Although clinical responses have been remarkable and the approval by the US Food and Drug Administration (FDA) of these novel therapies was heralded as the biggest medical news of last year, it appears that chimeric antigen receptor (CAR) T-cell therapy has been used in only a small number of patients since they came on the market.
A big stumbling block has been the high cost and reimbursement problems for the novel therapies. But the clinical responses are far superior to anything that has been seen before.
"When you see data like that, it becomes ethically challenging for people to say that we can't do this because of financial issues," one expert told Medscape Medical News.
Two CAR T-cell therapies has now been approved in the United States ― tisagenlecleucel (Kymriah, Novartis), for certain pediatric and young adult patients who have a form of acute lymphoblastic leukemia, and axicabtagene ciloleucel (Yescarta, Kite/Gliead) for adult patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma who are ineligible for autologous stem cell transplant.
Both have eye-wateringly high price tags ― $475,000 and $373,000, respectively.
This has been causing problems in getting these products to eligible patients. Snags in reimbursement have been blamed for holding up treatment.
At the 15 cancer centers in the United States that have been authorized thus far to administer CAR T-cell therapy, only a handful of patients have been treated. At least 200 others remain on a waiting list, according to a recent Bloomberg article.
"The biggest issue has been insurance, particularly with Medicare and Medicaid," said Michael Bishop, MD, director of the cellular therapy program at the University of Chicago Medicine, Illinois, who was quoted in the article. "There's no billing codes for this. It's been difficult, to be very blunt."
In addition, related costs can also push up the price of this therapy. For example, treatment carries a high risk for toxicity, which can necessitate management in the intensive care unit. The overall cost of this therapy could reach $1.5 million per patient, one expert estimated.
Holdups With Medicare
As previously reported by Medscape Medical News, reimbursement for CAR T-cell therapy is a complicated issue, primarily because the therapy is so new and is basically unchartered territory for payers. This is not a "typical" therapy from the point of view of cost structure, even compared to leukemia induction or stem cell transplant.
But the main problem is with the Centers for Medicare & Medicaid Services (CMS) and private carriers that use a uniform coding system. Dealing with CMS can be particularly challenging, owing to the complexities of their reimbursement system, which relies heavily on a fixed coding system and calculations for determining payment. This will be problematic for institutions that plan to treat patients with CAR T-cell therapy, because about 50% of the lymphoma patients who eligible to receive axicabtagene ciloleucel will be Medicare beneficiaries.
Gary Goldstein, business manager, Blood and Marrow Transplant Program, Stanford Health Care, in California, noted that from a medical perspective, most of the commercial insurance companies have been relatively quick to embrace the medical appropriateness of this treatment, "at least for those patients who meet the strict FDA guidance," he said.
But Medicare has a different process, and "unfortunately, everything with Medicare takes time," Goldstein told Medscape Medical News.
Although these drugs are very expensive, many feel that the cost is reasonable, given their efficacy. Most of these patients have no other treatment options, and for those who respond, CAR T cells eradicate all traces of the disease after a one-off treatment.
"If you look at other treatments and see how effective this can be, most people in the know don't think they are overcharging," Goldstein commented. "But that really isn't the question from our end."
As a medical provider, Stanford Health Care must purchase the products and then must recoup not only that expense but also the expenses incurred in the collection of cells, the chemotherapy, and patient admission, if that is required— all of which adds up to a significant amount. "Commercial insurers have stated that they understand that we need to get paid for the cost of the CAR T-cell product plus normal reimbursement for a hospital stay and physician care," Goldstein explained.
But Medicare is different. It has its own internal formulas for figuring out what a therapy should cost. Part of that process involves a review of the past history of similar claims. "But that process doesn't work well or work at all on a new technology," he said. "You can't look back 2 years on CAR T cells because they weren't available. Although since they know what these drugs cost ― in theory ― they probably could come up with something sooner, but unfortunately, that is not part of their normal process.
"We would encourage CMS to figure out a way of speeding up the process for important scientific breakthroughs," he added.
Goldstein emphasized that it's not only Medicare that is having problems with coding. "In order for a hospital to bill insurance, we need what we call a J-code, and we can't get a J-code until FDA approval," he said. "So the system itself really adds in a lot of hurdles. Since J-codes are not always assigned immediately, this can create confusion for medical billing."
Overall, the coding process needs to be updated and speeded up, not just for the drugs but for the overall treatment. "We need a specific code for collecting the cells and reformulating them to CAR-T status, for example," he pointed out, "And that doesn't exist right now."
The American Society for Blood and Marrow Transplantation has been leading a group effort to try to standardize coding. It recommends using unlisted procedure codes when a specific code doesn't apply. "But the problem is that when you have an unlisted procurement, Medicare doesn't have a formulary for dealing with that," he pointed out. "And even commercial payers don't have a formulary for that."
Goldstein explained that at Stanford Health Care, they are managing to work around these coding problems with commercial payers. "We have a very small population right now, and they are willing to work with the hospital on a one-on-one basis for each patient," he said. "And as long as we are all in agreement, it doesn't matter that there is an unlisted code, but Medicare doesn't have that flexibility."
For now, this system will work, but it will become more problematic as the number of patients increases, including the number of patients with Medicare coverage. "When we first began doing stem cell transplantation, there was more time to get coding in place, but to this day, reimbursement remains an issue with Medicare, and the growing elderly population eligible for transplant has become a problem," he said. "A bill was recently introduced in Congress that aims to address this, so we will have to see how this plays out."
