BCMA-Targeting Agents in the Treatment of Multiple Myeloma: Right Patient, Right Time - Episode 3

Safety of Belantamab Mafodotin in Patients With RRMM

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Karen L. Klugo, MD, describes what’s unique in terms of patient response to belantamab mafodotin as treatment for relapsed/refractory multiple myeloma and risk of ocular disease.

Sagar Lonial, MD, FACP: I’m going to turn to Dr Klugo for a moment to ask a couple of questions about some of the unique adverse events that we see when patients receive belantamab mafodotin. Dr Klugo, what’s unique about belamaf [belantamab mafodotin] that you think ophthalmologists as well as oncologists need to be aware of? What are some of the strategies that you use to evaluate this?

Karen L. Klugo, MD: The patients who enrolled in the study were noted to have a significant amount of keratopathy. Of the 218 patients in the DREAMM-2 study, 77% of those were noted to have ocular adverse events, and the most significant was keratopathy. The medication creates epithelial microcysts that can only be seen under a slit lamp examination. It’s important for patients to be under the care of an eye care professional while receiving treatment, and that the oncologist and eye care professional work together and have a good line of communication to be able to watch these patients and look for any signs of adverse events. The keratopathy is the most significant; 76% of those patients had keratopathy. In the study, 55% of the patients had visual acuity changes, 27% had blurred vision, and 19% had dry eye. These patients need to be monitored in conjunction with the oncologist and eye care professional.

Sagar Lonial, MD, FACP: To follow up on that a little, are there patients who can have keratopathy without symptoms? If so, how would you explain that in terms of the mechanism of the spread of the keratopathy across the cornea?

Karen L. Klugo, MD: Those patients can definitely have keratopathy. It’s recommended that they see the eye care professional 3 weeks prior to having their initial dose. Because the dosing is every 3 weeks, it’s recommended to have their follow-up within a week after their dose and within 2 weeks before their next dose to look for these changes, these epithelial microcysts. In the study, most of the keratopathy developed within the first 2 treatment cycles. In my experience, I was able to see these epithelial microcysts before the patients became symptomatic.

The mechanism isn’t exactly known, but the corneal epithelial cells are formed in the limbus, which is the junction between the cornea and conjunctiva. As this medication must get into the limbus, it spreads from an outward to inward type of mechanism. The further it gets toward the central cornea, the more it will affect the visual acuity, because we’re more likely to use our central cornea than our peripheral cornea. As these patients get into their repetitive doses, their epithelial microcysts become more evident and prominent in a lot of situations.

Sagar Lonial, MD, FACP: That’s an interesting finding. I’m curious about your view here, because we’ve certainly had our share of patients, and you may have as well, where they didn’t have symptoms or changes in vision, but they had what looks like grade 2 keratopathy and over time developed some blurred vision, but the blurred vision seemed to resolve much faster than the grading of the keratopathy. That might have to do with that central vs peripheral impact and where it starts and where it begins to recede.

Karen L. Klugo, MD: It’s important to mention that there’s a KVA [keratopathy and visual acuity] scale that’s provided by GSK [GlaxoSmithKline], and that’s how I can communicate with the oncologist to rate the amount of corneal findings. It goes from normal to grade 4. With normal, there are no changes. In grade 1, a mild superficial keratopathy is present with a decline of 1 line of Snellen visual acuity, so 1 line on a chart. Grade 2 goes up to moderate with 2 to 3 lines. Grade 3 is a severe superficial keratopathy with 3 lines, but better than 20/200 vision. And grade 4 is corneal epithelial defect and vision worse than 20/200.

If these patients get to grade 2 keratopathy, a moderate keratopathy, that’s when we need to communicate together and decide what the risk-benefit is for these patients and whether their dosage should be stopped or halted or resumed at a lower dose. I’ve seen a little of everything. In every situation, if the patients had a grade 2 keratopathy, they were symptomatic. In my experience, patients who weren’t responding to treatment on the oncologist end also weren’t developing the keratopathy. I don’t know that I’ve seen that written anywhere, but I probably had 2 or 3 patients who ended up off of treatment because they weren’t responding, and they also had no corneal findings.

Sagar Lonial, MD, FACP: That’s interesting. I hadn’t seen that anecdote. That’s very helpful to know as well.

Transcript edited for clarity.