Speculation Mounts About Price Tag for Emerging CAR Therapies

Chimeric antigen receptor (CAR) T-cell therapies could spawn a new and lucrative industry in anticancer immunotherapy, resulting in single-infusion treatments costing hundreds of thousands of dollars, and even attracting medical tourism from abroad, where regulatory permissions are likely to come more slowly than in the United States.

Andrew L. Pecora, MD

Chimeric antigen receptor (CAR) T-cell therapies could spawn a new and lucrative industry in anticancer immunotherapy, resulting in single-infusion treatments costing hundreds of thousands of dollars, and even attracting medical tourism from abroad, where regulatory permissions are likely to come more slowly than in the United States.

That is the picture that is emerging in interviews with oncology experts as the FDA considers whether to approve the first genetically engineered T-cell therapies. CAR T-cell therapies are a new form of immunotherapy treatment that not only breaks fresh ground on innovation in medicine but also tests the boundaries on what patients and payers are willing to pay and what doctors and medical institutions are willing to charge.

In July, the FDA’s Oncologic Drugs Advisory Committee unanimously recommended that the agency approve Novartis’ tisagenlecleucel (CTL019) for the treatment of pediatric and young adult patients aged 3 to 25 years with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (ALL). The FDA also is considering Kite Pharma’s application for axicabtagene ciloleucel (KTE-C19; axi-cel) as a treatment for transplant-ineligible patients with r/r non-Hodgkin lymphoma (NHL).

Just a handful of tertiary care centers would be able to provide CAR treatments in the beginning, making medical tourism a possibility, said Andre Goy, MD, MS, chairman, director, and Lymphoma Division chief at John Theurer Cancer Center (JTCC), Hackensack Meridian Health, in New Jersey. “Refractory lymphoma has no treatments, and when you have a technology that’s potentially serviceable for patients who are otherwise sent to hospice or die, people will come from very far away,” he said.

Estimates for treatment costs vary widely, from several hundred thousand dollars to as much as $700,000 per patient, oncology experts said in interviews. CAR T-cell engineering is a high-tech, labor-intensive process; it involves collecting the patient’s blood mononuclear cells, shipping them to a factory for refinement and enrichment ex vivo for T-cell growth, programming them with an anti-CD19 CAR transgene, testing, and finally returning those supercharged cancer-fighting cells to the clinical site where they can be reinfused into the patient. In the case of tisagenlecleucel, a separate clinical team is assigned to each blood shipment and follows it throughout the manufacturing process to ensure optimal quality and safety. All in all, manufacturing time for CAR T-cell therapies can stretch several weeks.

Estimates Reach $700,000

In addition to the costs of manufacturing the therapy, there are supportive care costs and potential expenses from additional lines of treatment, which may cause total medical costs to rise further.In the months leading up to potential FDA approvals, many stakeholders in this epic development in immunotherapy care have been unwilling to publicly discuss the bottom-line costs of care, although the issue reportedly has been foremost in negotiations and talks that had already begun to take place between medical institutions and payers. “We won’t be able to provide a live interview at this time, and any commercial/pay/cost questions won’t be addressed until the therapy is approved and launched,” said a spokeswoman for Novartis in response to a query from OncLive®. Novartis did provide written answers to questions about manufacturing specifics and offered to address other less-critical issues similarly.

Sensitivity to the cost issue extends to payers as well. Anthem, one of the largest healthcare companies with revenues of $85 billion in 2016, also declined to discuss CAR T-cell marketing. “CAR T-cell therapy has not yet been reviewed through the Anthem medical policy process,” the company said in a statement. “We anticipate developing a policy pending FDA approval. Anthem is committed to the ongoing evaluation of the safety and efficacy of therapeutic services to ensure clinically appropriate use based on clinical purposes.”

JTCC wants to be a part of the CAR T-cell launch and has been a testing site for the therapy that Kite Pharma pioneered. The center stands equally ready to help commercialize Novartis’ tisagenlecleucel and has been in talks with payers, according to Goy. He said payers are very concerned about where the price ceiling on this therapy is going to end up.

Goy said the point must be made in these discussions that a round of CAR T-cell therapy, although costly, might enable patients to avoid a lot of unsuccessful therapy that also builds up the medical tab for payers. “Yes, of course they’re nervous, but this is something that instead of giving therapies that don’t work, repeatedly, you can give something that gives a little mileage. Everything’s relative.”

Others support that argument by pointing out that there are no truly viable therapeutic alternatives to CAR T-cell therapy for patients with r/r ALL; therefore, they say the discussion should be about value to patients, not costs.

