Delays Mean Some Miss Window for CAR T-Cell Therapy, Cardinal Health Data Show

When a physician makes the call that chimeric antigen receptor (CAR) T-cell therapy offers the best chance for survival in patients with relapsed large B-cell lymphoma, there isn’t time to spare. But data gathered over the past 2 years by a team from Cardinal Health Specialty Solutions revealed roadblocks community oncology practices encounter when trying to navigate payer approvals for CAR T-cell therapy are among the barriers that cause patients to run out of time—and this situation isn’t improving.^1,2 The most recent round of data was presented in December during the 62nd Annual Meeting and Exposition of the American Society of Hematology (ASH).²

With new CAR T-cell therapies in the pipeline—including treatments that promise less toxicity and new therapies for multiple myeloma—the findings raise concerns that disconnects among payers, providers, and patients could stall this life-saving treatment.

Data from hematologists/oncologists were gathered a year apart, first in February 2019 and then during the period of November 2019 to February 2020. The initial survey covered 59 physicians, who were all in some type of community practice; the second included 168. Each time, the share of patients referred for CAR T-cell therapy who were unable to receive was almost one-third. “High cost and toxicity continue to be potential deterrents to CAR-T consideration and appear to be increasing in significance,” the authors concluded.

For insights, The American Journal of Managed Care® (AJMC®) spoke with lead author Ajeet Gajra, MD, FACP, vice president at Cardinal Health, about identifying and removing the barriers for offering CAR T-cell therapy at the community practice level. The interview is edited for clarity.

AJMC®: It's normal for to have challenges with payers when a new therapy is approved. But your findings show that the percentage of patients who have been unable to receive CAR T-cell therapy after referral was about the same nearly a year apart, with the second survey coming more than 2 years after approval. What accounts for this?

Gajra: These are complex therapies—they are essentially living cells derived from, engineered, and to be used as therapy for a particular individual. Obviously, they are challenging in terms of logistics, and there’s also the cost factor. The issues are twofold. One rests with the providers: they need to be very clear in terms of who they're referring for CAR T therapy. The labels are very explicit—2 prior therapies and progression, and also in terms of medical comorbidities. This is not just something that you can try as CAR-T therapy needs planning and following each step of a detailed process. The other piece is, as we all know, with payers, there's a complex prior authorization process. For some of these patients, it can be daunting for the managing team to collect all the information needed in a timely fashion to satisfy a payer’s requirements. That would include the diagnostic biopsy, and the history of therapies and regimens received thus far, [whether] they've had bone marrow transplant—the payer would need those records. If care has been fragmented—especially if the patient was treated at another facility, or say, a tertiary center where they went for care or a transplant—all that information has to be populated. That is a potential barrier, which leads to delays. Diffuse large B-cell lymphoma is not the disease that you can temporize with simple measures. If it's recurring a third time, these patients tend to be quite ill. A delay of a week or two sometimes can force the hand of the provider to go an alternative route, because they feel “My patient is deteriorating, I still don't have the authorization, what am I to do?” And they have to craft an alternative plan. So, we may be capturing some of those issues when it comes to factors leading to delays. So, there are patient factors, provider factors, and payer factors, which [contribute] to these delays.

AJMC®: As you noted, the payer delays can lead to the to the patient not receiving the therapy at all. Do providers need more support to navigate the process, whether it would be from a professional organization or from the manufacturers themselves?

Gajra: Absolutely. I feel strongly that additional support would be valuable. We found that most providers thought that they are quite well-versed with the science behind CAR T. But many of them may still not be aware of the complexity of the process involved in getting a patient on to CAR T and then managing them afterward. I feel it still starts with education—you don't want to refer the wrongpatients, because ultimately, they're going to go through the rigmarole and not end up getting the treatment, which is also something we captured where patients were being referred to CAR T centers, but ultimately not getting the treatment. So, there is that piece.

Second is support, support, support. We have these results while we had only the 2 CAR T products as of the summer of 2020. We now have 3 CAR T-cell products approved—with 1 for mantle cell [lymphoma]. CAR-T therapies are to be administered at designated CAR T centers, and but about 1 in 6 providers didn't have a CAR T center in their geographic vicinity, which is a barrier. Also, there's a question of, can there be reciprocity? Must each center be approved for every therapy that they're going to administer? That’s a piece that manufacturers can help with. Patient support and access services sponsored by pharma companies can help with streamlining the prior authorization process, to expedite how quickly patients can check all the boxes—get all the i's dotted and the t's crossed so that they can be at least evaluated sooner. Hopefully, patients can be approved by the payer sooner when appropriate, to move to the next step.

