Press "Enter" to skip to content

ASH Expert NHL Roundtable: Episode 3

At the recent American Society of Hematology meeting in Orlando, John Sweetenham, MD, of the University of Texas Southwestern Medical Center in Dallas, Mitchell Smith, MD, PhD, of the GW Cancer Center in Washington, D.C., and Michael E. Williams, MD, of the University of Virginia in Charlottesville, gathered to discuss new and some potentially practice-changing data from the meeting in the field of B-cell lymphoma, both aggressive and indolent B-cell lymphoma.

In this third of three exclusive MedPage Today episodes, the discussion centers on chimeric antigen receptor (CAR) T-cell therapy and advances in CAR T-cells.

Episode 1: PET-Directed Therapy for Early-Stage Aggressive non-Hodgkin’s Lymphoma

Episode 2: Relapse and Refractory B-cell Lymphomas

Following is a transcript of their remarks:

John Sweetenham: Hello and welcome to our expert panel at ASH 2019. My name is John Sweetenham from UT-Southwestern Harold Simmons Comprehensive Cancer Center, and I am joined today by Dr. Mike Williams from the University of Virginia and Dr. Mitchell Smith from George Washington University. We’re here to talk about some of the latest findings which have been presented at ASH in the field of B-cell lymphoma, both aggressive and indolent B-cell lymphoma. Welcome, and Mike and Mitchell, thanks for being here. It would be impossible to come to ASH in 2019 and talk about relapsed and refractory large B-cell lymphoma without talking about CAR T-cell therapy and advances in CAR T-cells. Of course, there are many, many abstracts this year. But in particular, there’s a new study of liso-cel [lisocabtagene maraleucel], one of the newer CAR T-cell products. This, again, looks as if it’s showing some promising activity. Mike?

Michael Williams: Right, it was a larger series of patients that was presented, and I think some of the encouraging aspects of this particular agent is that it seemed to be at least as well, if not somewhat better, tolerated and that outpatient administration was a possibility in a significant number of the patients. So having a product that is showing good activity perhaps with a more manageable toxicity profile is, I think, of certainly relevance and importance to this group of patients.

Sweetenham: Mitchell, they were presenting some kind of extended follow-up from the original study, and it looks as if the activity is somewhat comparable to the other CAR T-cell products that are already out there. Do you think that’s fair?

Mitchell Smith: I think that’s a fair statement. Obviously, they’re not compared head-to-head and there’s details in the patient populations, but overall, I think they all settle in at that 30% to 40% sort of plateau that we hope will mean that these are long-term survivors, but we don’t know yet, even with the data on the more mature ones. I think efficacy-wise there’s probably not a lot to play with, but the toxicity, as Mike mentioned, seemed to be easier — more outpatient even a possibility. It tends to vary, it seems, with the co-stimulatory factor that’s in the preparations, but there are details in the preparation of the cells and apheresis procedures and expansion. I was struck by the number of patients who were entered in the study who did not end up getting the cells returned, and that’s a bit of a concern. As we go forward, we want to be sure that we can actually deliver these cells to the patients.

Sweetenham: This is probably an impossible question, but I’ll ask you both to speculate on it anyway: In, let’s say, a year or 2 from now, where do you think we’ll be in terms of the use of CAR T-cell therapy in relapsed and refractory B-cell lymphomas? What do you see ahead? I guess we’ll probably have some early results from the ZUMA-7 trial by then. Don’t know quite when they’re expected, but how do you see it playing out, or how should it play out, over the next year or 2?

Williams: I think ZUMA-7 will be an important study since it compared a CAR T with sort of traditional, second-line or so-called salvage therapy approaches. One of the challenges with this, and it speaks to the issue that Mitchell mentioned about the number of patients who were collected but didn’t actually get the product, is not so much creating the product fail, but bridging these patients who often have very rapidly progressing disease, finding the therapies that can keep their disease under sufficient control and without too high a burden to allow them to get to that CAR administration is still something I think the field needs to work out in more detail.

Smith: I agree with that, and then on the other hand, there are people who respond and then relapse. There were abstracts here talking about mechanisms of resistance. In the ALL [acute lymphocytic leukemia] story, the cells learn to splice out the target, which is quite fascinating. There seems to be a little bit of that in DLBCL [diffuse large B-cell lymphoma], but maybe not quite as much, but are those T cells, are they exhausted? Can we re-stimulate them with immune-modulating agents by specific antibodies? I think there will be a number of areas that we can advance. What are some mechanisms of resistance? Can we overcome that and make these more feasible? Ultimately, if it can be an outpatient procedure and we can follow and re-stimulate those cells or keep them from getting exhausted, I think there is room. This is the early stages, so I think there is room to make this technology more effective.

Sweetenham: A lot more promise for the future. Thanks to Mike Williams and to Mitchell Smith for spending some time with us and sharing your insights. Thank you.


last updated