BCMA-Targeting Agents in the Treatment of Multiple Myeloma: Right Patient, Right Time - Episode 4
Natalie Callander, MD, presents the profile of a female patient with relapsed/refractory multiple myeloma who receives belantamab mafodotin and develops keratopathy.
Natalie Callander, MD: This case is a 61-year-old woman diagnosed with IgG kappa multiple myeloma in January of 2017 and judged to be revised ISS [International Staging System] stage II. Serum-free light kappa levels were 129 mg/L. The LDH [lactate dehydrogenase] was normal, as was the calcium. In this individual, there were no cytogenetic abnormalities noted, presumably that also means FISH [fluorescence in situ hybridization]. The patient had lytic bone lesions detected on a PET [positron emission tomography]–CT. Their past medical history is notable for diabetes, which has been controlled by medication. This patient was initially treated with bortezomib, lenalidomide, and dexamethasone induction, then underwent autologous stem cell transplant and has been receiving ixazomib maintenance.
Two years later, the patient developed progressive disease and had new lytic bone lesions, so this is more than just a biochemical progression. This is a clinical progression. At this point, the patient was treated with daratumumab with carfilzomib and dexamethasone. This lasted about 17 months, which is a good response, but then the patient went on to receive pomalidomide, cyclophosphamide, and dexamethasone. After 3 cycles, she had a PR [partial response] at best, but then progressed as well. She was then changed over to belantamab monotherapy. Five weeks after starting on treatment, the patient developed some dry eyes and vision changes. The belantamab had to be temporarily reduced, but the patient continues on belantamab with a response to treatment, and the ocular adverse effects have responded to the dose hold and a dose reduction.
This case is quite representative of patients who we’re seeing more in the clinic because it’s a person who had an initial induction with VRd [bortezomib, lenalidomide, dexamethasone] followed by a stem cell transplant. And in this case, she was on ixazomib maintenance, had a response for a while, and coming in next line in this particular incidence would be a CD38 antibody combination, which is very appropriate. But many patients have progression, and now you’re seeing a patient who’s looking at fourth-line therapy and had a very nice response to belantamab, but had some keratopathy.
One of the things that’s very gratifying with belantamab is that for the patients who are going to respond to it, we’ve tended to see that they’ll respond quite quickly. In other words, we’ll have a good idea within that 3-week dosing interval of whether they’re going to have a response. Once we’re pretty confident that that’s happening, you can focus on strategies to try to mitigate adverse effects. Now we have ophthalmologists who work with us in concert, so not only are we talking to patients about their eye symptoms, we also have our ophthalmologist telling us if they’re seeing any and whether we have to cut back or hold the drug.
One of the things that’s going to happen in the future is that we’re going to learn how to dose belantamab a little less frequently than every 3 weeks. This drug has a very long half-life compared with some of the other compounds. And what we tended to see in DREAMM-2—I’ve also seen this in my own practice—is that while you have a patient on a dose hold, as they’re improving their keratopathy, they don’t tend to progress with their myeloma, which is also a nice feature. I’m hoping that as we figure out how to dose this compound perhaps every 4 weeks, or maybe every 6 or even 8 weeks, particularly in combination with other drugs, that we’ll have fewer patients requiring dose holds for keratopathy.
Transcript edited for clarity.