Proactive Care Is Required to Manage Belantamab Mafodotin–Associated Keratopathy in Myeloma

Sarah Sunshine, MD

The use of belantamab mafodotin-blmf (Blenrep) has been linked to varying levels of keratopathy in the treatment of patients with relapsed or refractory multiple myeloma, and early vigilance is required to address these adverse effects (AEs), according to Sarah Sunshine, MD.

Patients who receive belantamab mafodotin can encounter mild, moderate, or severe forms of keratopathy, and Sunshine said management of these AEs should begin before the start of treatment. Between the care of oncologists and consultations with ophthalmologists, a multidisciplinary approach can benefit patients, Sunshine added.

“If I am concerned that there is a higher grade of keratopathy or that there has been an acute change in [vision in] these patients, I reach out directly to the oncologist and let them know,” Sunshine said. “The ophthalmologist has to see these patients within a few days before [each infusion], so [oncologists and ophthalmologists] need to be in close communication.”

In an interview with OncLive^®, Sunshine, assistant professor, Ophthalmology and Visual Sciences, and member, Program in Oncology, University of Maryland School of Medicine, discussed the management of keratopathy associated with belantamab mafodotin treatment in patients with multiple myeloma and explained why ophthalmologists play a vital role in addressing these AEs.

OncLive^®: Can you speak to the differences between mild, moderate, and severe keratopathy associated with belantamab mafodotin treatment in multiple myeloma?

Sunshine: Belantamabmafodotinis a BCMA-directed treatment for treatment-refractory multiple myeloma. About 75% of the patients experience some sort of corneal toxicity, which is keratopathy, and it is usually described as either microcystic-like epithelial changes or superficial punctate keratopathy. [Keratopathy] can cause either no symptoms, blurry vision, or dry-eye symptoms.

Mild-to-moderate keratopathy is described as nonconfluent, microcystic-like changes that are predominantly in the periphery. What is interesting about these changes is they start in the periphery, and they work their way in. When you stop treatment or [a patient’s] symptoms get better, [the symptoms retreat to the periphery before resolving].

The other [aspect of how we define mild-to-moderate keratopathy involves] best-corrected visual acuity. If there has only been a change in 1 line of the Snellen visual acuity, which is our standard way of measuring vision, then that is still considered mild [keratopathy]. Moderate [keratopathy] is [defined by] 2 to 3 lines [of change] on the Snellen Chart but no worse than 20/200 vision.

Severe keratopathy is more of a diffuse, confluent corneal change; it is a combination of these microcystic epithelial cysts and punctate keratopathy, which is a breakdown of the epithelial cells, the skin of the cornea. Because [the cornea] is central, [severe keratopathy] is accompanied with a worsening of vision of at least 2 to 3 lines on the Snellen Chart.

The most severe form of [keratopathy] is when there is an epithelial defect or loss of the skin of the cornea. That js usually accompanied with worse than 20/200 vision. That is what we are trying to prevent here.

What steps should be taken to manage these AEs in this patient population? Is there a one-size-fits-all approach for these patients?

This is where I find it challenging as an ophthalmologist. We do not have great treatment options [for keratopathy]. The only thing that has been helpful is lubrication with artificial tears. The other treatments have not been shown to work. Steroids, antibiotics, and other treatment has not helped patients [manage keratopathy].

From a treatment standpoint, artificial tears and lubrication are the most important things. I try to get these patients on artificial tears preemptively. At the first visit before patients start treatment, I start artificial tears to increase the lubrication, and then we can increase its use from there. My personal favorite is preservative-free artificial tears because [patients] can use them as often as they want.

The only other option that we have is holding treatment. What is promising is that when you do hold treatment, those corneal changes tend to regress. The exact timing is variable, but the [keratopathy] does regress.

Can dose modifications affect keratopathy events in this patient population?

Dose modifications can help, [including] lengthening the time between the treatments. The standard is 3 weeks, but if you go further than that, it tends to give the cornea time to resolve somewhat.

How does multidisciplinary management between oncologists and ophthalmologists play a role in monitoring these AEs?

[The management of corneal toxicity] is a great example of collaborating, working together, and making sure you have a great team. At the University of Maryland, we are lucky that we have such a coordinated care system. I have a clinic in the cancer center, so it makes it a much easier, integrated system for the patients. That is not standard at most institutions, but it is a great model for how closely ophthalmology and oncology should try to work together.

How involved should ophthalmologists be throughout the course of treatment? How frequent should those visits be to help manage AEs?

We see [patients] initially before they start the treatment. We see them at their baseline exam to find out if there are any underlying ophthalmic conditions and what their baseline vision is, so we can use that to monitor them as they move forward.

We need to see [patients] every 3 weeks if they’re on [belantamabmafodotin] or 4 to 6 weeks if they are on a longer regimen, but it tends to be every 3 weeks. The most challenging part is the scheduling because it can sometimes be hard to ensure that we can get [the visit] in exactly [at the 3-week mark] around the infusion schedule.

Is there anything else you would like to add about treatment-related keratopathy?

The biggest point I would like to emphasize is the collaboration between ophthalmology and oncology and how critical that is for patient care. [It is also important] to understand and educate the patients on [keratopathy]. Even if there is a vision change or corneal changes, we do have good options. [Keratopathy] is not a long-term toxicity, and we can stop treatment or increase lubrication [to mitigate it].