 
For off-label indications, authorizations will not exceed the maximum FDA labeled dose and frequency across all the FDA labeled indications unless higher dose is allowed for the specific indication below.
 
The recommended dose of Belantamab mafodotin-blmf (e.g., Blenrep), in combination with bortezomib and dexamethasone, is 2.5 mg/kg as an intravenous infusion over 30 minutes once every 3 weeks for 8 cycles, followed by Belantamab mafodotin-blmf (e.g., Blenrep) 2.5 mg/kg every 3 weeks as a single agent.  
 
Belantamab mafodotin-blmf (e.g., Blenrep) is available for injection as 70 mg of lyophilized powder in a single-dose vial.
 
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Effective January 1, 2023 to February 18, 2026
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Belantamab mafodotin-blmf does not meet member benefit certificate primary coverage criteria that there be scientific evidence in improving health outcomes.
 
For members with contracts without primary coverage criteria, belantamab-mafodotin-blmf is considered investigational.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective October 2022  to December 31, 2022
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of belantamab mafodotin -blmf meets primary coverage criteria in adults with relapsed or refractory multiple myeloma who meet ALL the following criteria (NCCN 2A):
 
    1.  Must be >18 years old AND
    2.  Must have documentation of relapsed or refractory multiple myeloma AND
    3.  Must have documentation of having had 4 prior lines of therapy, including:
a.  an anti-CD monoclonal antibody AND
b.  a proteasome inhibitor AND  
c.  An immunomodulatory agent AND
4.  Must perform an ophthalmic exam prior to initiation of belantamab and prior to each dose of belantamab AND
5.  Have an ECOG status of 0-2 AND
6.  Must be dosed in accordance with the FDA label unless otherwise specified.
 
The use of this drug is covered if a FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).
 
Dosage and Administration
The recommended dosage of belantamab-mafodotin-blmf is 2.5 mg/kg of actual body weight IV over approximately 30 minutes once every 3 weeks until disease progression or unacceptable toxicity.
 
See FDA labeling for dosage modifications for corneal adverse reactions and other adverse reactions.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Belantamab mafodotin-blmf does not meet member benefit certificate primary coverage criteria for any other indication.
 
For members with contracts without primary coverage criteria, belantamab-mafodotin-blmf is considered investigational for any other indication.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective November 1, 2021 to September 2022
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of belantamab mafodotin -blmf (Blenrep™), meets primary coverage criteria in adults with relapsed or refractory multiple myeloma who meet all the following criteria (NCCN 2A):
 
    1.  Must be >18 yrs old.
    2.  Must have documentation of relapsed or refractory multiple myeloma.
    3.  Must have documentation of having had 4 prior lines of therapy, including
a.  an anti-CD monoclonal antibody,
b.  a proteasome inhibitor, AND  
c.  an immunomodulatory agent
4.  Must perform an ophthalmic exam prior to initiation of belantamab and prior to each dose of belantamab
5.  Have an ECOG status of 0-2.
 
The use of this drug is covered if a FDA-approved oncologic indication exists (not listed as an indication above) with the member meeting all of the additional requirements of the prescribing information (package insert listed in the “Indications and Usage”) AND/OR a NCCN category 1 or 2A recommendation is recognized in the NCCN Drugs and Biologics Compendium with the member meeting specified criteria (See policy #2000030).
 
Dosage and Administration
 
The recommended dosage of belantamab-mafodotin-blmf (Blenrep™) is 2.5 mg/kg of actual body weight IV over approximately 30 minutes once every 3 weeks until disease progression or unacceptable toxicity.
 
See FDA labeling for dosage modifications for corneal adverse reactions and other adverse reactions.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Belantamab mafodotin-blmf (Blenrep) does not meet member benefit certificate primary coverage criteria for any other indication.
 
