Factors That Inform Sequencing of Therapy in Relapsed/Refractory DLBCL

Transcript:

Matthew A. Lunning, DO, FACP: It's a funny analogy, I think you look back 10 years ago in relapse refractory large–cell lymphoma, and we were playing checkers and now we're playing chess. We have several pieces on the chess board here and it's trying to sort out what chess piece to move and what one to bring out early. Do you bring your queen out? Bishop and knight, with all of these therapies? I'll put it to the faculty here. Sequencing is a real deal, and as we have Tafa-Len [tafasitamab plus lenalidomide] available in the second line, we now have T-cell engagers or bispecifics, in third line and beyond. We have CAR T cell second line with the survival advantage. We have the pilot data expanding the fringes, if you will, of those transplant or CAR T cell eligible transplant ineligible patients. Where are we Dr Flinn, how are you playing chess against the large–cell lymphoma these days?

Ian W. Flinn, MD, PhD: A lot of it begins with the question, as we've been discussing, is the patient a CAR T cell candidate? But also, is that today or is that tomorrow? So, if you're choosing a therapy, we heard earlier that in the dislike for bendamustine because of its effect on T cells. So, if you thought that maybe you couldn't get the patient to CAR T cells now, but you might be able to do it later, then you certainly want to keep that in your back pocket and not use bendamustine, maybe use the … regimen to do that. If the person's never going to be a candidate, then I think some of these other therapies come into play a little bit more easily, like the other 19-directed therapy: the Tafa-Len, the loncastuximab, and so forth. Even if you are using those therapies, I think there's data that's at this point, largely anecdotal, but there's data that suggested that you're not taking CAR T off the table. And so, you should be able to use those therapies if you must use it; you shouldn't be shy about doing that.

Matthew A. Lunning, DO, FACP: Dr Wang, how are you thinking about second line large cell and kind of pieces on the chess board? Do you have one move that you're always going towards?

Yucai Wang, MD, PhD: I usually give the best therapy, or namely I find a curative intent therapy first.

Matthew A. Lunning, DO, FACP: So, you're asking yourself, is it curative intent or not curative intent type of a patient situation?

Yucai Wang, MD, PhD: Correct. For example, the primary refractory disease, early relapse, like in the trials, then we prioritize CAR Ts for those if feasible. If it's a late relapse, you can still consider transplant be on the table, but if you're not transplant eligible, then you go to CAR T. You always find the curative intent therapy for the patient.

Matthew A. Lunning, DO, FACP: Dr Westin, just coming back to your point, performance status is often a subjective thing, but it's also a lymphoma specific thing versus a disease or a nonlymphoma-related event. The data that you're commenting on and trying to move the pieces around, can you make a CAR T cell ineligible patient based upon lymphoma have a response and then they become CAR T cell eligible in later lines?

Jason Westin, MD, MS, FACP: Absolutely. Dr Flinn was commenting on if this person could become CAR T cell eligible, then you would want to be cautious about what therapies you're giving, not to do too much damage to their immune system, such that you might burn a bridge. The quality of the T cells that are apheresed matters when you're making a CAR T cell, and we've seen that with moving from third line to earlier lines for CAR T cells. These are different T cells. Giving lots and lots of chemotherapy has an impact on patients across the board, but specifically on their T cells. I think using bendamustine in a patient that is potentially going to get CAR T cells, you could make that patient more fit, but you might mean that their CAR T cell is going to have less of a benefit. In that patient, I would consider improving their fitness, but using something else. Tafa-Len would be a good option to consider, loncastuximab, or the pola-R regimen. Bispecifics, as he mentioned, are coming into that space as well. You can certainly work to try and improve a patient's fitness so that maybe they would benefit from a CAR.

Transcript edited for clarity.