Role of Belantamab Mafodotin in R/R MM

Nina Shah, MD: Sagar, you know these data really well. Give us an overview of the mechanism of action of belantamab mafodotin, and maybe talk about the DREAMM-2 study design and the FDA approval and what the implications are for the clinical practice, knowing that we have this as an available option.

Sagar Lonial, MD, FACP: Belantamab mafodotin was approved by the FDA based on the DREAMM-2 study, which was a randomized trial of 2.5 mg/kg, which is the FDA-approved dose with 3.4 mg/m2. That was the recommended phase 2 dose [RP2D] from the DREAMM-1 study. It was trying to look at the RP2D vs what the FDA thought was a kinder, gentler dose based on some preliminary data as well. It turned out that the lower dose allowed patients to stay on treatment longer and resulted in about a 30% response rate and a median DOR [duration of response] of about 11 months. To put 11 months into perspective, when we talk about drugs like carfilzomib, which was approved on accelerated approval with a similar phase 2 design, the carfilzomib DOR was between 9 and 10 months. Daratumumab was about 10 months. All had 30% response rates, so it’s certainly in line with many of the “backbone drugs” we have in myeloma.

The most common adverse events we see are keratopathy or microcysts in the cornea. Those tend to start at the periphery and work their way inward. They don’t necessarily impact visual acuity until they become grade 3 or higher. It can be viewed by a slit lamp relatively easily. If you look at the DREAMM-2 study, while 70% of patients had some form of keratopathy, only 50% had symptomatic keratopathy and only 3 had to come off because of adverse events related to keratopathy. It can be managed with a partnership with an ophthalmologist. That’s probably the hardest part of giving it, finding that ophthalmologist or optometrist whom you can work with, and making sure they can get them in to see the patient when you need them to see the patient to make decisions about treatment.

Nina Shah, MD: Thanks for that overview. There are a lot of nuances to this, and we get so excited about these high response rates, but it’s important to know that the benchmark was 30%. Those are important data for us to look at, as well as the duration of response. Katja, you talked about how you don’t have access to this drug, but thinking into the future when you do, do you think belantamab mafodotin has the opportunity to move into the earlier relapsed setting, not just waiting for 4 lines or 4 treatments? Do you think it could be used earlier?

Katja Weisel, MD: Absolutely. The studies are on the way, including the DREAMM-3 trial, with the randomized comparison of belantamab mafodotin as a monotherapy to pomalidomide-dexamethasone from first relapse. Then we have DREAMM-8 with belantamab mafodotin in combination with pomalidomide and dexamethasone vs PVd [pomalidomide, bortezomib, dexamethasone] from first relapse. There are clearly those clinical trials assessing that, and we’re always a bit conservative waiting for the evidence generated, but we’ll have it very soon.

Transcript Edited for Clarity