Single-Agent Belantamab Mafodotin for Triple-Class Refractory Multiple Myeloma

Suzanne Lentzsch, MD, PhD: Another interesting drug was recently approved. Data from the DREAMM-2 study showed that Blenrep [belantamab mafodotin], a CD38 antibody that’s coupled with a cytotoxic agent, is very effective in patients who are triple-class refractory. Response rates were around 30%. The drug was relatively well tolerated. Unfortunately, there is 1 main adverse effect, keratopathy, which occurs in about 50% of the patients. That can really limit the use of Blenrep, despite it being well tolerated and successful at inducing high response rates, because patients who experience grade 3 keratopathy have to stop and hold the treatment until they have improvement of the keratopathy. That can take several weeks. Interruptions of that treatment are very likely. Nevertheless, it’s very well tolerated. It’s an additional potent drug in our armamentarium for patients with relapsed/refractory multiple myeloma.

Peter Voorhees, MD: Another treatment option for patients with triple-class refractory disease is the antibody-drug conjugate belantamab mafodotin. This was the first FDA-approved BCMA-targeted therapeutic for these patients. BCMA is a cell surface receptor that’s unique to plasma cells. The way belantamab mafodotin works is that after infusion, it binds to BCMA-expressing plasma cells and, like any ordinary monoclonal antibody, can mediate antibody-dependent cellular cytotoxicity. In addition, just like brentuximab vedotin in Hodgkin lymphoma, the antibody-drug conjugate is taken up by the plasma cell, and the cytotoxic payload—which in this case is MMAF—is subsequently cleaved inside the myeloma cell, where it binds to microtubules and mediates cytotoxicity in that manner.

The DREAMM-2 study was a phase 2 trial that looked at 2 doses, 2.5 and 3.4 mg/kg of belantamab mafodotin infused once every 3 weeks, for patients with relapsed/refractory multiple myeloma. The vast majority of those patients had triple-class refractory disease. The study showed an overall response rate of 31%, with about half those patients achieving very good partial responses and complete responses. Importantly, the median duration of response was 11 months, which is very similar to the BCMA-targeted CAR [chimeric antigen receptor] T-cell therapy idecabtagene vicleucel, which was also recently FDA approved. Median overall survival for that study was 13.7 months. So belantamab mafodotin is another option.

In general, belantamab mafodotin is a well-tolerated agent. The rates of infusion reactions are quite low, despite the fact that a lot of patients did not get premedications prior to dosing in the phase 2 trial. We see some thrombocytopenia with this agent. But relative to a lot of the other therapeutics that we’ll use in this space, it’s very manageable. The most common toxicity associated with this agent is corneal toxicity. In the DREAMM-2 study, the rate of corneal events was around 70%. I tell patients that if they are going to get at least 2 doses or more and are responding to therapy, they are going to have corneal changes on physical exam at a minimum and may have symptoms related to that corneal involvement. That can include sensitivity to light, discomfort, and dryness in the eyes. In some cases, it can actually affect your vision, which can impact your ability to read, watch TV, and drive. For this reason, there’s a REMS [Risk Evaluation and Mitigation Strategies] program associated with this product. Patients need to be seen by an eye care specialist prior to each dose. It’s something that has to be monitored very carefully when you are administering this agent.

Transcript Edited for Clarity