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

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/1.73 m2) 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 of 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 of 3 to 21). The median time to first response was 1.4 months (95 % CI: 1.0 to 1.6). The overall response rate (ORR) was 31 % (97.5 % CI: 21 % to 43 %); 73 % of responders had response durations of greater than or equal to 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.

Belantamab in Combination with Dexamethasone in Patients with Triple-class Relapsed/Refractory Multiple Myeloma

Atieh et al (2022) noted that triple-class relapsed/refractory multiple myeloma (RRMM) has a poor prognosis. These researchers examined the clinical outcomes of belantamab plus dexamethasone (Bd) in the treatment of patients with triple-class RRMM. They identified 35 patients with triple-class RRMM who received Bd at the University of Kansas from October 2019 to November 2021. The median age was 66 years (42 to 85) and the median prior lines of therapy was 5 (3 to 15); 19 (54 %) patients had R-ISS stage III disease, 15 (43 %) patients had high-risk cytogenetics, and 15 patients (43 %) had extra-medullary disease (EMD); 8 patients received prior BCMA-targeted therapy. ORR was 43 %, with 23 % achieving very good partial response (PR) and better. At a median follow-up of 10.7 months, the median progression-free survival (PFS) and overall survival (OS) were 4.9 and 10.7 months, respectively. The most common adverse event (AE) was keratopathy, which occurred in 30 (86 %) patients; 24 patients required dose reduction or delay due to keratopathy. Other common toxicities included anemia (83 %), thrombocytopenia (80 %), neutropenia (34 %), and elevated liver function tests (51 %). The authors concluded that this analysis showed belantamab plus dexamethasone exhibited good activity in triple-class RRMM; and keratopathy remains a challenging AE and the leading cause of dose reduction, delay and treatment cessation.

Belantamab for the Treatment of Light Chain Amyloidosis

Rodriguez et al (2022) noted that light chain (AL) amyloidosis is challenging to diagnose, and it should be considered a cardiac emergency. There has been a great deal of advances in the treatment of AL amyloidosis from initial descriptions of melphalan therapy until the recent approval of the 1st AL amyloidosis specific drug (daratumumab). Comprehension of the pathophysiology and biology of AL amyloidosis is crucial to understanding the major therapeutic targets in which light chain stability remains as a major key target of therapy. Organ dysfunction is a result not only from disruption of organ architecture but also direct cellular toxicity. Novel anti-plasma cell agents for AL like isatuximab (anti CD-38 monoclonal antibody), belantamab (anti-BCMA monoclonal antibody), and elotuzumab (anti-SLAMF7 monoclonal antibody) are currently under investigation. The authors concluded that both diagnostic and therapeutic advances made the future of AL management bright while acknowledging the complexity of this patient population and focusing on a multi-disciplinary approach.

: Requires Precertification:

Precertification of belantamab mafodotin (Blenrep) is required of all Aetna participating providers and members in applicable plan designs. For precertification of belantamab mafodotin (Blenrep), call (866) 752-7021 (Commercial), or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see

For Medicare Part B plans, call (866) 503-0857, or fax (844) 268-7263.

Criteria for Initial Approval

Multiple Myeloma

Aetna considers belantamab mafodotin (Blenrep) medically necessary for treatment of relapsed, refractory, or progressive 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:

Aetna considers all other indications as experimental and investigational (for additional information, see Background section).

Continuation of Therapy

Aetna considers continuation of belantamab mafodotin (Blenrep) therapy medically necessary in members requesting reauthorization for an indication listed in Section I when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

Dosage and Administration

Belantamab mafodotin-blmf is available as Blenrep 100 mg as a lyophilized powder in a single-dose vial for reconstitution and further dilution for intravenous infusion.

Multiple Myeloma

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

Source: GlaxoSmithKline, 2022