CMS Advisers Back Patient Reporting Tools for CAR-T Drugs

Kerry Dooley Young

August 23, 2018

A big question looming over chimeric antigen receptor T-cell (CAR-T) therapy is how to meet the huge cost of this novel treatment.

The Centers for Medicare & Medicaid Services (CMS) is currently in the midst of its analysis regarding a potential national coverage decision for these products.

As part of this process, CMS asked its Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) to consider seven approaches for collecting data on patients' experiences with these drugs. At a meeting on 22 August, the panel backed four of the patient-reported outcome (PRO) tools presented by CMS, while giving lower marks to another three.

Currently, there are two CAR-T products on the US market — tisagenlecleucel (Kymriah, Novartis) and axicabtagene ciloleucel (Yescarta, Gilead Sciences' Kite Pharma).

Government and commercial insurers are concerned about how CAR-T drugs will affect their budgets as use of these new medicines become more common.

The products themselves come with price tags of about $400,000, but ancillary costs of treatment may run past $33,000 per patient according to media reports, noted Peter Bach, MD, from Memorial Sloan Kettering Cancer Center, New York City, in an article published online August 15 in the in the New England Journal of Medicine.

Industry Opposes Use of These Tools

At the meeting, CMS did not directly ask the panel whether the agency should incorporate this kind of feedback into its payment decisions for CAR-T.

Still, the panelists' support for these tools seemed to run contrary to the arguments made by representatives from the companies that are marketing these products.

William Go, MD, PhD, vice president for clinical development at Gilead's Kite unit, argued that adding new demands for patients' reports could interfere with attempts to enroll people dying of cancer into trials and jeopardize their chances for success.

Patients selected for CAR-T often are considered to have less than 6 months to live and may be at a stage where their physicians would be discussing hospice options with them, he said. Yet, CAR-T therapy takes more time to prepare than traditional medicines, because patients have to undergo a procedure to collect blood samples that are then sent to a Gilead facility to have the patients' T cells re-engineered to fight their cancer.

"This turnaround process of a patient's own truly personalized medicine is approximately 17 days from door to door," Go told the panel. "Every day matters for these patients."

Go and other scientists representing drugmakers stressed to MEDCAC that the CAR-T drugs are administered at selected hospitals, where the staff has experience in managing severe toxicities. The US Food and Drug Administration (FDA) has already put in place risk evaluation and mitigation strategies for these drugs.

Company representatives also spoke about their current efforts to gather information from patients about their symptoms and well-being, but they argued that these data aren't yet packaged in a form suitable for payment considerations.

"We feel PROs are not quite ready for real-world coverage decisions at this time," Go said.

Cori Abikoff, MD, the medical director for CAR-T drugs at Novartis Oncology, urged CMS to scrap its current examination of Medicare's approach to paying for these medicines.

She said that the current national coverage analysis "is inconsistent with past CMS policy, unnecessary, not practical, an administrative burden on providers, and will impact beneficiary access to CAR-T therapy."

Some of Medicare's administrative contractors might withhold coverage of these drugs until the scheduled conclusion in May 2019, she said, which would mean that some patients who could be suitable for this treatment would not have the chance to try it.

Abikoff urged CMS to withdraw its national coverage analysis for CAR-T products.

In closing the meeting, Tamara Syrek Jensen, JD, the director of CMS' Coverage and Analysis Group, said the agency would take into consideration the full discussion from the meeting, but also reaffirmed plans to release a preliminary decision on the CAR-T drugs in February 2019.

CMS asked the MEDCAC panelists to vote on seven tools used to gather patients' reports, posing this question: "How confident are you that each of the following PRO assessments are valid and generalizable to the Medicare population?"

CMS asked the panelists to use a scale in which a score of 1 represented low or no confidence and 5 represented high confidence. CMS then considered for further discussion and evaluation the tests that received initial scores of greater than 2.5.