Andrew L. Pecora, MD, a famed bone marrow surgeon and chief innovations officer at Hackensack Meridian Health of New Jersey, said CAR T-cells could be dramatically more effective than bone marrow transplantation in the r/r ALL setting. But that won’t stop people from suffering a CAR T-cell—sized case of sticker shock, he predicted. He said common estimates are in the range of $250,000 to $500,000 for tisagenlecleucel, which is administered in a single-infusion dose.

Pecora said CAR T-cell therapies must prove their value over time, despite the early promise. “Soon, the warning bell will ring, and everyone will demand explanations for why these modified cells cost so much. Will this be another example of a high-flying technology that is overused and won’t add value to healthcare? I think not, but we must be cautious. The expense and complexity of this therapy demand that it work most of the time and replace another costly procedure—bone marrow transplantation,” Pecora said.

Pecora’s estimates of CAR T-cell costs are in the conservative range. The bottom end could be $300,000 and the top end $700,0000, before chemotherapy, emergency department, inpatient, and ICU care to manage adverse events, Swaminathan P. Iyer, MD, and Prakash Satwani, MD, told Targeted Therapies in OncologyTM magazine.

Dramatic Efficacy for Patients

Patients in whom these cells are infused will be at risk of severe reactions, such as cytokine release syndrome (CRS), but that is a sign the T cells are working. Iyer is a professor of medicine at the Institute for Academic Medicine, Houston Methodist Cancer Center, Weill Cornell Medical College in Houston, and Satwani is associate professor of pediatrics, Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, at New York-Presbyterian/Columbia University Medical Center in New York.The potential cost of CAR therapy seems like a lot of money, but what price should be attached to giving a child back his or her life? That’s the question that Gwen Nichols, MD, chief medical officer for the Leukemia & Lymphoma Society (LLS), poses. “The idea that a child who has failed standard therapy and has no other options could potentially have a remission with CAR T-cell therapy and be able to go back to a normal childhood is really priceless,” she said. “We need to figure out what these children would be getting if they weren’t getting this therapy, and that would be complex multichemotherapy regimens that would keep them in the hospital over long periods of time, or a bone marrow transplant, which is also an incredibly complex and costly procedure.”

The first available CAR T-cell treatment is expected to be tisagenlecleucel; the FDA is expected to make a decision under the Prescription Drug User Fee Act (PDUFA) deadline by the end of September. Novartis filed its biologics license application in March, based primarily on results from the ELIANA global CAR T-cell phase II study, in which the overall remission rate was 83% (95% CI, 71-91; P <.001) at 3 months following tisagenlecleucel infusion among patients with r/r ALL.1

The incidence of new cases of pediatric ALL is approximately 3100 in children and adolescents per year, and approximately 80%-85% of those cases are of B-cell origin. Current treatment for pediatric and young adult ALL includes chemotherapy, radiation therapy, and hematopoietic stem cell transplantation (HSCT). Relapses that occur within 18 months of initiation of therapy or while the patient is still on therapy have an extremely poor prognosis despite subsequent therapy. HSCT has been the only potential cure for relapse in recurrent pediatric ALL, but for it to succeed, there must be a complete response, preferably minimal-residual-disease negative.2

Under the standard of care, the chance of survival for children with ALL who relapse or fail to attain remission is between 16% and 30%.3

Kite Pharma is close behind, having completed its biologics license application for axicabtagene ciloleucel for patients with r/r aggressive NHL in March, based on findings from the ZUMA-1 trial. Axi-cel demonstrated an objective response rate of 82% and a complete response rate of 54% for patients with NHL.4 JTCC was one of the participating cancer centers. The FDA has granted a priority review to axicabtagene ciloleucel, with a PDUFA decision deadline of November 29.

Because of the complexity and dangers of CAR therapies, the FDA is expected to write any approval decision with very tight controls for where and under what conditions the therapy can be applied, Goy said. “The label is going to be very precise—maybe refractory disease or refractory to salvage therapy,” he predicted. Combination therapy likely won’t be allowed, at least in the beginning.

The FDA is expected to permit the therapy only in cancer centers that have participated in CAR T-cell trials and can manage severe reactions, Goy said. Hackensack Meridian Health, which late last year announced a major partnership with Memorial Sloan Kettering (MSK) Cancer Center of New York to extend immunotherapy and targeted therapy through research and collaborative clinical operations, is working with MSK to provide CAR T-cell treatment for up to 100 patients a year, Goy said.

The population of pediatric patients for whom CAR T-cell therapy would be available initially is relatively small, which means that the cost to provide it is not going to compete heavily with other disease categories for funds, Nichols said. She believes that money will be available to treat patients who need CAR T-cell therapy. The society is poised to help patients in any way it can through funding support and guidance.

