BCMA-Targeting Belantamab Mafodotin: Role in the Treatment Landscape of RRMM

Sagar Lonial, MD, FACP: We know that belantamab mafodotin, or belamaf, is an antibody-drug conjugate. The antibody portion targets BCMA on the surface of plasma cells, and it brings in an immunotoxin known as MMAF [monomethyl auristatin F]. An MMAF is basically a cousin of a vinca alkaloid and has the ability, when directly targeted to the cell and then internalized, to kill the cell through DNA damage–type mechanisms.

The FDA-approved study that led to the approval of belamaf [belantamab mafodotin] was a randomized phase 2 study called DREAMM 2. The DREAMM 2 study evaluated 2 different doses of belantamab mafodotin: 2.5 and 3.4 mg/kg. It should be noted that the 3.4 mg/kg was the recommended phase 2 dose, but there were concerns about some unique adverse events that we’ll talk about in a few moments. The FDA requested that a lower dose be tested as well as part of a randomized trial.

There were close to 200 patients randomized between those 2 doses of belamaf, with a median of 6 to 7 prior lines of therapy. It was noted that while the response rate was similar between the 2 arms—about 30%—and the depth of response was similar with similar rates of VGPR [very good partial response] or better, the DOR [duration of response] among responders appeared to be better with the lower dose, likely associated with less severity of some of the unique ocular adverse events that we’re going to talk about in a moment. That ultimately led to the FDA approval of belamaf [belantamab mafodotin] at 2.5 mg/kg.

The potential importance of this study is that in a group of patients who are triple-class refractory, this offers them significant benefit because there are few, if any, treatments available for triple-class refractory myeloma. More important, this represents an off-the-shelf treatment approach. This is important because it potentially offers the ability to get new treatments, particularly treatments that target BCMA when a patient may be noted to have highly resistant or even refractory multiple myeloma.

As belamaf [belantamab mafodotin] has been used more of late, there are studies beginning to combine it with commonly used agents, such as bortezomib and pomalidomide. In fact, these are beginning to bring the use of belamaf into earlier lines of therapy and are being tested in randomized clinical trials. But whether they’re available for first or second relapse is being studied in a number of studies in the DREAMM series that will help us better evaluate how to best use belamaf [belantamab mafodotin] in the context of relapsed multiple myeloma.

Transcript edited for clarity.