AJMC®: We talked about toxicity as being one of the big challenges with CAR T-cell therapy--that's been the case from the time it was approved. Is this a bigger challenge at the community level—in terms of the patient who's more concerned about the looming threat of CRS? Or is it more the provider who has the concern? Or is it a combination?

Gajra: It’s a great question. I certainly agree that the specter of toxicity is still [quite] strong, and that community practices have a lower threshold or a greater concern for toxicity than the academic centers. This has come out loud and clear at [live meetings] when we engage with providers, [which are] often includes a mix of largely community oncologists, but also some academic representatives as well.

Patients are concerned, but for the most part, with appropriate counseling, most patients are willing to receive therapy because they realize they are running out of options. I would also highlight is that as the field evolves, there have been remarkable improvements in the management of toxicity, so a lot of it can be mitigated and managed early. The thresholds have improved in terms of identifying CRS, but also neurotoxicity, which can be quite scary and devastating.

When we look at a scientific literature, there's definitely improvement in management of toxicity especially now with real world use of CAR-Ts being reported. Patients for the most part can be quite eager to receive what many of them would probably perceive as lifesaving and/ or significantly life-prolonging therapy. But [it’s a different challenge] for community physicians, especially those that are not attached to a large tertiary care hospital. They don't have immediate access to critical care—to an [intensive care unit] ICU. If your patient’s health is declining, they are going to land in the ICU. There's been a lot of work [done] on the disparities in rural settings or smaller communities, and I think there's definitely more apprehension with these therapies in the smaller, more remote practices.

AJMC®: In data that you presented at ASH, the emergence of the cost factor as a barrier is very apparent in the second round of data collection. What accounts for this?

Gajra: We learned from our initial work that cost was a major concern in the minds of the treating oncologists. Thus, we decided to reassess as a follow up: This was a larger sample size than in [the first survey], and was 2-plus years post-approval of the initial therapies. And the research showed that aside from intake and toxicity concerns, cost remains a major barrier or major concern in the minds of the providers [due to gaps between the treatment list price and reimbursement rates, especially from Medicare]. That gap has perhaps never been completely bridged. … From what we know the [list price] is about $373,000 for treatment. Certainly, attempts have been made with NTAP, the New Technology Add-on Payment [in Medicare], to reduce that burden, [and not rely on hospitals] where majority of CAR-T is being administered to just supplant the funding for the facilities. It cannot be denied that it is still a very high cost therapy.

Some of this cost sensitivity may arise from the fact that providers are looking at longer term outcomes. If providers are [committing] to a complex process and an expensive therapy, then do the outcomes bear that out? Especially if there are a lot of early failures of therapy, then perhaps, this is a barrier.I don’t have evidence for this,but it has been brought up by providers during discussion at live meetings on the subject as a possible barrier.

In my mind, if there was a greater confidence in being safely able to administer these therapies in the clinic versus in the hospital, I think there will be greater interest in these therapies. Because otherwise, it's really the hospital that's sort of bearing the cost. Whereas if you do it as an outpatient infusion, then it becomes a proposition for the practice, given that it's a very expensive infusion…. The community practice planning on outpatient administration has to assess the risk of the patient getting sick and getting admitted for toxicity. But as we learn more, community oncologists will become more confident about preventing toxicity and ensuring that they can safely administer these treatments on an outpatient basis. I think that's where the future is. And I think that will really help CAR T-cell therapies take off.

AJMC®: You mentioned the gap in Medicare funding. How does this compare with reimbursement for patients with commercial coverage?

Gajra: I think this is one of the questions [for which] we don't have an answer yet. We haven't teased that out. And that's just the honest truth. That wasn't part of what we've surveyed thus far. I believe that this question will be more suited for CAR-T centers performing the actual infusions.

