Applying New Data to Treatment Selection in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma - Episode 12
The panelists share their approach to the treatment and work-up of patients who require salvage therapy.
Grzegorz S. Nowakowski, MD: Unfortunately, a significant proportion of patients will relapse after CAR [chimeric antigen receptor] T-cell therapy. We already discussed that this is a very difficult population to treat. How do you approach those patients at the time of relapse? Do you rebiopsy to assess CD19 expression? Are there other CD19-targeting therapies available? How do you work up those patients prior to initiation of salvage therapy?
Caron Jacobson, MD: The answer is to biopsy anybody who has a safe tumor to biopsy. We should biopsy everybody to check CD19 to think about sequencing other therapies, and we also routinely check PD-L1 expression in the tumor and tumor microenvironment because the patients who have overexpression of PD-L1 may respond very nicely to checkpoint inhibitors in this setting, and you could bridge them to an allogeneic transplant. There’s also a ton you can learn, maybe to look for things that we don’t even know to look for at this point. We all have biobanking studies where we can bank extra samples so we can ask those questions in the future. This is a black box for us, as we already mentioned. The unmet need is how to rescue someone who fails CAR T-cell therapy, and these biopsies are going to be an important answer.
Matthew Lunning, DO, FACP: Sometimes you get a surprise retrograde biotransformation or retrograde relapse where the CAR T cell took care of the aggressive component and you get a follicular lymphoma on the biopsy, which may change your treatment paradigms or you may do something differently.
Caron Jacobson, MD: I don’t believe that. CAR T gets rid of it all.
Matthew Lunning, DO, FACP: I don’t think so, but I’ve been surprised where you’ve seen this occur, maybe not in the CAR T-cell world.
Grzegorz S. Nowakowski, MD: The lesson remains the same in lymphoma: always biopsy.
Frederick Locke, MD: Always biopsy. And after CAR T-cell therapy, responses are very dynamic within the first 3 months. With that 1-month scan, you’re going to pick up if a patient progresses through CAR T-cell therapy. Unfortunately, around 20% might have their tumors grow. But it’s the 3-month time point that matters. In fact, data looking at circulating tumor DNA suggest that even patients with some PET [positron emission tomography]–positive disease may not have any tumor there. They may have negative circulating tumor DNA, which predicts for long-term remissions. We have to take what we see on that 1-month PET with a grain of salt. I agree with Caron, we should biopsy all these patients who are progressing after CAR T if it’s safe.
Matthew Lunning, DO, FACP: I find the day 29, 1-month PET to be incredibly confusing. It’s very helpful if it’s in metabolic CR [complete response], but other than that, it’s very confusing.
Frederick Locke, MD: It’s helpful if it’s frank progression. If it’s metabolic CR, you can tell the patient, “This is great.” But we still get it because I want to know if the patient is clearly progressing, I want to have that conversation and start to plan the next thing.
Leo Gordon, MD: We still do it. I’m still following the algorithm of the clinical trials. I haven’t changed that. But I’m comfortable with the day 30 PET.
Matthew Lunning, DO, FACP: We have some trouble getting it paid for. It seems like I’m on a continual peer-to-peer to get it paid.
Leo Gordon, MD: Yes. It depends on how many you’ve done before.
Frederick Locke, MD: Yes. This is a regional thing too. You brought this up, Matt. In Florida, we have 5 major payers, so we’ve worked out those 5 major payer relationships. But when we get a small payer or someone from out of state, it’s a slog. It’s regional.
Matthew Lunning, DO, FACP: They make you choose. “Day 29 or day 100? Which do you want?”
Frederick Locke, MD: Yes.
Leo Gordon, MD: Yes, we’ve had that.
Grzegorz S. Nowakowski, MD: What’s your experience using CD19-targeting therapy post CAR T-cell relapse? Either loncastuximab or tafasitamab with lenalidomide.
Leo Gordon, MD: We’ve used the loncastuximab some, but I haven’t seen a lot with that. Anecdotally, in the few people whom we’ve done it in, we haven’t seen much.
Matthew Lunning, DO, FACP: In the LOTUS trial, they published a subset of the patients who got loncastuximab tesirine after CAR T cell, and there were some responses showing durability in a small patient population. To Caron’s point, what’s the carrot? If you get a CR after CAR T and you give loncastuximab, are you dangling the allogeneic [transplant] carrot in front of them or an autologous [transplant] carrot? It’s a destination in some younger population therapy.
Leo Gordon, MD: We’ve tried. There’s a trial that Matthew Frank is doing at Stanford [University] with a CD22 CAR, and what he’s presented looks encouraging. We’ve sent a couple of patients his way. Looking at another target is worth doing.
Transcript edited for clarity.