Belantamab mafodotin-blmf for Relapsed or Refractory Multiple Myeloma

Introduction

On August 5, 2020, the FDA granted accelerated approval to belantamab mafodotin-blmf (Blenrep; GlaxoSmithKline).¹

Belantamab mafodotin-blmf is now indicated for adult patients with relapsed or refractory myeloma who have received at least 4 prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immune modulating agent. Belantamab mafodotin-blmf is a first-in-class, anti–B-cell maturation antigen (BCMA) immunoconjugate with afucosylated, humanized immunoglobulin G1 anti-BCMA monoclonal antibody conjugated by a protease-resistant maleimidocaproyl linker to a microtubule-disrupting agent, monomethyl auristatin F (MMAF).² This conjugated drug allows delivery of cytotoxic MMAF to BCMA-expressing multiple myeloma cells causing apoptosis and tumor lysis through antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.

Efficacy

Accelerated approval of belantamab mafodotin-blmf stemmed from the results of the multicenter open-label, phase 2 DREAMM-2 (NCT03525678) study.² The study enrolled patients with relapsed or refractory multiple myeloma with disease progression after 3 or more lines of therapy and who were refractory to immunomodulatory drugs and proteasome inhibitors, and refractory or intolerant to an anti-CD38 monoclonal antibody. The primary end point of patients achieving a partial response or better occurred in 31% (97.5% CI, 20.8-42.6) of patients in the 2.5 mg/kg cohort. Another key secondary end point was probability of having a duration of response 4 months or longer, which was estimated by the Kaplan Meier curve to be 78% (95% CI, 57-89) in the 2.5 mg/kg cohort.

Safety

The most common adverse effects (AEs) were keratopathy (71%), decreased visual acuity (53%), nausea (24%), blurred vision (22%), pyrexia (22%), infusion-related reactions (21%), and fatigue (20%). The most common grade 3 or 4 laboratory abnormalities are decreased platelet count (21%), decreased lymphocytes (22%), decreased hemoglobin level (18%), decreased neutrophils (9%), increased creatine level (5%), and increased γ-glutamyl transferase (5%).3 Because of the risks of ocular toxicity, the medication is restricted under the Risk Evaluation and Mitigation Strategy (REMS) program. Prescribers must be certified with the Blenrep REMS program. Patients must be enrolled in the program and adhere to monitoring.

This medication also carries a black box warning: corneal epithelium changes can occur, resulting in alteration in vision, including severe vision loss and corneal ulcer, and symptoms such as blurred vision and dry eyes. Ophthalmic examinations should occur at baseline (3 weeks prior to the first dose), prior to each dose (at least 1 week after previous dose and within 2 weeks prior to next dose), and promptly for worsening symptoms.

Patients should be advised to use preservative-free lubricant eye drops at least 4 times per day starting with the first infusion and continuing until end of treatment, to avoid contact lens use, and to use caution when driving. Complete blood counts should occur at baseline and as clinically indicated thereafter. If applicable, patients should use contraception while on this medication because of the potential of embryo-fetal toxicity. Female patients of reproductive potential should continue to use contraception 4 months after the last dose and male patients with female partners of reproductive potential should use contraception for 6 months after the last dose.³

Dosing

The recommended belantamab mafodotin-blmf dose is 2.5 mg/kg as an intravenous infusion over approximately 30 minutes once every 3 weeks. For AEs requiring dose reductions, decrease to 1.9 mg/kg intravenously once every 3 weeks.³

References

1. FDA granted accelerated approval to belantamab mafodotin-blmf for multiple myeloma. FDA. August 5, 2020. Accessed November 18, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-granted-accelerated-approval-belantamab-mafodotin-blmf-multiple-myeloma#:~:text=On%20August%205%2C%202020%2C%20the,antibody%2C%20a%20proteasome%20inhibitor%2C%20and
2. Lonial S, Lee HC, Badros A, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. Lancet Oncol. 2020;21(2):207-221. doi:10.1016/S1470-2045(19)30788-0
3. Blenrep. Prescribing information. GlaxoSmithKline; 2020. Accessed November 18, 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761158s000lbl.pdf