Waiting Lists and Delays
Because medical centers have to purchase the CAR T-cell products at full cost from the manufacturer, some are waiting for a payer guarantee of reimbursement before moving ahead and treating the patient. Others, like Stanford Health Care, are working with insurers on a case-by-case basis.
At the University of Texas MD Anderson Cancer Center in Houston, more than 100 patients are on a waiting list for treatment. So as not to hold up treatment, some patients have signed waivers indicating that they will be responsible for the costs if insurance doesn't pay.
But as of now, MD Anderson doesn't have a clear policy about reimbursement. "We are still working through the process of negotiations regarding insurance payment. which is still very much in the early stages," said Ron Gilmore, program manager in the Public Relations Office.
The Mayo Clinic, Rochester, Minnesota, is another facility that has been certified for CAR T-cell therapy. They are also trying to get through the reimbursement tangle. "It is something we are trying to figure out at our institution, and as a clinician, I'm reaching out to other clinicians to find out what they are doing at their own facilities," said Yi Lin, MD, PhD, who heads up the CAR T-cell therapy service.
She noted that there are at least 50 patients on the waiting list at Mayo. The list would have been longer except that some patients went ahead with alternate treatments. "Their physicians were concerned about the delay, so if there was something else to offer them, they did," Dr Lin explained.
But for some of the patients, there are no options. As a result, some fell off the waiting list because they died while waiting for FDA approval and for the process to be worked through.
"We had reached out to and had conversations with the major payers as this was going through FDA approval, but the insurance companies are also trying to get more information from us," she said. "We don't have a finalized full plan in writing at the current time, but until we have that, the insurers will review each patient on an individual case-by-case basis until we have a formalized process."
This process is less than ideal, and it can cause delays in treatment. "We can go through the usual process for reimbursement, but then they come back and may want more information, and there may be additional conversations with their medical director and our oncologist — a lot of back and forth," Dr Lin said. "It just isn't as simple as it is for other things, where you pick up the phone and make the request."
Dr Lin explained that to date, their institution has not had to deal with Medicare coverage. "We have not gone through that process yet," she explained.
In conversations with other centers, Medicare's response has ranged from saying it won't reimburse costs because durability of response has not been shown to saying it will approve it, but the potential loss to the facility would be unknown, owing to the amount Medicare will pay.
"This is a huge concern from a public health standpoint because this is an elderly population with lymphoma," said Dr Lin. "Even though we don't have much data on durability, and we recognize that only hundreds rather than thousands of patients have been treated, this treatment is a breakthrough. When we look at the percentage of patients who have responded, and at this advanced stage of disease, it has been better than any other option available.
"It would be terrible for a patient not to be able to get the treatment because of the insurance logistics," she added.
Challenging for Kids Too
Pediatric patients who are eligible for treatment with tisagenlecleucel are facing some of the same issues. Michelle Hermiston, MD, PhD, an associate professor in the Department of Pediatrics (Pediatric Hematology/Oncology) at the University of California, San Francisco (UCSF), told Medscape Medical News that they are in the process of getting authorization to treat their fifth child with CAR T-cell therapy.
"Every child has had a different insurance provider, so it has been interesting," she said. "I feel fortunate that the medical leadership at UCSF has been very receptive to the importance of this therapy, that is potentially lifesaving for these kids. And we have ultimately been able to treat each child."
Dr Hermiston explained that the challenges center around the therapy being so new, and there has been stress because of potential delays. "What I understand from my colleagues around that country is that I'm pretty lucky in that our administration has been very receptive to those stresses," she said. "If anything, I think it's good that this was approved first in children. From an administrative/financial standpoint, people are a little more receptive to the impact of this therapy when the patient is a child.
"We can leverage that a little bit," she pointed out. "But it's been challenging, no doubt about it."
Dr Hermiston emphasized that the data for this population are impressive, even though CAR T-cell therapy is still very new. "The first patient treated is only 5 and a half years out — but we're seeing response rates in the 90% range and extended response in the 60% to 70% range," she said. "So when you see data like that, it becomes ethically challenging for people to say that we can't do this because of financial issues."
"That's the approach we've taken at our institution, and so far its worked quite well," she noted. "A lot of phone calls and emails, but it's worked. And it will get better as we go forward."
One of the patients treated was in his early 20s. He was covered by Medicare. All aspects of his care were reimbursed by Medicare except for the cost of the drug. The hospital was able to obtain it for him free of charge from Novartis through the company's compassionate use program.
Dr Herminston notes that they have also had a patient with MediCal coverage, which is California's Medicaid program, and CAR T-cell therapy was also covered. "But insurance authorization does not equate to reimbursement, so at UCSF, we are going to have to eat the cost for half the patients on MediCal, and that is an issue," she emphasized. "I know that renegotiations are ongoing, but it hasn't precluded treatment, because we are a state-funded institution, and our mission is to treat everyone.
"Children don't choose their parents, so its random luck if you happen to have parents with good insurance," she noted. "So we have chosen at this time to treat patients with limited resources."
It remains an open question as to how long this will continue and how treatment can be made financially viable. "But at this moment in time, I've been able to treat all of the kids that have come my way," added Dr Hermiston.
Medscape Medical News © 2018
Cite this: Few Patients Get CAR T Cells Because of 'Insurance Snags' - Medscape - Jan 11, 2018.