COMMENTARY

Takeaways From ASH 2015: Developments in CAR T-Cell Therapy

Miguel-Angel Perales, MD

Disclosures

December 22, 2015

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I am Dr Miguel-Angel Perales. Let's talk about what we learned at the American Society of Hematology (ASH) annual meeting this year regarding CAR (chimeric antigen receptor) T cells. Again this year, like other years, there has been a lot of buzz about CAR T cells. This year we have seen CAR T-cell studies in myeloma, lymphoma, and leukemia as well as in other diseases, such as Hodgkin lymphoma. We saw some data presented already Friday at the Bone Marrow Transplant Winter Workshop. We had a whole scientific session that was held at the meeting, and then we had several abstracts presented as well as posters.

What is the take-home [message] from this year's ASH meeting in terms of CAR T cells? I think the field is starting to mature. We are starting to see more long-term, follow-up data. Of note, in some of the ALL (acute lymphoblastic leukemia) studies, obviously the data are the most promising, with results on the order of 80%-90% response rates.[1] We are starting to see that patients potentially may be cured with this therapy. It's really important for us to understand that this may be a therapy that actually can cure patients and not just put them in remission so they can go to transplant.

Obviously we are going to need a lot of data to understand which patients are potentially cured, what the prognostic factors are for that to occur, and what the percentage of cure rates is. Kite Pharma got breakthrough designation [December 7] for CAR T cells in lymphoma, and Novartis and Juno already have breakthrough designations in leukemia. We heard the story before ASH of the patient in London treated with off-the-shelf CAR T cells based on the TALEN® technology that was developed by Cellectis.[2] That was very interesting in terms of conceptual development; Cellectis is actively accruing patients currently in the United Kingdom.

So the take-home message for me is that the field is maturing, and we're starting to see more long-term follow-up. There were also several studies that showed new data. I think myeloma is something that is resonating. There was a study not of CAR T cells but of NY-ESO-1 TCR-engineered T cells that was published in Nature Medicine[3] earlier this year by Aaron Rapoport, from University of Maryland, that showed very nice data in patients with myeloma receiving T-cell receptor-modified T cells against NY-ESO-1, which is expressed in myeloma. Those data were quite impressive. One of the limitations of TCR is obviously HLA restriction. Carl June has published some work with CD19 CAR T cells and myeloma.[4] We will have to see how far that goes based on the American Society of Clinical Oncology (ASCO) data, which I think were not as promising as the NY-ESO-1 TCR data.

But there are other targets in myeloma. We saw some data[5] here already against B-cell maturation antigen (BCMA), and I am sure there are other targets in development; I know that my colleagues at Memorial Sloan Kettering Cancer Center are developing other targets for myeloma. I'm looking forward to next year's ASH meeting to see what's going on in CAR T cells. At that stage, I think we are going to start seeing some of the phase 2 registration studies start to mature, and most of us expect that in the next 12-18 months, one or more of these products will be on the market, and we will start to get into other diseases, other indications, and other antigen targets.

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