AJMC®: Fair enough. I’d like to ask about coronavirus disease (COVID-19). It would seem that during the pandemic there would be an interest in not keeping patients in the hospital any longer than necessary. COVID-19 emerged since you gathered your information, but I'm wondering what it’s been like since then—does the pandemic make it favorable to administer CAR T-cell therapy in the community setting?

Gajra: Absolutely. We’re actually redoing the survey as we speak. And, we hope to get a decent sample size of current practices; we wanted to redo it in the context of the fact that we now have 3 products approved. And, hopefully in 2021, we'll see more CAR T therapies coming down the pike, as some data are looking really good coming out of ASH 2020. There seems to be anecdotally a lot of interest, especially amongst the larger practices, in terms of taking on outpatient infusion of CAR T cell therapies, especially among practices which are geographically close to a hospital setting. And we certainly got that during our discussion the last time, which was, admittedly in the springtime. So, we're trying to recalibrate that and see if that change has actually transpired. …

[COVID is a driver for outpatient care] for everything, including CAR T. We must recognize that with the initial 2 products, one of them implied in the label that it should be given in the hospital, which is not the case for the other product. So, I feel that the labelling or the implications of the label also impact practice. As we see new products emerge, if there's no direction that they should be given in a hospital, I think that will encourage the use of these therapies in the outpatient setting. But the COVID pandemic, as we all know, has been a driver to push care away from the hospital and into the clinic.

AJMC®: We've covered a lot of ground. Is there anything that we didn't cover that you'd like to add?

Gajra: First of all, even though now it's been 3-plus years since the original approval, there is still room for educating and keeping the community provider especially engaged. It’s not every day or every other day that a community provider will have the opportunity and will have the appropriate patient for a CAR T-cell therapy. It’s not like hormone-positive breast cancer that they're seeing every day of their life. So, I think, as more and more indications become amenable to CAR T therapy, that ongoing engagement with be essential from the manufacturers, from organizations, or from AJMC—whatever avenue there is.

Number 2, is the prior authorization process. Streamlining that process for the appropriate patient is so critical, and anything that can be done to simplify that facilitate that, both from the payer perspective and the manufacturer side would really help drive this therapy further. And then third, perhaps manufacturers can help identifying the pain points at the CAR T centers. These are typically large academic or tertiary care cancer centers. We’ve encountered concerns from community oncologists such as the patient was referred for CAR T, but was ultimately treated with a transplant, or a finite percentage of patients never ended up getting CAR T at the CAR T center, or that there wasn't adequate communication in terms of what should the community provider do when the patient returns after CAR T cell therapy.

We’ve heard that the intake of the CAR T was so slow. So here you have a patient, you’ve moved heaven and earth for prior approval authorization, and you referred them but then they couldn't get in or it took too long. So, I think that is another area where we can shave some time off in terms of getting the patient in line for CAR T.

Another potential barrier to CD-19 directed CAR T therapies in LBCL is the recent approval of tafasitamab (Monjuvi), a CD-19 directed monoclonal antibody, which is easy to give in the office and technically targets the same antigen. What is not known clearly is whether prior exposure to tafasitamab leads to impaired response with CAR T-cell therapy and vice versa.

One other thing that we learned is, and I think the community physicians are learning this as well, is that patients are likely to need bridging therapy while they are awaiting CAR T-cell therapy. In the early days, they were sort of taken aback like oh, “What am I supposed to do now? You're not going to have your product for another 6-8 weeks?” But you know, now they're learning that there has to be something else to hold the disease i.e., bridging therapy while awaiting the CAR T product, so it’s really a multipronged approach. And I feel manufacturer, CAR T center, provider, and the patient, and then the payer, are in it together and little tweaks can streamline the process somewhat better than it is now.

References

1. Gajra A, Jeune-Smith Y, Kish J, Yeh TC, Hime S, Feinberg B. Perceptions Perceptions of community hematologists/oncologists on barriers to chimeric antigen receptor T-cell therapy for the treatment of diffuse large B-cell lymphoma. Immunotherapy. 2020;12(10):725-732. doi: 10.2217/imt-2020-0118

2. Gajra A, Hime S, Jeune-Smith Y, Feinberg B. Adoption of approved CAR-T therapies among US community hematologists/oncologists. Blood. 2020;136(suppl 1):34-35. https://doi.org/10.1182/blood-2020-141990