For members with contracts without primary coverage criteria, belantamab-mafodotin-blmf (Blenrep™) is considered investigational for any other indication.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage
 
 
Effective October 2020 to October 31, 2021
 
Policy/Coverage
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of belantamab mafodotin -blmf (Blenrep™), meets primary coverage criteria in adults with relapsed or refractory multiple myeloma who have received at least 4 lines of therapy who meet all the following criteria:
 
  1.  Must be >18 yrs old.
  2.  Must have documentation of relapsed or refractory multiple myeloma.
  3.  Must have documentation of having had 4 prior lines of therapy, including
a.  an anti-CD monoclonal antibody,
b.  a proteasome inhibitor, AND  
c.  an immunomodulatory agent
4.  Must perform an ophthalmic exam prior to initiation of belantamab and prior to each dose of belantamab
5.  Have an ECOG status of 0-2.
 
NCCN 1, 2A and 2B recommendations are covered in accordance with Coverage Policy #2000030
 
Dosage and Administration
The recommended dosage of belantamab-mafodotin-blmf (Blenrep™) is 2.5 mg/kg of actual body weight IV over approximately 30 minutes once every 3 weeks until disease progression or unacceptable toxicity.
 
See FDA labeling for dosage modifications for corneal adverse reactions and other adverse reactions.
 
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Belantamab mafodotin-blmf (Blenrep) does not meet member benefit certificate primary coverage criteria for any other indication.
 
For members with contracts without primary coverage criteria, belantamab-mafodotin-blmf (Blenrep™)
is considered investigational for any other indication.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage
Rationale:
The efficacy and safety of belantamab mafodotin-blmf (Blenrep) was evaluated in a randomized, open-label, multicenter phase 2 clinical trial of 196 patients with relapsed and refractory multiple myeloma with disease progression after three or more lines of therapy and were refractory to immunomodulatory drugs and proteasome inhibitors, and refractory or intolerant (or both) to an anti-CD38 monoclonal antibody (DREAMM-2 trial; NCT03525678). Patients were excluded from the trial with corneal epithelial disease at baseline, except mild punctate keratopathy. They received either belantamab mafodotin 2.5 mg/kg (n=97) or 3.4 mg/kg (n=99) intravenously once every 3 weeks until disease progression or unacceptable toxicity. The primary outcome was overall response rate, which was 31% (30/97; 97.5% CI 20.8-42.6) in the 2.5 mg/kg cohort and 34% (34/99; CI 23.9-46.0) in the 3.4 mg/kg cohort. The most common grade 3-4 adverse events in the safety population were keratopathy in 26 (27%) of 95 patients in the 2.5 mg/kg cohort and 21 (21%) of 99 patients in the 3.4 mg/kg cohort.  Two deaths were potentially related, one case of sepsis in the 2.5 mg/kg cohort and one case of hemophagocytic lymphohistiocytosis in the 3.4 mg/kg cohort.
 
 In this study, single agent belantamab mafodotin resulted in clinically meaningful activity in patients with relapsed or refractory multiple myeloma. The median duration of response was not reached but duration of follow-up was short. The median progression-free survival was 2.9 months in the 2.5 mg/kg cohort and 4.9 months in the 3.4 mg/kg cohort.  The most common reason for treatment discontinuation was keratopathy.
 
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through October 2021. No new literature was identified that would prompt a change in the coverage statement.
 
October 2022 Update
On the basis of the DREAMM-2 study single-agent belantamab mafodotin (belamaf) was approved for patients with relapsed or refractory multiple myeloma (RRMM) who received ≥4 prior therapies, including anti-CD38 therapy. The authors investigated longer term efficacy and safety outcomes in DREAMM-2 after 13 months of follow-up among patients who received belamaf 2.5 mg/kg.
 
DREAMM-2 is an ongoing, phase 2, open-label, 2-arm study investigating belamaf (2.5 or 3.4 mg/kg) in patients with RRMM who had disease progression after ≥3 lines of therapy and were refractory to immunomodulatory drugs and proteasome inhibitors and refractory and/or intolerant to an anti-CD38 therapy. The primary outcome was the proportion of patients that achieved an overall response, assessed by an independent review committee.
 
