In August 2020, the FDA approved the first BCMA-directed antibody-drug conjugate, Blenrep (belantamab mafodotin), for the treatment of patients with relapsed (coming back) or refractory (not responding to therapy) multiple myeloma. This approval was based on the results of the DREAMM-2 clinical trial, which investigated this new BCMA-targeting therapy in patients with multiple myeloma.
At the 2021 ASCO Annual Meeting, Evangelos Terpos, MD, PhD, Professor of Hematology at the National and Kapodistrian University of Athens School of Medicine, in Athens, Greece, presented new results from the DREAMM-2 study, which focused on vision-related symptoms associated with belantamab mafodotin.
Changes in vision could indicate corneal alterations in patients with relapsed or refractory multiple myeloma who are receiving belantamab mafodotin, according to new findings presented at the ASCO meeting.
A new analysis of the results of the DREAMM-2 study showed that severe keratopathy was observed only 7.5% of the time in patients who had no changes or only mild changes in their visual acuity and reported no vision-related (ocular) symptoms.
“The results from this analysis suggest that changes in visual acuity and ocular symptoms in patient-reported outcomes, such as the OSDI [Ocular Surface Disease Index], should be further investigated as possible surrogate markers to help hematologists and oncologists detect meaningful keratopathy (eye inflammation) and inform them as to when it is best to consult an eye care professional for full ophthalmologic exam while receiving belantamab mafodotin treatment,” Dr. Terpos said.
The overall response rate to belantamab mafodotin was approximately 32%, but patients who had a minimal response or better had a duration of response of nearly 11 months, which is one of the longest durations of response to any drug approved for the treatment of patients with refractory myeloma.
According to Dr. Terpos, however, ocular events are a known effect of mafodotin and have occurred in patients treated with belantamab mafodotin.
“Ocular events were common in the DREAMM-2 study and included symptoms such as blurred vision, dry eye, changes in best-corrected visual acuity, and keratopathy, an eye disorder that involves blister-like swelling of the cornea,” said Dr. Terpos. “Microcyst-like epithelial changes were also observed on ocular exams.”
Treatment-related eye side effects in the DREAMM-2 study were managed by reducing the dose of belantamab mafodotin or by delaying the dosing based on results of the eye exam. No patients reported permanent loss of vision during the study.
Patient-Reported Ocular Symptoms
For this analysis that was presented at the ASCO meeting, Dr. Terpos and colleagues investigated the relationship between eye exam findings, best-corrected visual acuity changes, and patient-reported ocular symptoms to determine whether best-corrected visual acuity changes and symptoms could guide the dosing of belantamab, rather than corneal exams.
Adults with relapsed or refractory multiple myeloma who were enrolled in the DREAMM-2 study had received at least 2 previous lines of therapy and did not respond to treatment with immunomodulatory drugs, such as Revlimid (lenalidomide) or proteasome inhibitors, such as Velcade (bortezomib), and did not tolerate an anti-CD38 monoclonal antibody, such as Darzalex (daratumumab), common drugs used for the treatment of multiple myeloma.
Eye exams were performed by ophthalmologists on all patients at the start of the study and before each dose of belantamab mafodotin. Changes in the cornea and best-corrected visual acuity were assessed as per protocol-defined criteria, said Dr. Terpos, with assessment of grade being based on the worse eye.
Ocular symptoms and vision-related functioning were also assessed by questionnaires, including the patient-reported outcomes version of the Common Terminology Criteria for Adverse Events and the Ocular Surface Disease Index.
Most Common Symptoms
In the 95 patients who received belantamab mafodotin, grade 3 to 5 keratopathy was associated with minimal or no changes in best-corrected visual acuity in 12.5% of eye evaluations.
Among patients with grade 3 to 4 keratopathy and no best-corrected visual acuity changes, the most common findings from corneal exams were severe keratopathy (24%) and diffuse microcyst-like epithelial changes (70%).
Severe keratopathy was observed in only 7.5% of the patients, in those who had none or mild best-corrected visual acuity and no ocular symptoms. Dr. Terpos and colleagues also observed a decrease in the number of patients with severe keratopathy and moderate-to-severe best-corrected visual acuity over time. However, patients with symptoms plateaued before diminishing, suggesting that ocular symptoms may persist in the absence of keratopathy or best-corrected visual acuity changes, Dr. Terpos said.
Blurred vision and dry eyes were the most common ocular symptoms in patients with moderate or severe keratopathy. However, severe keratopathy was observed only in 5% of the patients; those patients did not report frequent ocular symptoms most of the time.
“Ocular symptoms may represent surrogates of corneal alterations,” said Dr. Terpos. The findings in this analysis suggest that eye exams and those vision-related symptoms may be used to guide the dosing of belantamab mafodotin by potentially reducing its dose in patients with vision-related symptoms to optimize patient outcomes.