A new cohort study reports that soluble B-cell maturation antigen is present in the lacrimal fluid of multiple myeloma patients, with evidence of pinocytosis as the underlying mechanism contributing to the development of keratopathy in these patients.
Belantamab is an anti-B-cell maturation antigen (anti-BCMA) antibody–drug conjugate approved for the pharmacological treatment of refractory multiple myeloma. This treatment is indicated for patients demonstrating progress on anti-CD38 treatment or those who are not eligible candidates for bispecifics and CAR-T treatment.
Belantamab-mediated cytotoxicity in the cornea can be reduced by the pharmacological suppression of pinocytosis. While the cornea does not express the antigen, soluble BCMS (sBCMA) sheds from the corneal cell membrane to circulate in the blood.
This study investigated the presence of sBCMA in the lacrimal fluid of multiple myeloma patients and demonstrated belantamab uptake by the corneal epithelium. The study’s findings are published in the journal Hematologica.
Soluble BCMA in Lacrimal Fluid Correlates With Serum BCMA
The study cohort was composed of seven healthy individuals and nine multiple myeloma patients. The multiple myeloma patients with active disease and controlled disease had significantly higher levels of sBCMA compared to healthy controls. BCMA-coding TNFRSF17 was not expressed in various cell lines tested.
Belantamab in Human Telomerase-Immortalized Corneal Epithelium
Belantamab was associated with the dose-dependent killing of human telomerase-immortalized corneal epithelial (hTcEpi) cells. The corneal epithelial cells were found to be sensitive to the side effects of monomethyl auristatin F (MMAF), which acts via pinocytosis instead of demonstrating targeted killing properties.
Inhibition of Pinocytosis Reduces Cell Killing in hTcEpi Cells
Pretreatment of the hTcEpi cells with the pinocytosis inhibitor EIPA reduced the belantamab-related killing of these cells by reducing the uptake of sBCMA-bound belantamab. The ability of the hTcEpi cells to absorb sBCMA-belantamab and belantamab depends on pinocytosis, which may also explain corneal toxicity in patients on belantamab treatment.
Lacrimal Fluid sBCMA Levels Predispose to Keratopathy
The presence of sBCMA in the lacrimal fluid could be detected prior to the development of keratopathy in multiple myeloma patients on belantamab treatment.
Source:
Munawar, U., Theuersbacher, J., Steinhardt, M., Zhou, X., Han, S., Nerreter, S., Vogt, C., Kurian, S. M., Keller, T., Regensburger, A., Teufel, E., Mersi, J., Bittrich, M., Seifert, F., Haider, M. S., Rasche, L., Hillenkamp, J., Einsele, H., Kampik, D., . . . Waldschmidt, J. M. (2024). Soluble B-cell maturation antigen in lacrimal fluid as a potential biomarker and mediator of keratopathy in multiple myeloma. Haematologica. https://doi.org/10.3324/haematol.2024.285205
