Managing Toxicities of Belantamab Mafodotin


A key opinion leader in medical oncology reviews optical and hematological toxicities of belantamab mafodotin and discusses how to mitigate adverse events.

Sagar Lonial, MD, FACP: When we think about the safety or adverse-event profile associated with belantamab mafodotin, there are 2 things to talk about. The first is keratopathy. Keratopathy is a way to describe the microcysts that develop in the cornea as a consequence of MMAF, which is the immunotoxin associated with belantamab mafodotin. Microcysts can develop, and many patients may be asymptomatic or low symptomatic.

If you look at the 72% of patients who developed keratopathy of all grades—grade 1, 2, 3, or 4—it is important to recognize that most patients had either asymptomatic keratopathy, or they had dry eyes or itchy eyes as their most common symptom. This is important because, while keratopathy in the current criteria is based on an ophthalmologic exam, it does not always translate into clinical impact. The reason I say that is because, in the 2.5-mg/kg dose arm of the DREAMM 2 trial, only 18% of patients had changes in visual acuity that required significant dose holds or dose modifications. Most patients ended up with grade 1 or 2 keratopathy, which did not require significant intervention other than perhaps holding if the severity of the dry eyes was significant.

In the DREAMM 2 trial, we also tested the use of steroid eye drops in a randomized fashion to see whether that could reduce the incidence or severity of keratopathy. What we learned in that randomized substudy was that steroid eye drops did not offer any significant benefit, so the recommendation is to focus on lubricating eye drops applied every few hours to make sure you mitigate some of that dry-eyes issue that can occur with keratopathy.

The other big category of adverse events that comes about is hematologic toxicity. That did occur, but it was to a much lower degree than keratopathy, with neutropenia and thrombocytopenia being the most commonly seen. Most of that was grade 1 and 2, despite that this was a heavily pretreated refractory myeloma by patient population.

The main adverse events of interest are focusing on keratopathy. The best way to try to mitigate or manage this is lubricating eye drops, as I mentioned before, as well as the use of a partnership with ophthalmologists or optometrists. The reason this becomes important is that they may pick up a significant microcyst or a keratopathy issue that is not symptomatic, so it is important that they see the ophthalmologist before every dose of belantamab mafodotin is administered. That then allows you to take their exam findings into account when you make a decision using the REMS [Risk Evaluation and Mitigation Strategies] program about whether to dose that patient on that day.

It is important to recognize that skipping a dose or even skipping 2 doses did not necessarily have a significant adverse effect on the long-term outcome for patients. In fact, if you look at most patients who had to miss 1 or more doses of belantamab mafodotin, a majority of them—well over 80%—had stabilization of their disease or deepening of their response as opposed to progression, which is typically what we will see with other agents when we have to skip a dose or miss a dose. Missing a dose or skipping a dose is safe, is acceptable, and allows patients with keratopathy to reduce it to a lower grade so you can treat them with the same dose or a dose reduction, depending on the severity of their keratopathy.

Transcript edited for clarity.

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