Belantamab Mafodotin-blmf (Blenrep)

Number: 0981

Policy

Note: REQUIRES PRECERTIFICATION

Precertification of belantamab mafodotin (Blenrep) is required of all Aetna participating providers and members in applicable plan designs. For precertification, call (866) 752-7021 (Commercial), (866) 503-0857 (Medicare), or fax (866) 267-3277.

Aetna considers belantamab mafodotin (Blenrep) medically necessary for treatment of relapsed or refractory multiple myeloma as a single agent in members who have received at least 4 prior therapies, including at least one drug from each of the following categories:

• Anti-CD38 monoclonal antibody (e.g., daratumumab)
• Proteasome inhibitor (e.g., bortezomib, ixazomib, or carfilzomib)
• Immunomodulatory agent (e.g., lenalidomide or pomalidomide).

Aetna considers continuation of belantamab mafodotin (Blenrep) medically necessary when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

Aetna considers all other indications for belantamab mafodotin-blmf (Blenrep) experimental and investigational because its effectiveness for other indications has not been established.

Dosing Recommendations

The recommended dosage is 2.5 mg/kg as an intravenous infusion over approximately 30 minutes once every 3 weeks. 

Source: GlaxoSmithKline 202

Background

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

• Blenrep is indicated for the treatment of 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.

Multiple myeloma is a malignant neoplasm of plasma cells that accumulate in the bone marrow, leading to bone destruction and marrow failure. Multiple myeloma accounts for about 1.8% of all cancers and slightly over 17% of hematologic malignancies in the United States. The American Cancer Society has estimated about 32,270 new cases of multiple myeloma in the United States in 2020, with an estimated 12,830 deaths (American Cancer Society, 2020).

On August 5, 2020, the Food and Drug Administration granted accelerated approval to belantamab mafodotin-blmf (Blenrep) for adult patients 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. Belantamab mafodotin-blmf is a B-cell maturation antigen (BCMA)-directed antibody and microtubule inhibitor conjugate that directly targets a B-cell maturation antigen (BCMA) a protein on the surface on myeloma cells. The efficacy of belantamab mafodotin-blmf was evaluated in DREAMM-2 (NCT 03525678), an open-label, multicenter trial. Eligible patients had relapsed or refractory multiple myeloma, had previously received 3 or more prior therapies, including an anti-CD38 monoclonal antibody, and were refractory to an immunomodulatory agent and a proteasome inhibitor. Patients had measurable disease by International Myeloma Working Group (IMWG) criteria. Patients with corneal epithelial disease, except mild punctate keratopathy, at baseline were excluded from the study. Patients with mild or moderate renal impairment (eGFR 30 to 89 mL/min/1.73m2 ) at baseline were also eligible for the study. Patients received either belantamab mafodotin-blmf 2.5 mg/kg or 3.4 mg/kg intravenously once every 3 weeks until disease progression or unacceptable toxicity. The major efficacy outcome measure was overall response rate as evaluated by an Independent Review 18 Committee (IRC) based on the IMWG Uniform Response Criteria for Multiple Myeloma. A total of 97 patients received belantamab mafodotin-blmf at a dose of 2.5 mg/kg administered intravenously once every 3 weeks. The median age was 65 years (range: 39 to 85 years), 53% were male, 74% were White, and 16% were Black. Most patients (77%) were International Staging System (ISS) Stage II or III, 87% had received prior autologous stem cell transplantation (ASCT), and 16% had an Eastern Cooperative Oncology Group (ECOG) performance status of 2. High-risk cytogenetic factors (presence of t[4;14], t[14;16] and 17p13del) were present in 27% of patients. The median number of prior lines of therapy was 7 (range: 3 to 21). The median time to first response was 1.4 months (95% CI: 1.0, 1.6). The ORR was 31% (97.5% CI: 21%, 43%). Seventy-three percent of responders had response durations ≥6 months. These results were observed in patients receiving the recommended dose of 2.5 mg/kg. The authors noted that 2.5 mg/kg was selected as the recommended dose for future studies with belantamab mafodotin, given the similar efficacy and a more favorable safety profile compared with the 3.4-mg/kg dose. Overall, the median duration of response (DOR) was not reached.

There is a boxed warning in the prescribing information cautioning that belantamab mafodotin-blmf causes changes in the corneal epithelium resulting in alterations in vision, including severe vision loss and corneal ulcer, and symptoms, such as blurred vision and dry eyes. Therefore, ophthalmic exams at baseline, prior to each dose, and promptly for worsening symptoms should be conducted. Because of the risks of ocular toxicity, belantamab mafodotin-blmf is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the BLENREP REMS.

Adverse reactions in 20% or more of patients who received belantamab mafodotin-blmf were keratopathy, decreased visual acuity, nausea, blurred vision, pyrexia, infusion-related reactions, and fatigue.

The recommended belantamab mafodotin-blmf dose is 2.5 mg/kg as an intravenous infusion over approximately 30 minutes once every 3 weeks.

Table: CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+" :
Other CPT codes related to the CPB:
96413 - 96417	Chemotherapy administration
HCPCS codes covered if selection criteria are met:
C9069	Injection, belantamab mafodontin-blmf, 0.5 mg
Other HCPCS codes related to the CPB:
Ixazomib, Lenalidomide, Pomalidomide - No specific code:
C9062	Injection, daratumumab 10 mg and hyaluronidase-fihj
J9041	Injection, bortezomib, 0.1 mg
J9044	Injection, bortezomib, not otherwise specified, 0.1 mg
J9047	Injection, carfilzomib, 1 mg
J9145	Injection, daratumumab, 10 mg
ICD-10 codes covered if selection criteria are met:
C90.00 - C90.02	Multiple myeloma

The above policy is based on the following references: