COMMENTARY

Lymphoma Takeaways From ASH 2015: CAR T Cells and Immunotherapy

Ann S. LaCasce, MD, MSc

Disclosures

December 17, 2015

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There have been some great advances presented at the 57th American Society of Hematology (ASH) Annual Meeting, particularly with regard to immunotherapy. The first group of very compelling abstracts were the CAR T-cell studies that were presented by the group from the University of Pennsylvania[1] and from Seattle,[2] the group at the Fred Hutchinson Cancer Research Center, who talked about their experience with CAR T cells in diffuse large B-cell lymphoma. They saw remarkable responses in patients who had been very heavily pretreated: 50% response rates. The toxicity is not trivial, and there is a lot of ongoing effort to understand how to mitigate that and what factors can predict that. I think the Seattle group did a very nice job of presenting their technology and how they're giving back equal numbers of CD4+ and CD8+ T cells, which I think is something we haven't heard about before, and how that affects the durability of the product and the responses. Understanding the biology of that is very fascinating.

In addition, there was some preliminary information[3] looking at CD30+ CAR T cells, which is brand new in Hodgkin disease and other CD30+ lymphomas. Although it was very preliminary, it looked interesting. They didn't give any prior chemotherapy before giving the CAR T cells, and the toxicity was very minimal in that study. We'll need to see how that plays out.

There was also a very, very interesting study[4] that was presented looking at generating T cells against multiple different antigens in tumor cells—five different antigens. This was worked on by the group at Baylor College of Medicine. They gave those back in a sequential way, with the ultimate goal of giving all of these T cells and targeting five different tumor antigens simultaneously. When they gave the single T cell-directed product, they saw a spread of antigens and responses beyond what they would have [previously] seen. I think that's going to probably launch a whole new line of investigations of that type of approach.

We also just saw the follow-up in Hodgkin disease that looked at immunotherapy. It showed that the responses are quite durable. With nivolumab[5] and pembrolizumab[6] in Hodgkin disease with very refractory patients, people are still doing well, with the median progression-free survival not met yet in the nivolumab study. I think now we'll start to see some combinations. There was an early study[7] combining brentuximab and ipilimumab that looked very interesting with very good responses and tolerability. I think it was quite impressive.

A couple of new drugs are also coming along in diffuse large B-cell lymphoma. The EZH2 inhibitor looked very promising. We'll have to see. It's not clear that only the mutated patients respond, so we'll need to try to understand that a little bit better.

Overall, the meeting for lymphoma has been very exciting, and we look forward to seeing some more information about how CAR T cells are going to play out and the durability of those responses. The same is true in immunotherapy.

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