Bridging Therapy in R/R DLBCL


Ian W. Flinn, MD, PhD: I want to dive deeper into the discussion about bridging therapy. We hear that the people who are the worst off probably get bridging therapy because you can’t hold them. Is there 1 therapy that you use over another because you think, 1, they’re going to respond to it; or 2, it’s not going to cause problems for you down the line in terms of adverse events; it’s going to be better? Or is every patient just different?

Kami J. Maddocks, MD: There are a few ways to look at it. First, do they need bridging therapy if they have symptomatic disease? If they have rapidly progressing disease, they’re probably going to need it. If it’s something you can hold off on, it’s better not to do it.

Looking at when to give it, how do you define bridging therapy? Do you define it as before cell collection, like getting them to the actual CAR [chimeric antigen receptor] T consult, or the apheresis of the cells? Or do you define it from when they collect the cells to being able to give it? 

If you’re thinking about giving them something to be able to get to the collection, you probably want to avoid things like bendamustine or BR [bendamustine, rituximab]–polatuzumab, so maybe use polatuzumab alone. Whereas if giving something after they’ve already collected those cells, maybe a cycle of something like that is OK.

There is a role for radiation here. If you have 1 area that’s more problematic or symptomatic than others, it seems that in non–GC [germinal center] patients, I’ll think about using ibrutinib or something like that as a bridging therapy if possible. This depends on whether it’s before or after collection.

Ian W. Flinn, MD, PhD: You brought up ibrutinib. Loretta, there were data this year at ASH [American Society of Hematology Annual Meeting] suggesting that ibrutinib might be helpful in certain situations, and we’ve seen the data previously reviewed in other disease states, like CLL [chronic lymphocytic leukemia]. It’s not that easy to get for patients with large B-cell lymphoma, but are you using ibrutinib routinely or in select patients?

Loretta J. Nastoupil, MD: Not routinely. I agree with Kami’s comments. All of us are trying to figure out ways to optimize using the therapy. We know that T-cell fitness may lead to better efficacy. We also saw glimpses of that with the ZUMA-12 trial, where you see more robust expansion if utilizing the drug in patients who’d had only 2 cycles of chemotherapy. As you mentioned, that area under the curve didn’t translate into worse safety profiles. So any strategy that might impact T-cell fitness is worth exploring. Where we struggle with interpreting the data that currently exist is none of it is randomized. We don’t know how much of an impact there is. I agree that I’ve been underwhelmed when trying to get it and stabilize a patient with large B-cell lymphoma. But it’s still worth exploring.

Transcript Edited for Clarity

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