Many Questions to Ask in Setting National Coverage for CAR T Therapies

Next week, a CMS committee will hold a daylong meeting to discuss a national coverage determination (NCD) for chimeric antigen receptor (CAR) T-cell immunotherapies, the game-changing cancer treatment approved by the FDA for 2 indications, and being studied for more.

The request for an NCD was put forth by UnitedHealthcare, the nation's largest insurer and also the largest provider of Medicare Advantage plans. With a 1-time treatment costing more than $400,000 and unpredictable related hospital stays and treatment for complications, payers are watching this issue with intense interest, especially if the patient pool expands.

In New England Journal of Medicine, Peter B. Bach, MD, MAPP, reviewed several strategies open to CMS as it continues to try to determine how to pay for CAR T, the costliest cancer treatment invented to date.¹

Tisagenlecleucel (Kymriah)—a treatment for children and young adults with B-cell acute lymphoblastic leukemia developed by Novartis—is priced at about $475,000 for a 1-time treatment. Axicabtagene ciloleucel (Yescarta)—Kite Pharma/Gilead’s treatment for adult patients with relapsed or refractory large B-cell lymphoma—is priced at $373,000.

Read a CAR T-Cell Therapy Update from ASCO 2018 in Evidence-Based Oncology.

On Wednesday, August 22, the Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) will review the evidence specific to patient reported outcomes (PROs) as it relates to CAR T.

In his Perspective column, Bach, director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center, noted that the treatments are not without risk, and that the treatment for severe complications, such as cytokine release syndrome (CRS), can cost upwards of $33,000 per patient.

A July report estimated that with 600 patients eligible for tisagenlecleucel every year in the United States, annual expenditures would cost $259 million. For axicabtagene ciloleucel, which has a larger potential pool of 7500 adults, total expenditures would be more than $3 billion.²

CMS is required to cover services that are “reasonable and necessary” to treat illnesses. The agency does not consider price, but as healthcare costs have increased, it has started to ask more questions about the evidence of treatments, Bach noted.

CAR T is not like conventional cancer therapy. Created from a patient’s own genetically modified T-cells that are engineered to express receptors that latch on to a specific cell surface protein, the cells connect to cancer cells and destroy them. Treatments for individual patients take weeks to create.

And unlike other conventional cancer drugs, the therapies were approved after the outcome of small, uncontrolled studies, Bach wrote. Axicabtagene ciloleucel produced complete remission in 51 out of 101 patients with non-Hodgkin lymphoma. Tisagenlecleucel produced complete responses in 32% of patients.

CMS will have to decide whether it has “adequate confidence” on 2 points, Bach said: whether the net benefits of the CAR T therapies are similar, and whether the ancillary services that go along with the treatments have similar costs. The answers to those questions could determine how CMS proceeds.

If the net benefit is similar, CMS could promote price competition, but how it does that depends on whether one is also confident in the similarity of any related costs. Looking at CAR T therapy alone, CMS could use a process similar to competitive bidding or competitive acquisition, already used by the agency in other areas.

If it is uncertain about ancillary costs, such as stays in an intensive care unit related to complications, CMS could move those to a bundled payment system. For instance, CRS can vary from high fevers for a few days to hypotension, multiorgan failure, and death. Other possibilities include confusion, lethargy, stroke-like symptoms, and coma.

On the other hand, Bach said that CMS may also lack confidence that the therapies have similar net benefits. In that case, coverage could be limited to patients enrolled in randomized clinical trials.

Novartis was originally pursuing a value-based outcomes agreement with CMS, but that agreement apparently fell apart after a scandal involving President Donald Trump’s former attorney became public.

In an earlier column in JAMA last year, Bach and other authors noted that another approach Novartis could take in the future is to pursue “indication-specific” pricing, meaning tisagenlecleucel could have multiple prices, depending on which cancer it is treating. Efficacy could be lower, but market size could be larger, depending on the indication.³

Earlier this month, CMS approved add-on payments estimated to cost about $72 million for CAR T, agreeing to pay a maximum of $186,500 per case, starting in fiscal year 2019, based on 373 patients. In addition, it will assign inpatient cases involving CAR T treatments to a higher-weighted Medicare-severity diagnosis related group (DRG) related to bone marrow transplants.

1. Bach PB. National coverage analysis of CAR T therapies — policy, evidence, and payment. [published online August 16, 2016]. NEJM. doi:10.1056/NEJMp1807382.

2. Hernandez I, Prasad V, Gellad WF. Total costs of chimeric antigen receptor t-cell immunotherapy. JAMA Oncol. 2018;4(7):994-996. doi:10.1001/jamaoncol.2018.0977.

3. Bach PB, Giralt SA, Saltz LB. FDA approval of tisagenlecleucel-promise and complexities of a $475,000 cancer drug. JAMA. 2017;318(19):1861-1862. doi:10.1001/jama.2017.15218.

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