Shaji Kumar Discusses the First Approved Anti-BCMA Therapy

Shaji Kumar, MD, consultant in the Division of Hematology and professor of medicine at Mayo Clinic Cancer Center in Rochester, Minnesota, discusses B-cell maturation antigen (BCMA) as a target for multiple myeloma and the first U.S. Food and Drug Administration-approved anti-BCMA therapy, belantamab mafodotin.

In part two of this interview with Dr. Kumar, he discusses results of the ENDURANCE trial.

Dr. Kumar, the first anti-BCMA therapy was recently approved for relapsed/refractory multiple myeloma. Why is this a target of interest for multiple myeloma?

Dr. Kumar: I think the BCMA, in general, the immunotherapy, all of them seems to be quite effective based on the initial data. BCMA, or the B-cell maturation antigen, is a target that has not been used from the therapeutic intent up until now. The good thing about BCMA is it is present on all myeloma cells and does not really seem to change much over the disease course, suggesting that this could be an antigen that could be targeted multiple times along the course of the disease evolution. One is the expression part of it, and it seems to be relatively limited to the B-cell lineage. So the toxicity outside of those cells might be limited, especially when you’re using the other immunotherapy approaches that are different from the belantamab that was just approved. And obviously the patients, at this point, very few patients, if any, have seen any therapy that’s targeted to BCMA. So it’ll definitely be a new kind of treatment naïve for most of patients.

What were your thoughts on the study data from the DREAMM-2 trial for which the FDA approval was based?

Dr. Kumar: The DREAMM-2 was essentially a large phase two study. And it is compared to what historically we would have anticipated from those patient populations. It’s a heavily pre-treated group of patients. Most of the patients had five to six prior lines of therapy. A majority of the patients had seen the currently available agents. They looked at two different drug doses in that study. Both of them had a nearly equal number of patients. The efficacy seemed to be quite comparable, but I think from a toxicity perspective, the lower dose appeared to be better tolerated. And that is what is moved forward and is currently on the label, which is the 2.5 mg/kg. They did have a little over 30% response rate in this heavily pre-treated patient population. The overall progression-free survival wasn’t very long, but in patients who did get a response, the duration of response was close to a year.

It’s clear that people who respond to the therapy have durable responses. Now, obviously a significant proportion of patients did not respond. And those patients, some of them did have stable disease, which can be quite meaningful in this late stage of the disease. But for the people who did not respond, the big question is going to be, can we get some benefit from this therapy by maybe combining it with other drugs? And of course, from an overall disease outlook, this also suggests that maybe we do need to move that earlier on in the treatment of these patients. They might be able to see more of a benefit from those.

I think the biggest issue that we find from the trial and that has implications for practice is the ocular toxicity. Even though only a third of the patients had eye symptoms, nearly two-thirds of them had some findings in their eye, which is the basis for the current REMS program that goes with the drug, which does mandate that patients do have an eye exam before they receive each dose. And based on the toxicity pattern, we have seen and how patients did on the DREAMM-2 study, there’s a good possibility that maybe we don’t need to give the drug every three weeks, but maybe based on what we are seeing with the eye symptoms, it might get delayed up to six weeks between each dose, and still we may be able to retain the benefit.

Which patients do you think or do you recommend to be the most appropriate to receive an anti-BCMA therapy?

Dr. Kumar: Right now, obviously, other than the belantamab, we cannot use any of the other anti-BCMA therapies in the clinic, because nothing else has been approved. And for the belantamab, I think we are going to be, literally at this point, sticking with the label, which means many of these patients are going to be later-staged patients. Obviously, in the context of clinical trials, hopefully we can start treating some of these patients much earlier on so that we can potentially figure out how best to use this class of drug.