BCMA-Targeting Agents in the Treatment of Multiple Myeloma: Right Patient, Right Time - Episode 6
What to know in terms of dosing belantamab mafodotin treatment in patients with relapsed/refractory multiple myeloma.
Sagar Lonial, MD, FACP: I’ve had cases where I treated patients and they developed keratopathy that required me to hold a dose, it resolves or completely goes away, then I retreat them, and then it’s back in a cycle or two. Then I hold again and it goes away. Have you seen that pattern? One of the questions that patients often ask me is whether there are cumulative issues with this over time. My sense is that there aren’t, but I’m curious about what you think about that.
Karen L. Klugo, MD: I don’t know about cumulative over time. My experience is somewhat limited because the drug has only been around for so long. But anytime somebody discontinued the treatment, the microcyst would go away. That would maybe happen by the next time I saw them, or occasionally it was a couple of months later. In the circumstance with the patient with cataracts, it took close to 4 or 5 months for her keratopathy to resolve, but ultimately it did go away. With the oncologist I worked with, the patients who had significant keratopathy had reduced doses on subsequent treatments. If they had visually significant changes repeatedly, they ultimately discontinued therapy altogether.
Sagar Lonial, MD, FACP: That’s another important point. Certainly, in many of my patients, when we saw that pattern of giving a dose or two and then holding and repeat, there were 2 things I had to do. The first is to reassure patients, because often they think if they’re missing a dose, that their cancer is going to grow back. If you look at patients who had to have their dose held, a majority of them either stayed stable or deepened their response during that period. It hearkens back to the comment you made earlier. Patients who don’t respond don’t seem to get keratopathy, whereas patients who do respond may seem to get keratopathy. It may be that the half-life of the antibody is so much longer that while you’re waiting for the keratopathy to resolve, they don’t lose disease control. About 85% didn’t lose disease control, even with holds of 2, 3, and 4 cycles of treatment. That’s 12-plus weeks of treatment holding.
Karen L. Klugo, MD: That was exactly my experience as well. They’d be worried that I’m holding, but then they’d come back and I’d ask, “How is your laboratory work? How are things looking?” And they would say, “I’m fine. The doctor says I’m doing great. I’m holding steady.” I would say, “OK, your corneas are doing the same thing.” There’s something to be said about using that as a window to seeing where the treatment is. Then as the microcysts start to fade, their response to treatment is probably doing the same as well.
Sagar Lonial, MD, FACP: Yes. The other thing that we’ve learned in a few of our patients who have had that on and off schedule is that we’ve switched them to an every-6-week dosing cycle. By doing that, we’re able to not get severe keratopathy that becomes symptomatic or requires dose holding. But at the same time, the half-life of the antibody in those patients who get it every 6 weeks seems to be perfect. I’ve had a couple of patients for 2 years getting dosed every 6 weeks. With an alternative dose, the patient may guide you on what the right dosing schedule is for them. That makes it important.
Karen L. Klugo, MD: Do you think there’s any difference between your male and female patients or with the size of the patient?
Sagar Lonial, MD, FACP: I don’t know that I’ve noticed that. It’s mg/kg, so it should be dosed by size. But I haven’t noticed a male/female difference. I’m curious, have you?
Karen L. Klugo, MD: No. I don’t know that my number of patients is high enough to say, but I feel like the patients who had more significant keratopathy seemed to be female.
Sagar Lonial, MD, FACP: Interesting.
Karen L. Klugo, MD: But maybe that’s just an anecdotal thing.
Sagar Lonial, MD, FACP: That’s interesting. We’ve probably treated around 30 to 40 folks, but I don’t know that we’ve looked specifically at that. An interesting sidebar is that in general, with pretty much any treatment, women seem to do better than men—at least in myeloma—even though it’s slightly more common in men than in women. Maybe it has to do with more adverse events limiting dose intensity. I’m not sure. It’s interesting.
Transcript edited for clarity.