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Review
. 2021 May 11:11:678634.
doi: 10.3389/fonc.2021.678634. eCollection 2021.

Ocular Toxicity of Belantamab Mafodotin, an Oncological Perspective of Management in Relapsed and Refractory Multiple Myeloma

Ahsan Wahab  1 , Abdul Rafae  2 , Kamran Mushtaq  3 , Adeel Masood  4 , Hamid Ehsan  5 , Maria Khakwani  6 , Aqsa Khan  7
Affiliations
Review

Ocular Toxicity of Belantamab Mafodotin, an Oncological Perspective of Management in Relapsed and Refractory Multiple Myeloma

Ahsan Wahab et al. Front Oncol. .

Abstract

Belantamab mafodotin (belamaf), an antibody-drug conjugate approved for the treatment of relapsed and refractory multiple myeloma (RRMM), is an anti B-cell maturation antigen (BCMA) agent. DREAMM-1, a first in-human trial of belamaf, reported several ocular toxicities requiring dose adjustments, dose delays and treatment discontinuations. In DREAMM-1, 53% of patients in part-1 and 63% of patients in part-2 had ocular toxicity. Similarly, 73% of patients in DREAMM-2 had keratopathy (71% in 2.5 mg/kg versus 75% in 3.4 mg/kg) with the most common symptoms being blurred vision and dry eyes. Ocular toxicity of belamaf is attributed to microtubule-disrupting monomethylauristatin-F (MMAF), a cytotoxic payload of the drug that causes an off-target damage to the corneal epithelial cells. Ocular adverse events (AEs) of belamaf are more frequent at higher doses compared with lower doses. Higher belamaf dose, history of dry eyes and soluble BCMA are associated with increased risk of corneal toxicity. Absence of ocular symptoms does not exclude the possibility of belamaf-induced ocular toxicity, so patients need slit lamp and Snellen visual acuity testing to detect microcytic-like epithelial changes and visual decline. Corticosteroid eyes drops for 4-7 days prior to belamaf dose do not prevent ocular AEs and may cause steroid-related AEs instead. Keratopathy and Visual Acuity scale (KVA) is recommended to document the severity of belamaf-induced ocular toxicity and make treatment adjustments. Management of toxicity includes dosage modifications, treatment interruption or discontinuations and preservative-free artificial tears along with close ophthalmology and hematology-oncology follow-ups.

Keywords: B-cell maturation antigen; belantamab mafodotin; management; multiple myeloma; ocular toxicity.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Showing Keratopathy and Visual Acuity Scale (KVA) and recommended treatment modifications of Belantamab Mafodotin (BCVA, best corrected visual acuity; belamaf, belantamab mafodotin; G, grade. *Figure is derived from DREAMM-2 guidelines).
See this image and copyright information in PMC

References

    1. Administration UFaD . FDA Granted Accelerated Approval to Belantamab Mafodotin-Blmf for Multiple Myeloma (2020). Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-granted-accel....
    1. Chiu A, Xu W, He B, Dillon SR, Gross JA, Sievers E, et al. . Hodgkin Lymphoma Cells Express TACI and BCMA Receptors and Generate Survival and Proliferation Signals in Response to BAFF and APRIL. Blood (2007) 109(2):729–39. 10.1182/blood-2006-04-015958 - DOI - PMC - PubMed
    1. Huang H-W, Chen C-H, Lin C-H, Wong C-H. Lin K-I. B-Cell Maturation Antigen is Modified by a Single N-Glycan Chain That Modulates Ligand Binding and Surface Retention. Proc Natl Acad Sci (2013) 110(27):10928–33. 10.1073/pnas.1309417110 - DOI - PMC - PubMed
    1. Tai Y-T, Acharya C, An G, Moschetta M, Zhong MY, Feng X, et al. . APRIL and BCMA Promote Human Multiple Myeloma Growth and Immunosuppression in the Bone Marrow Microenvironment. Blood (2016) 127(25):3225–36. 10.1182/blood-2016-01-691162 - DOI - PMC - PubMed
    1. Trudel S, Lendvai N, Popat R, Voorhees PM, Reeves B, Libby EN, et al. . Targeting B-Cell Maturation Antigen With GSK2857916 Antibody–Drug Conjugate in Relapsed or Refractory Multiple Myeloma (BMA117159): A Dose Escalation and Expansion Phase 1 Trial. Lancet Oncol (2018) 19(12):1641–53. 10.1016/S1470-2045(18)30576-X - DOI - PMC - PubMed