Belantamab Mafodotin–Induced Keratopathy Remains Manageable in Multiple Myeloma

The utilization of belantamab mafodotin-blmf (Blenrep) in multiple myeloma can be associated with unique adverse effects (AEs), including keratopathy and dry eyes. However, with proper management, these AEs can be both manageable and reversible, according to Malin Hultcrantz, MD, PhD.

“There are a lot trials ongoing to see what can be done to mitigate side effects,” Hultcrantz said. “There are trials with lower dosing and with longer dose intervals. Also different combinations of both approved and investigational drugs to see if we can potentiate the drug to keep the high efficacy, but also reduce the [adverse] effects in terms of the keratopathy.”

In an interview with OncLive^®, Hultcrantz, a hematologic oncologist at Memorial Sloan Kettering Cancer Center, discussed the efficacy of belantamab mafodotin, as well as standard management for common AEs associated with the treatment.

OncLive^®: What are the differences between mild-to-moderate and severe keratopathy associated with belantamab mafodotin in patients with multiple myeloma?

Hultcrantz: The difference between the grades of keratopathy in patients treated with belantamab mafodotin is based on the Keratopathy Visual Acuity (KVA) scale, which has 2 parts. One part is what is found on the ocular exam, and it has to do with the grade of keratopathy, where grade 1 or mild keratopathy is usually if [patients] have a superficial punctate keratopathy, and [grade 1 or mild] is sometimes associated with these microcysts that can also be seen.

Grade 2 is called moderate, and there you see a higher grade, often with the microcysts. But, they're still located toward the periphery. It [also] has to do with a density of these changes. Grade 3 or 4 would [have] more of a central impact on the eye, and they tend to be a higher density of these changes and also be confluent.

Then we also have the second part, which is the visual acuity, where the best visual acuity is graded. Grade 1 is if you have a decrease in 1 line of visual acuity, whereas grade 2 is 2 or 3 lines. Grade 3 is more than 3 lines of decrease in visual acuity.

What are some best practices for managing this potential AE?

[Clinicians] must have a good collaboration with their ophthalmologist, whether you’re at a bigger hospital and you have your own ophthalmology team, or if you’re in a smaller practice, you can have a designated ophthalmologist.

Because these are specific changes, and [with] the way the drug is approved and the way the trials are run, patients need to have an ocular exam prior to each dose. You need to have good collaboration with an ophthalmologist and have that [conversation] if there are any changes that would then lead to dose modifications or dose delays.

Can you expand on dose modifications for these patient populations? How frequently do you alter doses?

It happens pretty often. [If they have grade 2 or higher changes], the first thing we’ll do is pause and wait. Most of these changes are reversible, so [patients] need to go back to grade 1 before we continue dosing. If they have grade 1 only, you can continue the dosing as is. If they have grade 2 or more, the dose will be delayed, and then wait until it goes back to grade 1. [Another] step is to do a dose modification to decrease the dose.

How early should the ophthalmologist get involved? How often are visits happening between the patient and the ophthalmologist?

If you’re thinking of starting any patient on this, it's good to have an ophthalmologist on board because they need to see the patient often. They need to go through specific training, because there are specific criteria if you can continue the drug or not, and specific forms to fill out, so it’s good to have [ophthalmologists] on board early.

Patients need to see the ophthalmologist before starting to get a baseline. Then, the standard dosing is every 3 weeks. They just need to see the ophthalmologist before each dose. If there are dose delays, it would be maybe every 3 to 6 weeks, but every 3 weeks is the regular interval. We usually have the ophthalmology visit days before the patients see the clinician and get the dose, so you have that time to react in case you need to hold the dose or do any dose modifications.

Can you speak to outcomes of the adverse effects of belantamab mafodotin?

In a phase 2 trial with the single-agent drug belantamab mafodotin, the more common [toxicity] is keratopathy. The patient's symptoms would then be dry eyes and blurry vision. Blurry vision is a little bit less common, but around 56% of patients had experienced that [adverse] effect.

The important thing to say is that almost all of them are reversible. Therefore, if you just hold the dose and wait, most patients will go back to a normal cornea. This is very important for patients, but it can take up to 3 or more months. Therefore, you should have patience, but you can reassure [patients[ that this will go back [to normal].

What does the future of this treatment look like?

Looking forward, there are a lot trials ongoing to see what can be done to mitigate side effects. There are trials done with lower dosing and with longer dose intervals. There are also different combinations [with belantamab mafodotin being investigated to] see if we can potentiate the drug to keep the high efficacy, but also reduce the [adverse] effects in terms of the keratopathy.

[Moreover], the ocular toxicity from belantamab mafodotin doesn't come from the BCMA part of the drug. It comes from the drug that the antibody is conjugated with, so that drug is called monomethyl auristatin phenylalanine [MMAF]. This conjugate is also used with other antibodies and other diseases. The same ocular toxicity is seen there, so this is not seen with other BCMA-targeted therapies.