In addition, payers already cover the standard of care for r/r ALL, including hospital stays, blood transfusions, heavy antibiotic use, and bone marrow transplants, all of which amount to tremendous costs that might be avoided with successful CAR T-cell therapy, Nichols said. “I think and I hope that payers will be looking at what the cost to them would be for not giving this treatment,”she said.

Making the Value Argument

Nichols identified a major barrier to access as being the shortage of cancer centers able to offer CAR T-cell therapy early on. “Only a few hospital centers have participated in the clinical trials and are prepared. How CAR T-cell therapy rolls out to major centers around the United States will pose an issue for patients trying to get to the centers,” she said. Conversely, although the restrictions on providing this therapy would be tight and only centers with experience in CAR T-cell trials would be authorized to provide this care, it would eventually be available to more locations and access would improve, Goy predicted.One of the dangers when any new-but-costly treatment enters mainstream medicine is that the focus is likely to gravitate to the expense of that single therapy, meaning that the broader debate on therapy costs and value may not receive its due. Nichols is hoping to expand the discussion on costs of care so that, in general, valuable treatments are not excluded based on price alone. “We’re hoping to continue to have discussions about how we can strategize together rather than pick this apart 1 agent at a time. I think that’s best for patients,” she said.

Part of the effort to prevent cost from becoming a prejudicial item in therapy selection is endeavoring to ensure that the right patients get the right treatment at the right time, Nichols said. She noted that toxicities associated with CAR T-cell therapies will be an important factor in the value equation when deciding who should receive these treatments. Patients who are advanced in age with frailties and comorbidities, for example, may not be ideal candidates, she said.

The value argument may become easier to make in the future. Researchers are working to bring toxicity potential under control, enabling more patients to benefit. The next generation of CAR T-cell treatments could include therapies that enable clinicians to switch off the T-cell reaction in the event CRS becomes too strong for a patient to withstand. “Second- and third-generation CAR T cells will have a different construct—cells that allow you to turn off the toxicity effect,” Goy said.

Bellicum Pharmaceuticals is developing an enzyme that could be engineered into CAR T cells and be used to kill them in the event of a severe reaction. Cellectis and Juno Therapeutics both have tested so-called suicide mechanisms for the same purpose—to shut down the T cells and bring CRS to an immediate halt. A spokesman for Juno said the company’s efforts to control the CRS effect now are focused more strongly on “precise dosing to maintain efficacy with low rates of severe CAR T-cell toxicities, thus avoiding the need for suicide mechanisms.” Late last year, Juno halted a phase II trial of a CAR T-cell agent following cerebral edema-related deaths. A pipeline Juno product utilizing the principle of defined dosing, JCAR017, has shown promise for r/r diffuse large B-cell lymphoma.

Goy envisions that, eventually, combination doses of CAR T cells and other small-molecule agents will be cleared for use. “For example, CAR T cells and ibrutinib in CLL seem to be much, much better than CAR T’s alone in CLL,” he said.

Bone marrow transplant is not likely to be offered as a combination treatment with CAR T cells, according to Pecora. In the r/r ALL setting, bone marrow transplant is far inferior to CAR T-cell treatment, he said.

Nichols said that a welcome innovation would be development of off-the-shelf CAR T-cell treatments that speed up the time leading up to infusion, because the patient’s own T cells would not be required. “That would reduce a lot of the issues with patients getting sick in between,” she said. “You could get it ready without having to do the harvesting procedure and the therapy beforehand.”


  1. Buechner J, Grupp SA, Maude SL, et al. Global registration trial of efficacy and safety of CTL019 in pediatric and young adult patients with relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL): update to the interim analysis. Presented at: 2017 EHA Congress; June 22-25, 2017; Madrid, Spain. Abstract S476.
  2. FDA. BLA 125646, Tisangenlecleucel, Novartis Pharmaceuticals Corporation. Silver Spring, MD. Oncologic Drugs Advisory Committee; July 2017. Briefing document. https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM566166.pdf.
  3. Novartis announces first CAR-T cell therapy BLA for pediatric and young adult patients with r/r B-cell ALL granted FDA priority review [press release]. Basel, Switzerland: Novartis; March 29, 2017. novartis.com/news/media-releases/novartis-announces-first-car-t-cell-therapy-bla-pediatric-and-young-adult. Accessed August 2, 2017.
  4. Locke FL, Neelapu SS, Bartlett NL, et al. Primary results from ZUMA-1: a pivotal trial of axicabtagene ciloleucel (axi-cel; KTE-C19) in patients with refractory aggressive non-Hodgkin lymphoma (NHL). Presented at: 2017 AACR Annual Meeting; April 1-5, 2017; Washington, DC. Abstract CT019.