Behind the FDA’s Elimination of REMS Program for CAR T-Cell Therapies

On June 26, 2025, the FDA announced the elimination of the Risk Evaluation and Mitigation Strategy (REMS) program that applied to 6 chimeric antigen receptor (CAR) T-cell therapies approved to treat patients with leukemia, lymphoma, or multiple myeloma.¹ Additionally, labels for these therapies were modified in terms of requirements for monitoring, remaining in proximity to the treatment center, and driving vehicles after CAR T-cell infusion.

The REMS program was no longer necessary because of the accumulated experience gained over years of CAR T-cell use post approval. The decision had been called for by groups such as the American Society for Transplantation and Cellular Therapy (ASTCT), which argued the REMS requirements increased barriers to access to vital treatments for patients and created additional burdens for treatment centers that provided CAR T-cell therapies.²

“Over time, we’ve recognized that our transplant and cell therapy community as a whole is able to ensure the safe use of these treatments without these extra requirements placed on top of the use of these treatments as a standard of care for patients,” said Frederick L. Locke, MD, cochair of the ASTCT 80/20 Subcommittee and an author of their review of the recommendations for safe use of CAR T cells.

In an interview with Targeted Oncology™, Locke, chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center in Tampa, Florida, discussed how the REMS program elimination came about and what effects he hopes this will have on patient access to these crucial cellular therapies.

Targeted Oncology: What was the REMS program for CAR T-cell therapies, and how did it affect access to treatment?

Frederick L. Locke, MD: Since CAR T-cell therapies have been FDA approved, going back to 2017 at least, for adult treatment of cancers, there has been something called a REMS program, and this is put forth by the FDA to ensure safe administration of a therapy when it’s approved as a standard of care. In this case, CAR T-cell therapy, the FDA put forth these REMS programs to ensure the safe administration of CAR T, and it included things like education of providers and nurses who cared for CAR T patients and documentation of that education at the treatment centers. It included the need to give a wallet card to patients to ensure they could inform their health care providers that they had received CAR T-cell therapy. It included some requirements of the pharmacy and treatment centers to hold a drug called tocilizumab [Actemra] onsite so they could administer that to patients if they developed complications of CAR T-cell therapy and also reporting of toxicities to the FDA should they occur after CAR T-cell therapy. These REMS programs were put in place to ensure the safe administration of CAR T-cell therapy.

Which patients have been affected most by these limitations on access?

These REMS programs definitely set up some potential access barriers. One of the requirements for some of the programs is that they be seen daily for 7 or 15 days. Even outside of the REMS programs, the FDA labels were saying patients had to remain close to the centers for up to 28 days. They couldn’t drive for 2 months. So that creates some access barriers. On top of it, these REMS programs were burdensome to the treatment centers, requiring training and documentation training and a whole infrastructure around giving CAR T. While some of that’s appropriate, many of those things were already in place at these treatment centers, so [there was] duplication of effort to do these REMS programs, and that, in turn, led to treatment centers not being willing or able to administer all the FDA-approved CAR T-cell therapies because of these additional burdens placed upon the treatment center.

Even smaller centers that were not doing hematopoietic stem cell transplant, which is a cell therapy paradigm that existed before CAR T, weren’t doing transplant. It was difficult for them to get up and running because of these REMS programs. Again, some of this training was necessary and appropriate. But over time, we’ve recognized that our transplant and cell therapy community as a whole is able to ensure the safe use of these treatments without these extra requirements placed on top of the use of these treatments as a standard of care for patients.

Could you discuss the findings that you presented at the ASTCT 80/20 workshop on the REMS program and how to streamline these requirements?

The ASTCT is a society that I’m deeply involved in, and I currently serve as the chair of the committee for cellular therapy. I also serve as the cochair for something called the 80/20 subcommittee or 80/20 initiative that we put together. The 80/20 came from the concept that to…administer these treatments as a standard of care, about 80% of the knowledge we needed programmatically existed at our treatment centers. We were already doing stem cell transplants for patients. We’re already familiar with educating our physicians. So asking us to do these REMS [programs] was, in many cases, duplicative and onerous. [However,] 20% may be unique to the individual cell therapy, and understanding and having the knowledge of that 20% of unique things for each CAR T product was important. So we put together this 80/20 initiative to start to look at places where we could streamline the administration of these treatments…. Initially, we interfaced with the FDA through its cell therapy liaison meeting. That was in December 2022, and we proposed that REMS was onerous, duplicative, and unnecessary.³

The FDA heard our communication to them about these programs and how they could potentially be decreasing access to CAR T-cell therapy. We put together a workshop around the idea of REMS for CAR T-cell therapy, and we got together stakeholders from across the community, including treatment centers, [and] stakeholders from the Foundation [for] the Accreditation of Cellular Therapy [FACT], which is a professional organization overseeing transplant centers and CAR T centers. Independent of these REMS programs, we’ve got the Center for International Blood & Marrow Transplant [Research] [CIBMTR]. They collect data on transplant and CAR T patients and numerous other stakeholders across the board to get [people] to come together and start to think and discuss where we as a society, as treating centers, and as professional societies were able to provide the assurances that these could be done safely for patients. We came up with a white paper about some of the things that were already in place that abrogated the need for this REMS program with CAR T.

By the time we published our white paper, the FDA had already walked back, to some degree, some of the REMS requirements. By July 2024, the FDA was already saying, "We don’t need you to have a wallet card given to patients. We don’t need you to record the training and education sessions for these physicians." Subsequent to that, after we published our white paper, the FDA removed the REMS completely for CAR T-cell therapy administration. By June 2025, there’s no more REMS, and there’s a recognition that we as a community are able to safely administer these treatments to our patients.

