Visualization of Keratopathy Associated With the Antibody-Drug Conjugate Belantamab Mafodotin Using Infrared Imaging in Patients With Multiple Myeloma

Abstract

Purpose: The treatment of patients with relapsed/refractory multiple myeloma (RRMM) with the antibody-drug conjugate belantamab mafodotin is affected by ocular adverse effects, most frequently keratopathy with corneal microcyst-like epithelial changes (MECs). To assess ocular side effects, the Keratopathy and Visual Acuity (KVA) scale, based on the extent of keratopathy subjectively graded on slit-lamp examination and the change in best corrected visual acuity from baseline, was created. Advanced corneal imaging techniques have been explored to further characterize MECs and identify objective imaging biomarkers. We examined whether infrared reflectance imaging of the anterior segment (AS-IR) could contribute to the assessment, monitoring, and documentation of corneal toxicity in patients treated with belantamab mafodotin.

Methods: In addition to the KVA examination, AS-IR imaging was performed. AS-IR images were evaluated for presence of visible hyporeflective lesions and their spatial and temporal distribution between visits and compared with keratopathy identified on slit-lamp examination. To standardize the assessment, a scoring system for lesions on AS-IR was implemented for additional analysis.

Results: Nine patients undergoing treatment with belantamab mafodotin for up to 9 months were examined. All patients exhibited hyporeflective lesions on AS-IR imaging, indicative of corneal toxicity corresponding to MECs observed on slit-lamp examination. AS-IR lesions showed early occurrence, variable quantity and size, and distinct distribution patterns, correlating with clinical findings during treatment.

Conclusions: As shown for belantamab mafodotin, AS-IR imaging represents a fast, noninvasive, supplemental method for documentation, monitoring, and assessment of corneal adverse effects during treatment with antibody-drug conjugates, which may enable more standardized analyses.

FIGURE 1.

Segmentation and scoring system of AS-IR images for analysis. Left side: Segmentation of the corneal surface into 3 zones (central 4 mm, paracentral 8 mm, and peripheral >8 mm in diameter from the center point of the cornea) and four quadrants. Right side: Scoring system for visible corneal alterations on AS-IR. 0 to 4 points were awarded for each quadrant based on appearance of AS-IR alterations, and a cumulative score was calculated per zone for each eye.

FIGURE 2.

Slit-lamp image (A) showing multiple MECs (blue arrowheads) corresponding to hyporeflective lesions (white arrowheads) on an en face corneal infrared image (B).

FIGURE 3.

Multimodal imaging of patient C showing the slit-lamp image (top row) and corresponding en face corneal infrared image (bottom row) at (A) week 3, (B) week 6, (C) week 9, (D) week 19, and (E) week 24.

FIGURE 4.

Anterior segment OCT of patient C at (A) week 3. White arrowheads indicate hyperreflective bands corresponding to areas of confluent hyporeflective lesions on AS-IR images. Note the additional area of hyperreflective signals at the subepithelial layer (blue arrowhead) and at (G) week 24 showing hyperreflective band and epithelial substance defect (red arrowhead).

FIGURE 5.

En face infrared corneal images of patient F showing changing distribution of hyporeflective lesions moved during Blenrep treatment at different time points: (A) week 3: follow-up visit after treatment initiation; (B) week 4; (C) week 5: during treatment pause; (D) week 6: treatment resumed at reduced dose; (E) week 8; (F) week 17; (G) week 50: 10 weeks after treatment termination; (H) week 57: 17 weeks after treatment termination, no more MECs visible on slit-lamp examination.

FIGURE 6.

Scatter plots showing the cumulative score of corneal alterations on AS-IR imaging of the cornea in relation to loss of BCVA from baseline examination in LogMAR.