Bringing CAR-T Cell Therapy to the Community

When FDA approved Kymriah (tisagenlecleucel), the first CAR-T cell therapy, in August 2017, then-Commissioner Scott Gottlieb, M.D., heralded the arrival of “a new frontier in medical innovation,” which offered hope of treating the deadliest cancers. But with that early promise came problems, some because the therapy was on the steepest pitch of the learning curve. Kymriah was complex to administer. Patients and caregivers were required to stay in a nearby hotel and hospital stays of a week or more were common. Some patients suffered cytokine release syndrome, a torrent of the immune system’s signaling proteins that results in a raft of symptoms — fever, nausea, rashes — that in extreme cases can be fatal. And there was the then-shocking price of $475,000.

But now CAR-T cell therapy might have reached a new phase when it is no longer solely in the province of academic health centers. More therapies in the class have been approved and are on the market. Shortly after giving Novartis’ Kymriah its blessing, the FDA approved Gilead’s Yescarta (axicabtagene ciloleucel) for relapsed or refractory large B-cell lymphoma. In July 2020, the agency approved a third CAR T-cell therapy, Gilead’s Tecartus (brexucabtagene autoleucel) for relapsed or refractory mantle cell lymphoma, and it may soon approve a fourth, Bristol Myers Squibb’s liso-cel (lisocabtagene maraleucel), which would also be for treatment of large B-cell lymphoma that hasn’t responded to previous treatment. Liso-cel seems poised to enter into community oncology practice, partly because its manufacturing process separates CD8+ and CD4+ T-cells and creates a therapy with a set ratio of CARs.

Duncan Allen, M.H.A., vice president of clinical services for OneOncology, a network of 170 community oncology practices headquartered in Nashville, Tennessee. Allen previously managed one of the nation’s first CAR-T cell therapy programs at Vanderbilt University Medical Center in Nashville.

Managed Healthcare Executive® spoke with Allen recently about bringing CAR-T cell therapy to community oncology practices.*

What are the challenges of bringing CAR-T cell therapy into the community practice?

The emergence of the immune effector cell therapeutic class in general — and specifically CAR-T, the most successful therapy in that class today — has been groundbreaking for patients suffering from specific hematologic malignancies.

Where the challenge lies with CAR-T therapy is that the scientific data is relatively new, and this presents some challenges when trying to determine how these half-million-dollar, cutting-edge therapies should be thought of in relation to their therapeutic peers.

In addition, the therapy brings certain manufacturing complexities. It requires two weeks or more to make. There are specific toxicity considerations that require the use of a specialized steroid, which costs upwards of $2,000 per administration. And, quite frankly, this is a very resource-intensive treatment process that requires intense monitoring of the patient for over 30 days.

There are a significant number of challenges in the current generation of CAR products, but I do see that changing over time.

Are there advantages of administering
CAR -T cell therapy at the community practice level?

Absolutely. CAR-T administration is largely in its infancy in the community setting. As this therapeutic class evolves from our current generation of CARs into future generations where you may have (allogenic) off-the- shelf products, the advantages of administering and monitoring in a community setting are relatively straightforward. There’s access to timely administration and convenience in close-to-home treatments, which I think is very important given the level of monitoring required and the ability to administer in a REMS (risk evaluation and mitigation strategy)-certified outpatient facility. I think that really is a game changer, and really makes the community setting ideal for future CAR generations.

What is holding back the growth of CAR -T cell therapy as a primary treatment?

Many of the initial barriers to reimbursement and administration have begun to be addressed after intensive efforts to push for payment out of CMS. I think there are still many questions about how to sustain coverage for CAR-T cell therapy given the price tags.

With the advent of value-based care, a core tenet of OneOncology, we’ve seen that we must address matching price to outcome — and CAR-T cell therapy is at the top of that list.

I think last time I looked there are over 1,000 trials for cellular therapies, and many are beginning to be tested on solid tumors. We’ll have to think ahead about the scalability of cellular therapy, should solid tumor come into play in the future, so we can ensure that patients have access to these cutting-edge therapies. I think the community setting is uniquely positioned to help with that scale.

How does reimbursement today compare with reimbursement three years ago?

As someone who personally has sat with families and walked them through the reimbursement journey for CAR-T, I can tell you that it has gotten much better. .

There were periods where patients simply would be waiting on their payer to cover their therapy. Luckily, I think we’ve seen the maturation of the coding and reimbursement environment over the past two years, largely thanks to that advocacy from the American Society for Transplantation and Cellular Therapy and the American Society of Hematology. Today, around 90% of plans have coverage for CAR-T.

But they’re still nuances. For starters, it’s not just about the cost of the therapy, but the associated costs for delivering a therapy, including leukapheresis, the administration of steroids and other related costs. The coding considerations have not been inclusive of the full cost surrounding CAR therapy and this has been presented in a number of forums. But it impacts patients and providers and practices, and I would like to see this improve over time as cellular therapy becomes mainstream. I think with increased policy advocacy, we can definitely get to a healthier state.

Are some CAR -T therapies and indications more appropriate for the community setting than others?

As different products are tested, there will be clear winners that are more suitable for the community setting. And those will likely (be) therapies that have lower toxicity profiles, so that you can ensure you’re not going to have to admit your patient to the hospital.

With the current generation of CAR-T therapies, most folks would say that there have been different experiences with the two primary players. But over time, I think we will definitively determine which immune effector cells are more appropriate from an outpatient perspective and which are more suitable for inpatient administration.

So I think the verdict is still largely out.

*This transcript has been edited for clarity and length.