The vice president for Clinical Services at OneOncology describes challenges and opportunities for chimeric antigen receptor (CAR) T-cell therapy in the community practice setting.
Three years ago, chimeric antigen receptor or “CAR” T-cell therapy set off a revolution in cancer treatment. Customizing a patient’s own cells to fight certain leukemias and lymphomas offered promise to patients who had run out of treatment options. Soon, FDA is expected to act on lisocabtagene maraleucel (liso-cel), which could offer another choice for patients with large B-cell lymphoma who have failed prior therapies. Liso-cel incorporates a manufacturing process that separates CD8+ and CD4+ T-cells to create a therapy with a defined ratio of each type; results from the TRANSCEND trial show an overall response rate of 73% and a complete response rate of 53%, but with fewer adverse effects from cytokine release syndrome than seen previously.
The revolution of CAR T-cell therapy came with a steep price tag. The first 2 treatments, tisagenlecleucel (Kymriah) and axicabtagene ciloleucel, or axi-cel (Yescarta) reached the market in 2017 at $475,00 and $373,000, respectively. Duncan Allen, MHA, now vice president of Clinical Services for the community oncology network OneOncology, experienced the growing pains of paying for CAR T-cell therapy up close: he served as administrator for one of the country’s very first programs at Vanderbilt University Medical Center in Nashville, which is also the home base for OneOncology.
The American Journal of Managed Care® spoke with Allen recently about bringing CAR T-cell to community practice, where the challenges include guiding patients and families through the financial process and managing the side effects, which can be considerable. (This interview is edited slightly for clarity).
AJMC®: What makes it challenging to bring CAR T-cell therapy into the community practice setting?
Allen: 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, and that can be 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.
AJMC®: Are there any advantages of administering CAR T-cell therapy in the community practice level?
Allen: 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-certified outpatient facility. ... I think that really is a game changer, and really makes the community setting ideal for future CAR generations.
AJMC®: What are the constraints that are holding back growth of CAR T-cell therapy as a primary treatment?
Allen: 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 are going to have address matching price to outcome. And CAR T-cell therapy is at the top of that list.
Lastly, I think last time I looked, there are over 1000 trials for cellular therapies, and many are beginning to be tested on solid tumors. So, 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. And I think the community setting is uniquely positioned to help with that scale.
AJMC®: Can you describe the reimbursement landscape compared with 2017, when the first CAR T-cell therapies reached the market?
Allen: 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 2 years, largely thanks to that advocacy from the American Society for Transplantation and Cellular Therapy, the American Society of Hematology, and other cellular therapy groups. Today, around 90% of plans have coverage for CAR T. But as we know, 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, to the administration of steroids and freezing 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.
AJMC®: Are some CAR T therapies and indications more appropriate for the community setting than others?
Allen: 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 therapies, most folks would say that there have been different experiences with the two primary players. But over time, I think we will have definitively determined 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.
AJMC®: Today community practices are involved in CAR T clinical trials, but can you be more specific about which ones?
Allen: Sure, so I would say, when you look across the national landscape in the community setting, I would say most all major groups that have cellular therapy assets are working with community practices. As I mentioned, I think there are over 1000 trials in cellular therapy. What's most important is that we're identifying the appropriate trials for our patient populations in the community setting, and ensuring that they're offered up to 2 each … There's really availability at the local setting for all those cellular therapies, and that's something that we are very focused on doing and making available to all patients.
AJMC®: Will we be able to see how the community practice patients fare in these trials relative to say, the academic center patients?
Allen: Sure. I think that's something that OneOncology is also uniquely positioned to address. We obviously are very focused on real-world data, on the real-world experience of the patient. For a therapeutic class as young as CAR T therapy, I think real-world data studies are going to be an area of focus not just for community practices, and not just for providers, but also, I think these are going to be things that we see increasingly more mandated by the FDA. And I think the FDA will be really interested in monitoring how those therapies evolve over time. Again, we're only a couple of years out still from the initial administration. I think as we go forward, there will be increasingly more pressure to look at scaling research efforts for CAR T therapy. And I think real-world data will play a large part in that.