No Correlation Between Baseline Ocular Conditions and Belantamab Mafodotin-Induced Ocular Toxicity in Patients with R/R Myeloma

Rakesh Popat, MD, PhD

Treatment-emergent adverse effects (TEAEs) that may arise with belantamab mafodotin-blmf were not effected by baseline ocular conditions in patients with relapsed/refractory multiple myeloma, according to post hoc analysis results from the phase 2 DREAMM-2 trial (NCT03525678).¹

Findings presented at the 19th International Myeloma Society Annual Meeting also showed that cornea-related ocular TEAEs were more common in patients with cornea-related baseline ocular conditions, such as keratopathy and dry eye.

Among patients who received any duration of belantamab mafodotin who had keratopathy at baseline (n = 103), a 52% increase in keratopathy related to belantamab mafodotin was reported compared with 30% incidence among those who did not have keratopathy at baseline (n = 115). Additionally, in patients with dry eye at baseline (n = 43), there was a 58% increase with treatment compared with a 38% for those who did not (n = 175). The rates of increased blurred vision among patients who did or did not have dry eye at baseline were 44% and 21%, respectively.

“We [must] be taking better care of our patients’ eyes than we currently do. We [must] recommend that our patients have regular, annual ocular visits [which] are optimized as they’re going through their treatments,” Rakesh Popat, MD, PhD, a consultant hematologist and associate professor at the University College London Hospitals NHS Foundation Trust, said in a presentation of the data.

In August 2020, the FDA approved belantamab mafodotin as a treatment for patients with relapsed/refractory multiple myeloma who have received 4 prior therapies, including an immunomodulatory drug (IMiD), a proteasome inhibitor, and an anti-CD38 antibody, based on findings from the DREAMM-2 trial.²

Corneal events and ocular symptoms were associated with belantamab mafodotin treatment on the trial and included in a box warning on the label. The most common ocular symptoms at 13 months of follow-up included blurred vision, decline in best corrected visual acuity, and dry eye.

Though patients with corneal epithelial disease were excluded from enrollement, no other ocular baseline conditions were disallowed including patients with mild punctate keratopathy.

The post hoc analysis examined the relationship between baseline ocular conditions and ocular symptoms reported with belantamab mafodotin.

DREAMM-2 enrolled patients aged least 18 years with histologically or cytologically confirmed multiple myeloma who experienced disease progression after at least 3 prior lines of treatment that included an anti-CD38 antibody. Patients were also required to be refractory to an IMiD and a proteasome inhibitor. Eligible patients needed to have an ECOG performance status of 0 to 2.

Key exclusion criteria included prior allogeneic stem cell transplant, systemic antimyeloma therapy within 14 days of plasmapheresis or within 7 days of the first study dose of belantamab mafodotin, or systemic treatment with high-dose steroids within 14 days of study treatment.

Once enrolled, patients were randomly assigned to receive 2.5 mg/kg or 3.4 mg/kg of belantamab mafodotin intravenously every 3 weeks until disease progression or unacceptable toxicity.

The post hoc analysis examined ocular symptoms related to treatment with belantamab mafodotin to identify symptoms that had at least a 20% difference vs baseline in patients with or without the conditions at baseline. The analysis focused on cornea-related symptoms of keratopathy and dry eye, plus non–cornea-related symptoms including age-related macular degeneration, glaucoma, blepharitis, and visual acuity. The analysis examined patients who received belantamab mafodotin for any duration, for no more than 3 months, and more than 3 months.

Notably, 89.9% of all patients (n = 218) had at least 1 baseline ocular condition. Ocular conditions at baseline included keratopathy (47.2%), dry eye (19.7%), cataract (59.6%), age-related macular degeneration (3.6%), glaucoma (11.9%), and blepharitis (20.6%). Data on age-related macular denegation at baseline was missing in 73.9% of patients. Visual acuity at baseline included 20/30 or better (79.8%), worse than 20/30 and better than 20/50 (12.8%), and worse than 20/50 (7.3%).

An increase of at least 20% was not observed in TEAEs of cataracts, glaucoma, blepharitis, or any visual acuity conditions among patients who received belantamab mafodotin for any duration.

Among patients with baseline age-related macular degeneration (n = 8), a 63% increase was reported following treatment with belantamab mafodotin compared with a 29% increase in patients who did not have age-related macular degeneration at baseline (n = 49). Rates of increase of blurry vision were 38% and 14%, respectively, and rates of increase of diplopia were 25% and 0% among these patients, respectively.

In patients who received 3 months or less of belantamab mafodotin, rates of keratopathy increased by 39% in patients with baseline keratopathy (n = 55) vs a 9% among patients without baseline keratopathy (n = 68). A 20% increase in the rate of dry eye was not met in either group. The only non–cornea-related ocular symptom to increase by more than 20% among patients treated for 3 months or less was age-related macular degeneration, which increased by 60% in patients who had the condition at baseline (n = 5) compared with 12% for those who did not have the condition at baseline (n = 34).

Among patients treated for more than 3 months, there was a 56% increase in keratopathy in those who had the condition at baseline (n = 48) vs 36% for those who did not have keratopathy at baseline (n = 49). A 63% increase was seen in dry eye for patients who had the condition at baseline (n = 23) compared with 60% for those who did not (n = 72). Rates of blurred vision increase were 60% and 40% in patients who did and did not have dry eye at baseline, respectively.

The only non–cornea-related ocular condition where patients saw at least a 20% increase following treatment was visual acuity worse than 20/30 to better than 20/50, where patients with the condition at baseline saw a 46% increase (n = 13) compared with 68% for those who did not fall into that category at baseline (n = 52).

In patients treated longer than 3 months, patients with age-related macular degeneration at baseline (n = 3) saw a 67% increase in blurred vision after treatment compared with 33% for those who did not have macular degeneration at baseline (n = 15). Patients with glaucoma at baseline (n = 11) had a 9% increase in dry eye vs 30% for those who did not have glaucoma at baseline (n = 84). Patients with visual acuity of 20/30 or better at baseline (n = 75) had a 51% increase in blurred vision compared with 30% who did not have 20/30 or better visual acuity (n = 20).

“Our interpretation of this is that those with good eyesight are more likely notice a blurring of their vision and are therefore more likely to present with those AEs,” Popat concluded.

_References

_{1. Popat R, Kazantzi A, Kleinman D, et al. Impact of baseline ocular conditions on belantamab mafodotin (Belmaf)–related corneal events in patients with relapsed or refractory multiple myeloma. Presented at: 19th International Myeloma Society Annual Meeting; August 25-27, 2022; Los Angeles, CA. Abstract OAB-049.}

_{2. FDA approves GSK’s Blenrep (belantamab mafodotin-blmf) for the treatment of patients with relapsed or refractory multiple myeloma. News release. Published August 5, 2020. Accessed August 27, 2022. https://bit.ly/3gxEXB1}