The Evolving Treatment Landscape in Relapsed/Refractory Diffuse Large B-Cell Lymphoma - Episode 10

Treating R/R DLBCL With CAR-T: Current Barriers

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Ian W. Flinn, MD, PhD: Loretta, you’ve published in the area of real-world data, and there are multiple publications looking at these different products. One of the arguments that came out when ZUMA-1 was published with axi-cel [axicabtagene ciloleucel] was, “You can never re-create those patient populations.” There was such a bias stating that the results of people who went on the trial wouldn’t reflect what’s going to happen when this becomes commercially available. Were those skeptics? Is this validated with the real-world data, or is it better than that?

Loretta J. Nastoupil, MD: I always pause and recognize that it’s not the real world, right? If we were looking at the real world, we’d look at every large B-cell lymphoma patient out there, not just the ones who are treated at The University of Texas MD Anderson Cancer Center and other centers where we collaborated with folks who had experience on ZUMA-1. If you take patients who would not have qualified for ZUMA-1 for various reasons and look to see what their outcomes are, across the board we have shown that you can reproduce the findings of ZUMA-1 and JULIET. We’re all eager to see if we can reproduce the findings of TRANSCEND-NHL-001 once we collect real-world experience at the centers that have experience.

There were a number of patients who got standard-of-care products who never would have qualified for those prospective studies because they were too frail, too sick. That is reassuring to me. Despite the population being skewed in that direction, we don’t see differences in safety particularly. We can reproduce the efficacy. I do think that provides much more ammunition to that argument that this is just a boutique therapy that’s only going to be offered in select centers. I think it should be offered to every relapsed/refractory large B-cell lymphoma patient. Where we’ve struggled is to get more access to patients. We’re just looking at the folks who get through our door. There’s a huge portion who never get there, and part of it is logistics and the perception around the toxicity.

You asked this question to Kami. In my experience, there is clearly a difference in the toxicity profile, at least in the first 30 days. There might be financial reasons why a center may choose 1 construct over the other. How much of that translates into efficacy? Probably very little. It’s more in terms of when you expect that fever to occur, can you give it outpatient vs inpatient? But we have shown that there will be differences in the patient population, depending on the construct, because of that safety perception. But the efficacy looks to be just like what we saw in these prospective studies.

Ian W. Flinn, MD, PhD: You brought up some of the barriers regarding why not as many patients get treated with this as should. Some of that has to do with access, financial barriers, social barriers, and such. There are also issues with delivering the therapy once you’ve acquired the cells, Loretta. Some products take longer to give than others. How does that factor into your decisions about which product to give? Some data suggest that bridging therapy is not your friend, right? It doesn’t necessarily improve outcomes. It may be necessary, but it doesn’t necessarily improve outcomes. How does that factor into things?

Loretta J. Nastoupil, MD: As we get more experience, we’ll get much better at this. It still boils down to patient selection. And not surprising to me, anytime you have to utilize bridging therapy it’s because the patient has a much worse prognosis, much worse disease status. And so you don’t have the luxury of waiting during that 3- to 4-week window while you’re undergoing manufacturing. The other aspect is we have to be stewards of our practices. This is super expensive and requires a huge demand of health care resource utilization. There will be differences in terms of which construct you might select based on where you practice as well.

That forces us to revisit how we do this, in terms of not only inpatient vs outpatient but also our networks. Can you broaden this out? We saw data at ASH [American Society of Hematology Annual Meeting] looking at centers that are not traditional university settings but for big groups like Sarah Cannon, like US Oncology. It can safely be done in those settings as well. That just provides reassurance to me that as we get more experience, we’re probably getting better at the delivery of this therapy.

At the end of the day, what matters most to patients is, are you going to have successful manufacturing, and are you going to be able to live long enough to get this therapy? That falls on us, as physicians, to do a better job of selecting patients. As more treatment options become available, not every patient is a CAR [chimeric antigen receptor] T patient. Some of these other therapies, if they’re just as effective, might take up some of that space.

Transcript Edited for Clarity