Navigating CAR T Decision-Making in R/R DLBCL

The expanding use of chimeric antigen receptor T-cell (CAR T) therapy is reshaping treatment decisions in relapsed/refractory diffuse large B-cell lymphoma (DLBCL); however, patient selection, referral pathways, and treatment logistics continue to influence real-world use. During a live Case-Based Roundtable event with oncologists in Bernardsville, New Jersey, Lori Leslie, MD, director of the Indolent Lymphoma and Chronic Lymphocytic Leukemia Research Programs at Hackensack Meridian Health John Theurer Cancer Center and assistant professor at Hackensack Meridian School of Medicine, led a discussion about selecting appropriate candidates for CAR T-cell therapy, explaining the treatment process to patients, and real-world barriers to access.

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Targeted Oncology^TM: How do you determine the appropriate treatment option in the second line?

Lori Leslie, MD: The first CAR T for relapsed/refractory DLBCL was approved by the FDA almost a decade ago; it was in 2017,¹ so it's really been a while [since FDA approval of CAR T] in the third line. More recently, [CAR T] was approved in the second line, where it still has already been several years.^2,3

Dr Jason Westin, Dr Laurie Sehn, and colleagues came up with an algorithm for second-line treatment decision-making once we had CAR T approved in second line and there was more than 1 product available. This is an algorithm that was published in 2022 and is already slightly out of date when you look at the second- or third-line therapy options because it does not include bispecific antibodies. But when you look at patients with relapsed disease, most of those relapses happen within the first year after finishing their treatment. So that's the highest risk period—about 75% of patients.⁴

The decision point is: Are they eligible for CAR T from a comorbidity perspective or a logistical perspective? Just medically speaking, about 70% would be eligible to go onto CAR T, where it's recommended to get axicabtagene ciloleucel [Yescarta; axi-cel] or lisocabtagene maraleucel [Breyanzi; liso-cel]… and then about 30% to 40% of those patients,⁴ I would say conservatively, do not relapse, so the projected cure rate is about 20% of all second-line DLBCL.⁴ [The proportion of those] not eligible for CAR T [are listed in the algorithm at] about 30%,⁴ but I think as we've learned more about CAR T, that number is probably a lot smaller from a medical perspective. Initially, when CAR T was first approved, we used to think of eligibility similar to what we thought with an autologous [stem cell] transplant; you need to be younger, you need to have good organ function. Now, we realize CAR T for patients in their 80s is pretty common. I think our oldest patient at Hackensack was about 89. Some centers have treated patients who are fit 90 –year olds; we've treated patients on dialysis with pacemakers. So, I think our understanding of how to manage the anticipated toxicities of CAR T has changed enough that that 30% is probably slightly lower in current practices. But then you go on to other second-line therapies or third-line options that one would consider as well as now bispecific-based therapy. Those patients relapsing beyond a year, you think about if they're eligible for CAR T. So technically, axi-cel is for patients who have relapsed within a year. Liso-cel does have eligibility for patients who are not transplant candidates, so if they're not a transplant candidate, then they can still get CAR T in the second line even if they are beyond a year for all of the products. Otherwise, there are a proportion of patients that still do get high-dose [chemo]therapy and autologous transplant, particularly those patients who have relapsed later.

How do you explain the mechanism of CAR T and the treatment process to patients?

This looks a little bit different if we are at a CAR T center or if we are partnering with a CAR T center to have the patient get their therapy there and then come back. I like to explain to the patients that we're reengineering their own immune system to do what it should be doing, which is recognize and eradicate cancer cells, so you're trying to restore that immune surveillance.

How that works? The patients are referred, they need to have insurance approval, then they go through leukapheresis, which I usually explain to patients as... a dialysis machine where they take out the T cells and put everything back. Then they're shipped off to be manufactured, during which time the patient might get bridging. That can be at the treatment center or at a local center; it depends. Even before leukapheresis, during the waiting period where you're getting insurance approval and getting the patient in, there's a leukapheresis bridging, which we think about differently than post leukapheresis in terms of our options. And then the patients typically get lymphodepleting chemotherapy, a few days of rest, and then their infusion. At Hackensack, we're still mostly doing the infusions inpatient. There are some situations in which we do outpatient CAR T.

Then, at various time points, once they're deemed to be through their CAR T process, the patient typically goes back to the community oncology care for continued follow-up. Historically, at our center, that was usually around 3 months post CAR T. I think in New Jersey, we're a very dense area, so usually the referring centers aren't too far away. That 3 months has been getting shorter the more comfortable everyone gets with CAR T, and I know some centers are now sending patients back after a few weeks just to continue that care closer to home.