In the voting, the top mark went to the Patient-Reported Outcome Measurement Information System (PROMIS), which is a National Institutes of Health (NIH)–funded initiative. The NIH describes PROMIS as a means to "enhance and standardize measurement of several selected PROs through both computer adaptive testing and traditional 'paper and pencil' instruments." It had an overall average score of 4.15.

Other tools with scores adequate to warrant for further discussion were as follows:

  • The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC—QLQ-C30 ), which is a "stand-alone multidimensional questionnaire covering issues important for all cancer patients," according to CMS. It had an average score of 4.00.

  • The Patient-Reported Outcomes–Common Terminology Criteria for Adverse Events (PRO-CTCAE). This tool was developed in 2008 to supply meaningful data and improve understanding of symptomatic adverse events from multiple disease states. It had an average score of 3.54.

  • MD Anderson Symptom Inventory (MDASI). CMS said this tool, developed in 2000, appears to be equally effective in its paper, electronic, and telephone-based formats in terms of both clinical trial workflow and user experience. It had an average score of 3.46.

Three tests fell short of the 2.5 mark. They were the University of Washington Quality of Life (UW-QOL), which had an average score of 1.62; the Electronic Self-Report–Cancer (ESRA-C), which had an average score of 1.54; and the Functional Living Index–Cancer (FLIC), with a 1.38 average score.

Physicians have many decades of experience in collecting patient-reported outcomes as part of clinical trials, said Ethan Basch, MD, of the Lineberger Comprehensive Cancer Center at University of North Carolina at Chapel Hill. He spoke about the field of PROs during a scheduled presentation at the MEDCAC meeting and several times offered responses to comments from the company representatives during the discussion.

In Basch's view, the concerns cited about potential administrative burden from PROs seemed "rather absurd."

"There are all different kinds of ways it can be done. It can be done on paper. It can be done with a telephone survey system. It can be done with an iPhone or an Android system," Basch said. "This is done all the time. There are hundreds and hundreds and hundreds of registries in oncology patient populations with 90-plus percent compliance rates."

CMS's decision to convene the MedCAC panel is part of its continuing effort to understand how treatments affect patients' lives, rather than simply relying on clinical indicators, such as X-ray readings, commented Louis Jacques, MD, chief clinical officer of the healthcare advisory firm ADVI. He was director of CMS' Coverage and Analysis Group from 2009 to 2014, and he attended the meeting as an observer.

"This is very important, especially as we see new therapies that obtain regulatory approval with relatively small datasets developed over a short term," Jacques told Medscape Medical News in an interview after the meeting.

The FDA has been working to speed approval of new cancer medicines in recent years. In 2017, the agency cited the results for tisagenlecleucel in one clinical trial of 63 pediatric and young adult patients in announcing its approval of the drug for acute lymphoblastic leukemia. In 2018, the FDA approved the drugs for adult patients with relapsed or refractory large B-cell lymphoma, citing results seen in a pool of 68 evaluable patients.

Ongoing Analysis

The MEDAC is part of an ongoing analysis being undertaken by the CMS for a potential national coverage decision for CAR-T products. The process began in May 2018 in response to a request from insurance giant UnitedHealth Group (one of the largest operators of insurer-run Medicare Advantage plans.)

In a February 22, 2018, letter to CMS, Efrem Castillo, MD, the chief medical officer for Medicare and retirement issues at UnitedHealth, noted that CAR-T drugs have known potential for severe and life-threatening side effects, and thus specialized expertise is required to manage treatment.

"Given the new CAR-T therapies in the pipeline — which are also promising clinically but very expensive — we believe there is an opportunity to address national, consistent and thoughtful coverage criterion for Medicare beneficiaries to maximize the benefit of these new therapies," Castillo wrote.

Dr Basch has received funding from the National Cancer Institute and the Patient-Centered Outcomes Research Institute for research on PROs. He has also been a consultant to RTI on CMS ' Oncology Care Model and an advisor to Noona Healthcare.

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