Part 2: Choosing Between BCMA and CAR T-Cell Therapy in Multiple Myeloma

Natalie Callander, MD (Moderator)

Professor, Hematology/Oncology

University of Wisconsin-Madison School of Medicine and Public Health

Madison, Wisconsin

DISCUSSION QUESTION:

• Have you used belantamab mafodotin (Blenrep)? If so, what was your experience?

NATALIE CALLANDER, MD: If you haven’t used belantamab, what reservations do you have about it, or any difficulties [in accessing it]?

ROBERTO MONTOYA, MD: None of my patients have reached the point of resorting to these kinds of therapies. We have belantamab and the chimeric antigen receptor [CAR] T-cell therapy. There [are no studies] comparing between them. Is there any logic to picking one over the other?

CALLANDER: We were fortunate to have belantamab in trials a number of years ago, and I think that the best thing about it is it’s just available. The patients who respond to it seem to respond quite well and quite fast. We have had patients who were burning through [other treatments], and then they had 1 or 2 doses of belantamab and had a significant improvement in their myeloma.

The biggest issue with CAR T cells is it takes a while to get those cells manufactured, so you have to have a patient who’s stable enough so that you can harvest or phorese those T cells, and then they have to be manufactured. If you [start seeing] a patient who is on steroids or has just had a drug like bendamustine for their myeloma, that patient may have very poor lymphocyte counts, collecting cells to even manufacture the CAR T cells is quite difficult.

Even if you get over that hurdle, and you get the CAR T cells collected, it takes 4 to 6 weeks to have the cells manufactured for that patient. Then the patient must stay in some reasonable shape. They don’t need to go into remission, but you have make sure that they don’t start having kidney problems, or other problems. For some of these patients, that is really difficult.

One of the biggest advantages of belantamab is that it has a different mechanism of action. I have used belantamab first for unstable patients. Another fortunate thing is that we have some ophthalmologists on site because we had studies going on, and the Risk Evaluation and Mitigation Strategy program.

There are reports of patients who have relapsed post–CAR T-cell therapy getting belantamab and responding to that, which I think points [to using] the BCMA [B-cell maturation antigen] therapies that we have, and the ones that are coming.

I don’t think we know how to sequence [these later-line options], if there’s something that would be bad to do, or deleterious to do. I don’t believe that if you have belantamab before trying to go to CAR T-cell therapy, that it is going to spoil it, but getting it through a clinical trial often prevent us from giving any other BCMA-directed therapy. Now that the commercial CAR T-cell therapy is available, I think we will soon figure out whether there are types of patients who don’t do well with CAR T-cell therapy based on what treatments they’ve had before.

SAURABH CHHABRA, MD: I agree with you completely. In my limited experience, I’ve given belantamab to 5 or 6 patients, and I’ve seen responses in roughly half of the patients. But my problem has been that none of my patients were able to get more than 2 doses, because after 2 doses, either they progressed, or they developed grade 2 keratopathy or other conditions. We had to hold treatment, and while they waited, either there was concern that they would progress even if there was no objective evidence of it, or they did progress and they had to go on to another treatment.

It is tough to choose between belantamab and CAR T-cell therapy. The data look good with CAR T cell, but it’s hard to get to CAR T cells at this point, whether from clinical trials or commercially. It’s hard to use belantamab before CAR T cell from a clinical trial perspective, but I think I probably wouldn’t hesitate using belantamab even as a bridging therapy after the patients went through apherisis, before they go on to commercial CAR T-cell therapy. Right now, we can’t do commercial CART cell because we just don’t have slots.

CALLANDER: I would agree with all that.

MONTOYA: I have another question about the real-world data. You have these 2 drugs that you can use in the same patient scenario, but in the real world, which one of them easier to get authorized or approved to start on the patient?

CALLANDER: What more and more of us are saying is that if you think you might have a patient for CAR T-cell therapy, the way things are going right now, it would be good to have them seen by a center than can deliver CAR T cells, because the waiting times are long. What we can’t do, and I think Dr Chhabra will agree with this, is call a treatment center and say that you want them to have CAR T-cell therapy in a week. It’s not going to happen. Unfortunately, it will be months before they will be able to have cells collected, let alone manufactured. So, it’s a tough situation if you want CAR T cells. And, as Dr Chhabra said, the clinical trials that are accruing right now are limited, and the access to the commercial CAR T cells is limited.