Elimination of REMS Program Could Reduce Barriers to CAR T in DLBCL

Chimeric antigen receptor (CAR) T-cell therapy is increasingly preferred as therapy for patients with early relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL). Physicians may opt against CAR T-cell therapy for reasons including barriers to patient access, some of which were recently reduced by the FDA’s update to the labels of approved CAR T-cell therapy. In a Community Case Forum event in Pittsburgh, Pennsylvania, Nathan Denlinger, DO, MS, assistant professor in the division of hematology at The Ohio State University College of Medicine in Columbus, Ohio, discussed this change and other considerations such as bridging therapy when using CAR T-cell therapy.

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Targeted Oncology: What do the NCCN guidelines recommend for bridging therapy for DLBCL?

Nathan Denlinger, DO, MS: In theguidelines with relapse [within] 1 year, we have category 1 evidence; it is pretty straightforward that you're going to use CAR T-cell therapy, whether it's axicabtagene ciloleucel [axi-cel; Yescarta] or lisocabtagene maraleucel [liso-cel; Breyanzi], and there are a variety of different bridging regimens that they put in [the guidelines].¹ One thing to be careful about is that bendamustine has to be after CAR T collection. Often, we don't employ it, because if they fail manufacturing, and you have to recollect, that does worry us. People have used it, and it works pretty well; you can get rid of a lot of disease that way. But bendamustine prior to CAR T cell therapy collection is bad.

Radiotherapy is a great bridging therapy. [Also included are] the standard chemotherapy combinations. We often use rituximab [Rituxan] plus polatuzumab [Polivy] by itself, without the bendamustine, and that seems to work well. It doesn't cause any delays in CAR T. We usually have the local [oncologist] do rituximab plus polatuzumab or some of the bridging therapy, whatever the local physician and the patient want.

What considerations can affect whether a patient is able to get CAR T-cell therapy?

CAR T is category 1, but we still have to think about different things [to determine if] they are candidates.² That’s going to be performance status, comorbidities, and organ function. We’re also going to be thinking about things like financial situation and caregivers. Most patients can get it unless they're doing [extremely] poorly.

High disease burden can need immediate treatment. Patient hesitancy, financial burden, and lack of insurance coverage can be an issue. We've had good luck getting patients’ insurance to [cover] CAR T…. The financial burden is the same as the financial burden of almost any other treatment. They're going to meet their out-of-pocket maximum, but there's nothing above that. There's a financial burden on the system for the cost of the product, but if you compare that with bispecific T-cell engager therapy, it's equivalent, if not cheaper, because it's $500,000 one time and not $120,000 for this many months in a row.

There are knowledge gaps where physicians aren't so familiar, or nurse practitioners lack understanding of the adverse event management. For referring physicians, discussing neurotoxicity with patients can sound a little scary.

We do run into issues with late referral to CAR T. I had a patient recently who had [progression after] a few lines, and they had bad bowel involvement and high disease burden, so we had to debulk them, but then they passed before we could get them anywhere. Earlier is always better. We can work with you for other therapies. Lack of caregiver support is one that is difficult to get around if they don't have somebody there. I have old veterans who are living on their own, they don't have anybody, and then they're required travel to treatment centers.

How has the FDA’s update on the REMS (Risk Evaluation and Mitigation Strategy) program for CAR T-cell therapy affected patients?

We did just get pretty big news from the FDA, where they're doing away with the REMS programs for CAR T across the board.³ That means not just the lower toxicity products, but every single product [including] axi-cel. You now only need to be within 2 hours of a treating facility for 2 weeks. It used to be 30 days. Two hours is still not very close [for some of my patients]; Pennsylvania is a big state. If it was 5 hours, that would be a long time to be neurotoxic on your way to the hospital. But 2 weeks isn't so bad now, because we used to have to tell patients, we're going to put you up in a hotel…for a whole month, and they say, No, thanks,” but 2 weeks is sometimes palatable, especially if you're going to spend a week or 10 days of that inpatient and then you [stay at] a hotel for a couple days afterward.

If they do live 2 hours away, they're still making that recommendation that they need to [stay], and companies will pay for that. Patients don't like that regardless, even if you say a company is going to pay for it, but 2 hours and then they need for 2 weeks. You have to have somebody looking after you as an outpatient because of the neurotoxicity. It [primarily] occurs during the first 2 weeks. The driving restrictions got reduced to 2 weeks, and that was a huge thing, because it used to be 8 weeks. These requirements went down a fair bit. I think a lot of people are hoping that the removal of some of these will help patients. It'll be a little bit easier on their quality of life and also help other programs pick up CAR T if they don't have to do a lot of these REMS programs and things like that. Hopefully it's just the first step.

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DISCLOSURES: There were no known relevant disclosures.

REFERENCES:

1. NCCN. Clinical Practice Guidelines in Oncology. B-cell lymphomas, version 2.2025. Accessed July 30, 2025. https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf

2. Hoffmann MS, Hunter BD, Cobb PW, Varela JC, Munoz J. Overcoming barriers to referral for chimeric antigen receptor t cell therapy in patients with relapsed/refractory diffuse large B cell lymphoma. Transplant Cell Ther. 2023;29(7):440-448. doi:10.1016/j.jtct.2023.04.003

3. FDA eliminates Risk Evaluation and Mitigation Strategies (REMS) for autologous chimeric antigen receptor CAR T cell Immunotherapies. News release. US FDA. June 27, 2025. Accessed June 27, 2025. https://tinyurl.com/bp5pxxks