I think ultimately this does increase access to the therapy. It allows more treatment centers to open up, to provide CAR T, and allows us to utilize the resources and the infrastructure we already have in place without this added layer of the REMS and FDA oversight of a standard-of-care FDA-approved therapy.

How do you think the experience gained from doing CAR T-cell therapy has built confidence in removing the REMS program?

Tens of thousands of people have received CAR T-cell therapy over the last 8-plus years it’s been FDA approved, and so it’s just been demonstrated that we’re able to manage these patients safely. We’ve seen over time that the rates of severe cytokine release syndrome and neurologic toxicity from CAR T, the rates of severe toxicities, have gone down, and that’s primarily because of earlier intervention. We were able to give immunosuppressive treatments earlier in the course after CAR T infusion at lower grades of toxicities, which helps prevent the onset of those higher-grade toxicities. This is borne out over several years, and a number of investigations have shown that this strategy is viable and the use of tocilizumab and corticosteroids early on does not prevent patients from achieving durable remissions with CAR T-cell therapy. As a community, we’re able to manage these treatments much more safely and, in many cases, now in the outpatient setting. We’re encouraged by that, and we hope to continue to see more and more patients benefit from CAR T-cell therapy moving forward.

How did the elimination of the REMS program come about, and how has that changed the requirements for patients?

That came about through multiple community discussions with the FDA and the FDA’s internal deliberation. At the core of it, these REMS programs are not meant to be forever programs. The idea is to ensure there are some safeguards in place until the community is able to show that they can safely administer these therapies. There have been REMS programs in place for other cancer treatments that have been in place for many years—much longer than CAR T—and have not gone away. We’re encouraged by the fact that the FDA has agreed with us that REMS isn’t necessary. We’re able to administer these therapies safely to patients. We’re able to ensure that our providers are appropriately educated, can treat the complications, and that we’re able to report the toxicities and track those as a community without the need of these REMS programs.

It's a dialogue, and we were happy that the ASTCT 80/20 initiative has played a role in that, but others across the community certainly did as well. At the end of the day, this reduces the administrative burden on treatment centers like ours here at Moffitt Cancer Center. Others across the country are enabled to provide these therapies, because it is additional administrative work that we don’t have to do because we know we can safely give these treatments to patients.

What effect has this had on patient access so far, and how will it continue to affect patient access?

I think that more and more treatment centers will open that can do CAR T. We’ve also started to see patients have the expectation, in some cases correctly, that maybe they don’t need to stay near the treatment center for 28 days. Maybe they can go home sooner than that if they’re coming from afar. That, in turn, reduces the patient’s unwillingness to come and get the treatment if they don’t have to stay for a month. That being said, there are higher-risk patients whom we just don’t feel it’s safe to go far away from our treatment center for 2 weeks after [infusion], but I think the benefit…is that we have more flexibility to treat patients appropriately.

Ultimately, the reality is that not enough patients who could benefit from CAR T-cell therapy are being referred to get CAR T-cell therapy. We just need to get the word out. We need referring physicians to understand that the data unequivocally show that CAR T-cell therapy leads to better outcomes for patients than alternative treatments, including bispecific antibodies going after the same targets. We need patients to be referred to CAR T treatment centers. We need to open more CAR T treatment centers so that the people who could benefit from this treatment are getting it. It’s unfortunate, but in the United States, only about 20% or 30% of the patients who could benefit from CAR T-cell therapy are getting it, and I think a big part of that is barriers to referral and also the fact that patients have to travel to these treatment centers. We need more patients to benefit from these therapies.

Do you often see patients who have more difficulty getting access to CAR T-cell therapy?

I think each region is different. But at Moffitt Cancer Center in Tampa, we have by far the largest CAR T program in the state and, in fact, in the entire Southeast. We get patients from all over the state of Florida. We get patients from Georgia, Alabama, and we get international patients. There are other CAR T treatment programs available in the state, but they may have capacity issues or other barriers to seeing patients. Our doors are open, and we continue to see patients seeking out CAR T. Again, a bigger concern of mine is that patients who could benefit are not even being considered for CAR T, and we really want patients to benefit from this treatment.

What research is being done to help streamline the safe administration of CAR T-cell therapy?

There’s a lot of work looking at outpatient administration of CAR T. There are a number of FDA-approved CAR T-cell therapies, and they have different toxicity profiles, and so the safety or the expectations for giving an outpatient [administration] are different across those different treatments for different diseases, but we have a robust outpatient CAR T program here, and we certainly prefer to do it outpatient when we can. That increases access, not necessarily because we can do more outpatient but because patients are more willing to come and get CAR T if they recognize that it doesn’t require a prolonged hospitalization in every case.

We’re very proud of our role in in the removal of REMS for CAR T-cell therapy, and it couldn’t have been done without the support from my cochair, Dr Sarah Nikiforow, and all the other sponsorship and participation we’ve had from members of ASTCT, FACT, CIBMTR, and numerous other organizations.

REFERENCES

1. FDA eliminates Risk Evaluation and Mitigation Strategies (REMS) for autologous chimeric antigen receptor (CAR) T-cell immunotherapies. FDA. June 26, 2025. Accessed October 24, 2025. https://tinyurl.com/yu46ysuw

2. Locke FL, Mahmoudjafari Z, Kebriaei P, et al. Awakening from REMS: ASTCT 80/20 ongoing recommendations for safe use of chimeric antigen receptor T cells. Transplant Cell Ther. 2025;31(6):349.e1-349.e12. doi:10.1016/j.jtct.2025.02.009

3. Locke FL. Development of a sustainable risk mitigation strategy: standardization of risk evaluation and mitigation strategies and sunsetting of REMS for CAR T cell therapies. Presented at: 2023 FDA Cell Therapy Liaison Meeting; December 5, 2022.