ONCAlert | Upfront Therapy for mRCC

BCMA-Directed CAR T-Cell Therapy: Outlook

Targeted Oncology
Published Online:1:00 PM, Fri February 14, 2020

Nikhil C. Munshi, MD: Where do you see CAR T-cell treatment in 5 years? Do you think it’s going to be replacing some of our standard treatments? And then we can revisit the issue of how we are going to make it better because I think that’s important. But before that, do you envision that in 5 years, it is going to take over a lot of things we do?

Parameswaran Hari, MD, MRCP: Predictions are very difficult, but I am an optimist, as you are. I’m hoping that CAR T-cell therapy will quickly move into the early relapsed setting. And we need that, because triple-class induction is coming. So triple-class drug resistance is going to be more common in patients with earlier stages of myeloma. It will come there first, and I think it will quickly move into a space of especially high-risk disease, where it may be an induction, followed by CAR T-cell therapy, followed by some form of maintenance. CAR T-cell therapy is an immune technique that works irrespective of the clonal situation. We at least think so right now. In terms of responses, it surely is.

Nikhil C. Munshi, MD: Yeah, absolutely. And so, like you said earlier, to sort of sum up where we might go, we will use CAR T-cell therapy. We will use it so that the responses are sustained. So we will use it, maybe multiple times, or with some sort of maintenance treatment type of strategy. Maybe select CAR T cells, so on their own they will continue, and we can enrich them. There are ongoing thoughts that we may produce CAR T cells from immunized cells, so we can just vaccinate or give some immune stimulation to excite them.

And then are a lot of newer CAR T-cell products in development. One of the things you mentioned earlier was about allogeneic, off-the-shelf CAR T-cell therapies. And then there are CAR T cells with dual-targeting, 2 different antibody–targeting CAR T cells.

Parameswaran Hari, MD, MRCP: We have an abstract here.

Nikhil C. Munshi, MD: And there are also CAR T cells where you could inject an antibody to monitor its function, etcetera. And so I think there is a lot of enthusiasm and great prospect on the horizon regarding making myeloma a chronic disease or even curing the myeloma. Do you share the same thoughts?

Parameswaran Hari, MD, MRCP: I can now see where a majority of my patients are going to be MRD [minimal residual disease] negative fairly early in their disease course, before the clones have become advanced and evolved and multiple bad clones are present in the same patient. Before that situation, if we can make a lot of patients MRD negative, I think some of those patients may end up being cured. And we need to keep the MRD negativity sustained, as you very well know. Sustained MRD negativity is perhaps more important than 1-time MRD negativity.

Nikhil C. Munshi, MD: So with the new developments in BCMA-directed treatments, especially CAR T-cell therapy, I think we have a very enthusiastic outlook and a really optimistic future. It was great to discuss these various newer aspects with you. Thank you so very much.

Parameswaran Hari, MD, MRCP: Thank you so much, Dr Munshi.

Transcript edited for clarity.

Nikhil C. Munshi, MD: Where do you see CAR T-cell treatment in 5 years? Do you think it’s going to be replacing some of our standard treatments? And then we can revisit the issue of how we are going to make it better because I think that’s important. But before that, do you envision that in 5 years, it is going to take over a lot of things we do?

Parameswaran Hari, MD, MRCP: Predictions are very difficult, but I am an optimist, as you are. I’m hoping that CAR T-cell therapy will quickly move into the early relapsed setting. And we need that, because triple-class induction is coming. So triple-class drug resistance is going to be more common in patients with earlier stages of myeloma. It will come there first, and I think it will quickly move into a space of especially high-risk disease, where it may be an induction, followed by CAR T-cell therapy, followed by some form of maintenance. CAR T-cell therapy is an immune technique that works irrespective of the clonal situation. We at least think so right now. In terms of responses, it surely is.

Nikhil C. Munshi, MD: Yeah, absolutely. And so, like you said earlier, to sort of sum up where we might go, we will use CAR T-cell therapy. We will use it so that the responses are sustained. So we will use it, maybe multiple times, or with some sort of maintenance treatment type of strategy. Maybe select CAR T cells, so on their own they will continue, and we can enrich them. There are ongoing thoughts that we may produce CAR T cells from immunized cells, so we can just vaccinate or give some immune stimulation to excite them.

And then are a lot of newer CAR T-cell products in development. One of the things you mentioned earlier was about allogeneic, off-the-shelf CAR T-cell therapies. And then there are CAR T cells with dual-targeting, 2 different antibody–targeting CAR T cells.

Parameswaran Hari, MD, MRCP: We have an abstract here.

Nikhil C. Munshi, MD: And there are also CAR T cells where you could inject an antibody to monitor its function, etcetera. And so I think there is a lot of enthusiasm and great prospect on the horizon regarding making myeloma a chronic disease or even curing the myeloma. Do you share the same thoughts?

Parameswaran Hari, MD, MRCP: I can now see where a majority of my patients are going to be MRD [minimal residual disease] negative fairly early in their disease course, before the clones have become advanced and evolved and multiple bad clones are present in the same patient. Before that situation, if we can make a lot of patients MRD negative, I think some of those patients may end up being cured. And we need to keep the MRD negativity sustained, as you very well know. Sustained MRD negativity is perhaps more important than 1-time MRD negativity.

Nikhil C. Munshi, MD: So with the new developments in BCMA-directed treatments, especially CAR T-cell therapy, I think we have a very enthusiastic outlook and a really optimistic future. It was great to discuss these various newer aspects with you. Thank you so very much.

Parameswaran Hari, MD, MRCP: Thank you so much, Dr Munshi.

Transcript edited for clarity.
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