Optimal Approaches to Bridging Therapy in DLBCL

Greg Nowakowski, MD, explains optimal approaches to bridging therapy before CAR T cell therapy in DLBCL.

John Leonard, MD: Greg, what’s been your approach at Mayo Clinic for bridging therapy? That comes up, and I can recall patients where they had a substantial amount of disease. We were working on the CAR [chimeric antigen receptor] T cells. They had responded to some chemotherapy to get their disease down a little. But we knew we were going to go to CAR T, and the question was well, should I give them another cycle of chemotherapy? But then if that cycle doesn’t work and they blow through it, then the CAR T chance of working is going to be lower. It’s like many other things, but it seems to be magnified here because in autologous transplant, we would just say, well we’re not going to do it. It’s not going work in this patient. But in CAR T it could work, even though the disease was chemotherapy-refractory. This seems to come up a lot. How do you tend to think about it, and what agents do you tend to use when you do some sort of bridging?

Greg Nowakowski, MD: There’s no one-size-fits all here. It tends to be very personalized, and it depends a little on if the bridging starts before collection apheresis or after, when we don’t have to worry so much about the suppressing of T cells. The other factor is, is the bridging done because patient has progressive disease causing compressive symptoms, or more of a deterioration in performance status or organ function? Because this will obviously result in a choice of different bridging. In general, I tend to avoid other anti-CD19 therapies in this space until we get more data that indeed those therapies do not interfere later on with CAR T-cell efficacy or CD19 expression. We are getting there. I think we’ll know over time more, and maybe it will work just as well to bridge with some of those other CD19-directed therapies. But as of now, I tend to avoid those. For patients who are not collected yet, I like using polatuzumab in combination with Rituxan, and sometimes avoiding bendamustine, to try to not to decrease the amount of T cells for the collection. If they’re already collected, then I have no hesitancy in using Pola+BR [polatuzumab, bendamustine, rituximab] in this setting, and I use it quite frequently. A gemcitabine-based chemotherapy for a patient, particularly one who was exposed previously to bendamustine or polatuzumab, would be another option. So GEMOX [gemcitabine, oxaliplatin], or gemcitabine as a single agent, or gemcitabine with rituximab would be a reasonable option there.

There’s a subset of patients who have 1 or 2 dominant masses, and they’re rapidly progressive and have compressive symptoms. Those patients can benefit from radiation, and you’re avoiding some of the systemic toxicity. In my experience, radiation has been quite effective, even in patients with very chemotherapy-refractory disease, to at least shrink the dominant mass, or the mass that is causing the most symptoms, and allow a patient to bridge to a CAR T-cell therapy. Finally, all good steroids, these friends of ours in practice for a very long time, high-dose steroids with Rituxan. They do work, and we always worry about the suppression of T cells as well, so we tend to use it in patients after the collection is done. But they do work, and particularly in patients who develop systemic symptoms…duration and performance status. Sometimes high-dose Solu-Medrol with rituximab can result in performance status that is controlled prior to moving to CAR T cells.

John Leonard, MD: Cyrus, I think this is an important point, I want to get your take also. The issue of, you’re getting ready to refer a patient to CAR T, their T cell haven’t been collected yet, and yet you need to do something quickly. Greg mentioned the steroids, he alluded to bendamustine. I want to get your take, do you pretty much tell people to agree with that? I have to say, about a week ago, I had a patient I was referring. I called our cell therapy team, I wanted to refer somebody who hadn’t been collected yet, and the patient was symptomatic. I’m sitting there brainstorming by text with my colleague about what to give, and I’m like, “Well I guess I could give some steroids.” And, “No, no, no steroids.” Is it a good rule of thumb to avoid, or any other tricks as far as that goes? I don’t know if that’s data driven, it makes a lot of sense. I don’t know if there are data showing that impedes things. But it certainly makes sense between that and the T-cell effects of bendamustine.

Cyrus Khan, MD: I think if you allow enough time between whatever you’re using as precollection treatment and the collection, it will be OK. I think we’ve got to do what we’ve got to do for those patients, naturally, to be able to reach that and collect them. Two of my favorite approaches are single-agent polatuzumab and gemcitabine, oxaliplatin. Gemcitabine, oxaliplatin is a tried and tested regimen. You can admit the patient and give it very quickly without getting authorization and waiting for it, if you need to give it quick. Polatuzumab of course is quite a nice, clean drug to get them to that point. Then I also give another dose as a bridge to CAR T. Those have been at least my 2 favorite approaches for getting those patients to that phase.


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