Researchers Gain Insight into Eye Side Effects of Blenrep

The blood vessels around the cornea may be the primary pathway by which the antibody-drug conjugate Blenrep (belantamab mafodotin) causes ocular adverse events, finds a case analysis published recently in JAMA Ophthalmology.

The FDA had originally granted accelerated approval of Blenrep in August 2020 as a monotherapy to treat relapsed or refractory multiple myeloma based on the DREAMM-2 endpoint of overall response rate. But in November 2022, Blenrep’s developer, GSK, announced it withdrew Blenrep from the U.S. market at the request of the FDA. Although ocular adverse events were known during clinical development of Blenrep, this was not the reason for the product’s withdrawal. The agency made the request after the DREAMM-3 phase 3 confirmatory failed to meet its endpoint of progression-free survival.

Ocular adverse events, including blurred vision, dry eyes, eye pain, abnormal visual activity, and inflammation of the cornea, occurred in more than half of patients in DREAMM-1, an early study of Blenrep. Patients in the DREAMM-2 study were required to undergo monitoring for ocular events, and recommendations were to lower the dose of Blenrep, especially for those patients who were at risk.

Vivian Lee, M.D.

In the JAMA Ophthalmology analysis, researchers wanted to characterize the corneal changes in patients who had been treated with Blenrep as a treatment for multiple myeloma. Researchers, led by Vivian Lee, M.D., in the department of ophthalmology at the University of Pennsylvania Perelman School of Medicine, screened 16 patients , and nine were enrolled. Six patients had evaluable corneal samples. Researchers also evaluated tear fluid and blood for plasma concentrations of Blenrep.

Researchers found that Blenrep reaches corneal epithelial cells and is associated with pseudomicrocyst formation. Five samples were positive for apoptosis, and three samples showed evidence of inflammation. Antibody drug conjugate was detected in the tear fluid of 5 of 7 patients with tear fluid sampling, while ADC was quantifiable in 3 of 4 patients with blood samples

“The clinical pattern of corneal changes, in which pseudomicrocysts are initially present in the corneal periphery, suggests that limbal vessels are a primary pathway by which ADCs enter the corneal epithelium,” researchers wrote.

The main limitation was the small patient population. “Low patient enrollment and withdrawal of belantamab mafodotin from the market following the result from the DREAMM-3 trial limited the conclusions that can be drawn from small numbers of patients,” researchers wrote.

The study, however, improves the understanding of potential mechanisms behind pseudomicrocyst development during treatment with antibody drug conjugates, researchers said.

Since being removed from the market, GSK has been pursuing research of Blenrep in combination with other therapies. The FDA is currently reviewing Blenrep in combination with bortezomib plus dexamethasone and pomalidomide plus dexamethasone to treat patients with multiple myeloma who have received at least one prior line of therapy. Regulators have assigned a Prescription Drug User Fee Act action date of July 23, 2025.

The application is based on the DREAMM-7 and DREAMM-8 trials, which both met their primary endpoints, showing statistically significant and clinically meaningful improvements in progression-free survival (PFS) for the belantamab mafodotin combinations compared with standard-of-care triplet combinations in relapsed or refractory multiple myeloma. Eye-related side effects in these trials were generally manageable with extended time between infusions and dose reductions.

The Blenrep combinations were approved by UK regulators in April 2025 and just recently by regulators in Japan for patients with multiple myeloma based on data from the DREAMM-7 and DREAMM-8 trials.