MEDCAC Panel Mostly Endorses PROs for CAR T Therapies

How should CMS incorporate patient-reported outcomes (PROs), if at all, in any future decisions it makes about clinical studies and coverage of chimeric antigen receptor (CAR) T-cell therapy for Medicare beneficiaries with advanced leukemias and lymphomas? During a meeting of the Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) on August 22, panelists heard from CAR T therapy drug makers, health researchers, and policy makers, and then voted their degree of confidence on the issue of including PROs in this fast-moving issue.

Presentations before the panel reviewed trial data on existing CAR T treatments and the PROs under consideration, and discussed clinical study design characteristics, study duration, and suitable study controls.

Some companies, including Novartis, said they would like the national coverage analysis (NCA) period, which CMS opened in May, withdrawn. Cori Abikoff, MD, medical director for Novartis' CAR T program, said during her presentation that an NCA may keep beneficiaries from accessing the game-changing immunotherapy for hematologic cancers.

Novartis’ product, tisagenlecleucel (Kymriah)—a treatment for children and young adults with B-cell acute lymphoblastic leukemia—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.

CMS approved extra payments for CAR T therapies in new rule.

Abikoff said an NCA may lead Medicare administrative contractors and other payers that are currently covering therapy to withhold coverage until next year’s conclusion of the NCA, which was requested by UnitedHealthcare and is supported by payers, as well as America’s Health Insurance Plans. There are concerns that an NCA could limit access issues for the sickest patients. There are also concerns that mandatory PROs—outside of randomized control trials—are burdensome on healthcare providers and patients.

William Go, MD, PhD, vice president of clinical development at Kite, said PROs are “not quite ready for real-world coverage decisions.”

Others in the drug industry were opposed as well, including the Pharmaceutical Research and Manufacturers of America, known as PhRMA, as well as BIO, a biotechnology trade organization.

The wide-ranging panel discussion and questions of presenters focused on what patients need and want to hear from their doctors in the face of a life threatening disease.

“People like to know what to expect,” said Ethan Basch, MD, MSc, a professor of health policy and management and director of the Cancer Outcomes Research Program at the UNC Lineberger Comprehensive Cancer Center at the University of North Carolina.

Before the panel voted, Basch presented about the applicability of PROs to CAR T, discussing symptomatic adverse events, short-term toxicity, long-term toxicity, early warning signs of life-threatening cytokine release syndrome, physical functioning, and changes in disease-related symptoms.

For instance, “if my patient is lying in bed all day, I’d like to know about it,” said Basch, a hematologist oncologist.

PRO data, while valued, can also be difficult to understand by both patients and providers, said another presenter, Claire Snyder, PhD, a professor of medicine, oncology, and health policy and management at the Johns Hopkins Schools of Medicine and Public Health. It is highly variable and can be challenging to interpret. There is no standardization in how they are scaled, scored, or how they are presented, said Snyder.

“The field is in motion,” said Thomas F. Goss, PharmD, senior vice president, Boston Healthcare Associates, who sought clarification from CMS staff on if the 5 questions they were voting on, and related subquestions (23 total), are CAR-T specific. They are not, the panel was told.

Each member voted individually and the votes were averaged, answering most questions on a scale of 1 to 5 (some were yes/no) with 1 being low confidence and 5 being high confidence. No PRO has been used to drive a negative decision, the panel was told.

Panel members seemed interested in seeing the further development of PROs, but also also urged caution. They also wanted to make sure that patient concerns about CAR T therapies were heeded.

“Always focus on the patient as an individual rather than a population,” said patient and consumer advocate Naftali Z. Frankel, MS.

CMS is not required to take the advice of the panel under consideration and the PRO piece is just one it will consider when it wraps up its work on the NCA next year.