As of January 31, 2020, 10% of patients still received belamaf 2.5 mg/kg. Thirty-one of 97 patients (32%; 97.5% confidence interval [CI], 21.7%-43.6%) achieved an overall response, and 18 responders achieved a very good partial response or better. Median estimated duration of response, overall survival, and progression-free survival were 11.0 months (95% CI, 4.2 months to not reached), 13.7 months (95% CI, 9.9 months to not reached), and 2.8 months (95% CI, 1.6-3.6 months), respectively. Response and survival outcomes in patients who had high-risk cytogenetics or renal impairment were consistent with outcomes in the overall population. Outcomes were poorer in patients with extramedullary disease. In patients who had a clinical response and prolonged dose delays (>63 days; mainly because of corneal events), 88% maintained or deepened responses during their first prolonged dose delay. Overall, there were no new safety signals during this follow-up.
 
Extended follow-up confirms sustained clinical activity without new safety signals with belamaf in this heavily pretreated patient population with RRMM. (Lonial S, Lee HC, Badros A, et.al., 2021)
 
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2023. No new literature was identified that would prompt a change in the coverage statement.
 
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2024. No new literature was identified that would prompt a change in the coverage statement.
 
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through September 2024. No new literature was identified that would prompt a change in the coverage statement.
 
December 2025 Update
Belantamab mafodotin (belamaf) combined with standard therapies demonstrated significant progression-free survival (PFS) and overall survival benefits in DREAMM-7 and PFS benefit in DREAMM-8 in relapsed/refractory multiple myeloma. Belamaf dose modifications managed adverse events, including belamaf-related ocular events. Ocular events included ocular adverse reactions (eg, dry eyes, photophobia, eye irritation) and protocol-mandated ophthalmic examination findings. Protocol-recommended dose modifications for ocular events were driven by ophthalmic examination findings and included belamaf dose delays until resolution and reductions. Descriptive analyses was used to evaluate the impact of dose modifications on management of ocular events and treatment efficacy. In patients with normal baseline vision who were receiving treatment, dose modifications extended belamaf dosing intervals to a median of 8 to 12 weeks by 9 months; the prevalences of reduced vision to bilateral 20/50 or worse and ocular adverse reactions were highest in the first 3 months and remained low at later time points. Median time to resolution after grade ≥2 ophthalmic examination findings was 12 weeks. Rates of belamaf discontinuations due to ocular events were low. Almost all responders (≥ PR) required dose modifications. Most patients achieved a response prior to an extended (>2 cycles) dose delay; the majority of those who had not, subsequently achieved or deepened their response. In DREAMM-7 and DREAMM-8, median PFS in patients with ≥1 dose delay of ≥12 weeks was 36.6 months and not reached, respectively. Ocular events were common but effectively managed with dose modifications, allowing patients to remain on treatment and derive robust efficacy benefit. (ClinicalTrials.gov identifier: NCT04246047 [DREAMM-7] and NCT04484623 [DREAMM-8]). (Mateos, 2025)
CPT/HCPCS:
C9399Unclassified drugs or biologicals
J3590Unclassified biologics
J9999Not otherwise classified, antineoplastic drugs
References: Belantamab mafodotin. In Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.: 2020. URL: http://www.clinicalpharmacology.com. Updated periodically. Subscription required to view.

BLENREP [package insert]. Brentford, Middlesex, UK: GlaxoSmithKline, 2020

Food and Drug Administration.(2020) FDA granted accelerated approval to belantamab mafodotin-blmf for multiple myeloma. Retrieved from https://www.fda.gov/drugs/drug-approvals-and-databases/fda-granted-accelerated-approval-belantamab-mafodotin-blmf-multiple-myeloma. Last accesses 10/20/2020.

Lonial S, Lee HC, Badros A, et al.(2020) Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. Lancet Oncol. 2020 Feb;21(2):207-221. doi: 10.1016/S1470-2045(19)30788-0. Epub 2019 Dec 16. DOI: 10.1016/S1470-2045(19)30788-0

Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, Abdallah AO, Callander N, Sborov D, Suvannasankha A, Weisel K, Voorhees PM, Womersley L, Baron J, Piontek T, Lewis E, Opalinska J, Gupta I, Cohen AD.(2021) Longer term outcomes with single-agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13-month follow-up from the pivotal DREAMM-2 study. Cancer. 2021 Nov 15;127(22):4198-4212. doi: 10.1002/cncr.33809. Epub 2021 Jul 27. PMID: 34314018; PMCID: PMC8597112.
Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants.
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