R/R DLBCL: Transplants in the Era of CAR-T

Ian W. Flinn, MD, PhD: As I was listening to you, I was almost depressed. The 2 of you remarked on all the obstacles associated with putting a patient on CAR T-cell therapy. But we have to remember that prior to the introduction of CAR [chimeric antigen receptor] T-cell therapy, all these patients would die. Now we have a therapy that has long-lasting duration of remission and cure, and 40% of patients are eligible for these trials.

Loretta, that makes you wonder, right? If it’s so great a therapy in patients who have relapsed after an autologous transplant or are refractory-ineligible—they never make it to a transplant—why are we transplanting people? Maybe we should just be going directly to CAR T-cell therapy.

Loretta J. Nastoupil, MD: We have 3 randomized studies that are asking that same question. There’s strong enough rationale, at least in the third-line setting, to go head-to-head with transplant. It is defining the population that’s most likely to fail transplant, and those patients progressed within 12 months of frontline rituximab and CHOP [cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone]–like treatment, so I have a lot of optimism that those studies will be positive. If they are, then transplant will probably disappear.

I was also disheartened by all the frustrations that were voiced, but I agree that all statements are absolutely correct. The systems are not designed well for CAR T, but that provides 2 opportunities. One is to revisit how we do things. We’re not going to be able to address the insurance approval. You have to have a champion on both sides, and I oftentimes service that champion on this side. I am more than happy to push a patient through the system if I know about them. This has forced us to create these relationships where we share cell phone numbers and emails with folks on the front line, because it’s much more likely to go quicker if you know someone on the inside who can push that patient through. Otherwise, there’s no reason to even continue to pursue CAR T, hearing what we just heard. We should be focusing all our effort on trying to find more effective, more readily available therapy. 

John M. Burke, MD: That’s a great point, and I would emphasize the importance of both, right? We have this technique, CAR T, that’s going to save lives. We have to do everything we can to maximize the utilization of the technique, as we’ve outlined.

But at the same time, those barriers are still there and it’s hard to imagine snapping your fingers and having somebody go from my clinic to a tertiary center the next day. And so at the same time we need to broaden the scope of the availability of CAR T-cell therapy. We need to deliver it more safely. We need to expand where it can be delivered. And we need to find other therapies that can achieve the same degree of success, that don’t require so much effort to make to happen. 

Ian W. Flinn, MD, PhD: Maybe we should also be refining our understanding of who’s most likely to benefit and who’s likely to get the adverse events associated with that treatment.

Kami, do we know anything about who’s likely to get cytokine-release syndrome [CRS]? Who’s likely to get neurotoxicity? Does tumor bulk matter? Do prior therapies matter? How can we improve outcomes, or at least our patient selection?

Kami J. Maddocks, MD: We know that patients with rapidly progressing disease, high LDH [lactate dehydrogenase] levels and high CRP [C-reactive protein] are more likely to have increased toxicity. Looking at the role of early referral, as everybody has mentioned, is key. Identifying patients who will benefit is key. When I look at a patient who is not a candidate for transplant, but I still think they’re a candidate for CAR T, I’m going to refer them early for CAR T. Even though I don’t think they’re a candidate for transplant, I say, “Oh, I’m giving them something.” And then I look at the role of bridging therapy, which is something that I don’t think everybody should receive. We need to decide who is going to benefit from bridging therapy and what that bridging therapy is.

Ian W. Flinn, MD, PhD: Do you have to have active disease, Kami, to get CAR T-cell therapy? I’ve been in the fortunate situation a few times where you didn’t think a patient is going to respond to anything. But I collected the CAR T cells, gave them bridging therapy, and all the disease went away. Should I hold that therapy? There’s a notion that you need a target to go after. There are some data on this from some of the trials. It’s not a common situation, but what are your thoughts?

Kami J. Maddocks, MD: We have had some patients who have at least by PET [positron emission tomography] scan gone into a surprised CR [complete response] and went ahead with CAR T-cell therapy. Whether they’re still in remission because they were going to be in remission with or without that, I guess I can’t really speak to.

Transcript Edited for Clarity