Of patients with relapsed LBCL who meet the medical eligibility criteria for CAR T, what proportion ultimately receive it in the real-world population?

It's on the lower end of the spectrum on real-world studies… In general, in the United States, it is quoted to be somewhere around 20% conservatively,⁵ sometimes as high as 30% to 40% in more modern [estimates]… [In] Europe, somewhere between 29% to 71% of patients estimated to be eligible do not receive treatment as of 2020.⁶ I think that this number is getting a little more optimistic as time goes on. We get more comfortable with CAR T, we get more comfortable identifying patients who might be candidates, and the eligibility for CAR T gets broader. But it remains to be a major barrier—getting CAR T to patients that are actually eligible and could potentially benefit.

What are some of the factors or barriers that lead to the patient not being able to receive CAR T?

They’re multifactorial; some are patient-related barriers, some are physician or provider-related barriers. Logistically, it's challenging; [it’s] a little easier [here] in dense New Jersey to go to a treatment center probably within an hour or two. In the center of the country, some people have to travel over 4 hours to get there. Sometimes the patients are quite sick from their disease, so even traveling short distances might be hard, and they need to start something relatively urgently.

And there's maybe some misconception about how quickly patients can actually get in and get approved and get to their CAR T. Patients are nervous; [the CAR T mechanism] sounds like science fiction. They're used to chemotherapy and cycles, and you tell them you're going to reengineer their immune system. Some patients initially have a shock from that and are worried that they have to be in the hospital for 10 days, and that can be a significant barrier for some people.

[CAR T can be] costly—not only the treatment, which hopefully is covered, but then if they need to stay locally at a hotel or just travel back and forth, or if they can't drive after CAR T, getting around to appointments postinfusion is something that's a significant barrier for a lot of patients.

And knowledge gaps in efficacy and safety of CAR T are still out there… There’s some concern about adverse event [AE] management. Patients can still need AE management once they go back to the referring provider, and maybe there's not infrastructure in the clinic to take care of intravenous immunoglobulin and transfusions; a patient might need a bone marrow biopsy, things like that.

Logistically, sometimes there are some barriers getting into the CAR T such as communicating with the office. Maybe there's not a specific provider to reach out to get the patient in quickly. And then finally, the caregiver support: the patient does need to have a caregiver that can help them once they go home and help them get to appointments, so sometimes that can be a barrier as well.

DISCLOSURES: Leslie previously reported consulting/advisory roles with, travel support from, speakers bureau roles with or other relationships with AbbVie, ADC Therapeutics, AstraZeneca, BeiGene, Bristol Myers Squibb, Celgene, Eli Lilly, Epizyme, Evolveimmune, Genmab, Janssen, Karyopharm Therapeutics, Kite/Gilead, Merck, Pharmacyclics, Roche/Genentech, Seagen, and TG Therapeutics.

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REFERENCES

1. Kite’s Yescarta™ (Axicabtagene Ciloleucel) Becomes First CAR T Therapy Approved by the FDA for the Treatment of Adult Patients With Relapsed or Refractory Large B-Cell Lymphoma After Two or More Lines of Systemic Therapy. News release. Kite Pharma. October 18, 2017. Accessed July 23, 2026. https://tinyurl.com/4nyvc42d

2. Sharma P, Kasamon YL, Lin X, Xu Z, Theoret MR, Purohit-Sheth T. FDA Approval Summary: Axicabtagene Ciloleucel for Second-Line Treatment of Large B-Cell Lymphoma. Clin Cancer Res. 2023;29(21):4331-4337. doi:10.1158/1078-0432.CCR-23-0568

3. Elmacken M, Peredo-Pinto H, Wang C, et al. FDA Approval Summary: Lisocabtagene Maraleucel for Second-Line Treatment of Large B-Cell Lymphoma. Clin Cancer Res. 2024;30(11):2309-2316. doi:10.1158/1078-0432.CCR-23-2967

4. Westin J, Sehn LH. CAR T cells as a second-line therapy for large B-cell lymphoma: a paradigm shift? Blood. 2022;139(18):2737-2746. doi:10.1182/blood.2022015789

5. Newell A, Fortune EE, Gonzalo M, Saxton MC. The burdens associated with receiving CAR T-cell therapy: A qualitative study of CAR T patients and caregivers. Presented at: Tandem Meetings of ASTCT and CIBMTR; February 4–7, 2026; Poster 430.

6. Canales Albendea MÁ, Canonico PL, Cartron G, et al. Comparative analysis of CAR T-cell therapy access for DLBCL patients: associated challenges and solutions in the four largest EU countries. Front Med (Lausanne). 2023;10:1128295. Published 2023 May 30. doi:10.3389/fmed.2023.1128295