The Fast Pace of CAR T-Cell Innovation Caused an Array of Challenges in Treatment

The evidence shows that chimeric antigen receptor (CAR) T-cell therapies are effective, but the price tags on these treatments are high and have raised concerns about how many patients will get treated. During a discussion at The American Journal of Managed Care^®’s Patient-Centered Oncology Care^® meeting, held Friday in Philadelphia, panelists outlined the efficacy of the 2 FDA-approved therapies, Medicare reimbursement for CAR T-cell therapies, and the pace of innovation in healthcare.

In children, tisagenlecleucel (Kymriah) has successfully treated children and young adults, up to age 25, with relapsed or refractory acute lymphoblastic leukemia, explained Shannon L. Maude, MD, PhD, assistant professor of pediatrics in the Division of Oncology at the Children’s Hospital of Philadelphia, and medical director of the Center for Cellular Immunotherapies at the University of Pennsylvania Perelman School of Medicine.

In the trials that led to FDA approval, patients treated with tisagenlecleucel had a remission rate of 81% after relapsing more than once after the best standard of care. In some of the longer-term data now being seen, patients who went into remission have a relapse-free survival rate of 66%.

The other FDA-approved therapy, axicabtagene ciloleucel (Yescarta), is indicated in adults with diffuse large B-cell lymphoma (DLBCL), which typically affects people in their 60s and 70s, said John W. Sweetenham, MD, FRCP, FACP, FASCO, professor of medicine and associate director of clinical affairs at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. For 15 to 20 years, treatment for disease has be relatively the same: chemotherapy is front line followed by a bone marrow transplant. But if those 2 treatments are unsuccessful, the patients had essentially no other options.

Now, there have been extraordinary responses with CAR T-cell therapy, he said. There are patients who, in the past, he would have anticipated have a bad outcome after relapsing, who have now survived more than a year after treatment.

“This treatment is like nothing we’ve ever seen before in terms of its ability to turn very sick people around,” Sweetenham said.

However, since these therapies are so different, there are still plenty of unknowns. There have not been any randomized trials to compare the CAR T-cell therapy treatment with more standard treatments, for instance.

As a result of how successful CAR T-cell therapies have been and the uniqueness of them, they cost upwards of $373,000 per treatment—the good news, said Erika Miller, JD, senior vice president and counsel at CRD Associates, is that patients only need the treatment one time. The problem is that regulators and legislators are concerned about safeguarding the Medicare trust fund, and these therapies are a big hit, financially.

There is concern that if Medicare pays the full cost, that it “is sending a signal” to drug makers that the price tag is not a problem and they might even be able to ask for more for the next treatment.

“[Regulators and legislators] are concerned about how many patients are going to get this,” Miller said. “They’re afraid of a tsunami. And then, this is all happening at the same time that everyone in Washington [DC] is talking about the price of drugs.”

She echoed Sweetenham and Maude’s comments that everyone is still waiting to see how effective the treatments will be in the long term. In addition, a greater concern is that there are other CAR T-cell therapies in the pipeline, which will only add to the costs.

“Medicare doesn’t change on a dime,” she said. “It takes them a long time to change their policy. They have mechanisms for payment that have been in place for a long time that they are reluctant to change.”

The pace of innovation has been, perhaps, too fast. It has outpaced changes in payment, but also, “in some ways, we’re ahead of the evidence,” Sweetenham said.

“We don’t want to end up in a situation where patients are potentially missing out on effective treatment because it’s taking us too long to get the evidence that we really need,” he added.

Putting together clinical trials is complicated and expensive, and researchers need a solid partnership with all the stakeholders in terms of getting needed clinical trials moving, Sweetenham said.

Maude added that when trials are set up, they need to be optimized so we can identify which patients will benefit the most from CAR T-cell therapies and, thus, improve the outcomes that are already seen. There is additional cost in setting up those types of trials, but they will be more cost effective in the long run, she said.

Moving forward, improving patient access to these treatments is critical, Miller said. The cost of CAR T-cell therapies is so high that academic medical centers are losing out on more than $100,000 for each patient treated. As a result, there are some centers that are deciding not to offer CAR T-cell therapy.

Maude and Sweetenham also highlighted the access challenges. Since so few centers offer CAR T-cell therapy, patients often have geographic barriers and have to drive long distances in order to get treatment. Patients who have commercial insurance tend to have less trouble getting the treatment approved than patients who are in Medicare.

While the current administration has been reluctant to pay the full price tag for these therapies, it has shown it is very focused on promoting innovation, Miller said. “There’s recognition that there’s innovation here that can’t be choked off,” she said. The administration is listening, and there has been some progress with the increased new technology add-on payment, but with an election next year, there could be a new administration in the White House with a different perspective.

When asked to peer into the future, Miller predicted that there would be a payment model for CAR T or cellular therapies being tested. Next year there might be a CAR T-cell therapy for multiple myeloma, which has a large patient base, so there will be more pressure on CMS to create a payment model.

Maude and Sweetenham are both hoping to see more longer-term follow-up data and better predictions about which patients will benefit the most. Sweetenham is also anticipating that these treatments will move more into the outpatient setting and hopes to see patients getting better access to the treatments.

“Pessimistically, I haven’t seen the field really move that far in 5 years,” Sweetenham said.