Improving Outcomes in Relapsed/Refractory Diffuse Large B-Cell Lymphoma - Episode 4

Role of CAR T-cell Therapy in R/R DLBCL

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John P. Leonard, MD: We would all argue that a patient who is a transplant candidate is going to get a second line chemotherapy regimen, whether it’s RICE [rituximab, ifosfamide, carboplatin, etoposide], RGDP [rituximab, gemcitabine, dexamethasone, cisplatin] or 1 of the other platinum-containing regimens. Certainly if I have a CR [complete response], they’re going to go on to get an autotransplant as of today. There were some data presented at ASCO [American Society of Clinical Oncology Annual Meeting] suggesting that even if they had just a PR [partial response], they could do well with an autotransplant. That’s an area where there has been some uncertainty, and we’ll come back to that in a few minutes.

Patients who get autotransplant and relapse or are multiple refractory CAR [chimeric antigen receptor] T cell have become the standard approach, assuming the patient is a candidate. I’m going to ask you, Matt, to give us a brief summary of the 3 leading agents in the setting and how you think about them. We will come back to some of the new data presented at ASCO and otherwise. How do you think about CAR T cell, Matt?

Matthew Lunning, DO: When I see that primary progressive or primary refractory patient in the frontline setting who is transplant eligible, I’m already starting to discuss CAR T-cell therapy at their initial visit. While they can go on second-line platinum-containing regimens, I still think there is a high probability that they’re not going to have chemotherapy-sensitive disease and that I’m going to want to take them down the path of a consolidated transplant.

CAR T cell is such a complex process. Just wait until 2 to 3 cycles of second-line therapy, then drop that discussion and it can leave their heads spinning. There are a lot of logistics to do a CAR T cell, like there are a lot to get into doing a transplant. Having already started that process or having people aware that you could go down this road, when that PET [positron emission tomography] scan occurs that doesn’t show that a response is amenable to consolidated transplant, you can quickly pivot to CAR T cell. That’s the important part that we’re all preparing for, both in the commercial setting and previously in the clinical trials. Right now, there are 2 commercially available CD19-directed CAR T cells: axi-cel [axicabtagene ciloleucel] and tisagenlecleucel. They both had single-arm data, both with the ZUMA-1 as well as JULIET. Liso-cel [lisocabtagene maraleucel] is in late-stage development and has been presented multiple times, yet it is to be published from the TRANSCEND [NHL 001] data. I described them as all 3 apples. They’re not apples and oranges, but they’re 3 different types of apples. They could be Fuji apples, Red Delicious, and Granny Smith apples. They do have subtleties to them, just as each apple may taste a little different, but they’re still apples. The overall response rates are, on average, 70% to 80%, their CR rates are anywhere from 40% to 50%, and their PFS [progression-free survival] actually lines up at around 6 months.

There are still a lot of patients post CAR T cell who are progressing. But on the flip side, there appears to be durability. If you can get to CR in 6 months, 30% to 40% of the patients may derive benefit to the point where you’re just starting to discuss that this is now 3 chances to cure diffuse large B-cell lymphoma up front after an autotransplant and potentially after CAR T. For those double-refractory patient populations, if you have your ducks in a row, you could get that narrow window of disease stability and go to a CAR T cell. You have to be previously treated with 2 lines of therapy to get a commercially available CAR T. I still think there is room for improvement in clinical trials in CAR T from that standpoint.

John P. Leonard, MD: From the available or close-to-available agents, what’s your quick-and-dirty bottom line? I know there are a lot of researchers, a lot of studies trying to compare apples and oranges. To me, it seems like they’re more similar than they are different, but what are the key distinctions from a clinical perspective?

Matthew Lunning, DO: I try to get the CAR T cell that I know, when I perform apheresis, will be coming back and I can infuse it. We’ve gotten better over the last 5 to 6 years that we’ve been trying to manage toxicities. We’ve gotten better at managing toxicities, and we’re looking at strategies to manage toxicities better to try to prevent those grade 3, 4 CRS [cytokine release syndrome] and neurological events but being mindful that you don’t want to affect the efficacy of the therapy by the risk-mitigation strategies you’re using.

Getting it out and getting it back in the shortest period of time is key because large-cell lymphoma doesn’t care that the coronavirus [pandemic] is going on or that it’s the weekend or a holiday; it’s going to grow. What the data are showing us is that ALK matters. LDH matters. You don’t want to perform apheresis and not infuse.

Transcript Edited for Clarity